I. Genetics And BehaviorP. L. Broadhurst
II. Demography and Population GeneticsJean Sutter
III. Race and GeneticsJ. N. Spuhler
Behavior genetics is a relatively new cross-disciplinary specialization between genetics and Psychology. It is so new that it hardly knows what to call itself. The term “behavior genetics” is gaining currency in the United States; but in some quarters there, and certainly elsewhere, the term “psycho-genetics” is favored. Logically, the best name would be genetical psychology, since the emphasis is on the use of the techniques of genetics in the analysis of behavior rather than vice versa; but the in evitable ambiguity of that term is apparent. Psy chologists generally use the terms “genetic” or “genetical” in two senses: in the first and older sense of developmental, or ontogenetic; and in the second, more recent usage relating to the analysis of inheritance. The psychologist G. Stanley Hall coined the term “genetic” before the turn of the century to denote developmental studies (witness the Journal of Genetic Psychology), and Alfred Binet even used the term “psychogenetic” in this sense. But with the rapid rise of the discipline now known as genetics after the rediscovery of the Mendelian laws in 1900, William Bateson, one of the founders of this new science, pre-empted the term “genetic” in naming it, thereby investing “genetic” with the double meaning that causes the current confusion. Psychological genetics, with its obvious abbreviation, psychogenetics, is probably the best escape from the dilemma.
Importance of genetics in behavior. The importance of psychogenetics lies in the fundamental nature of the biological processes in our understanding of human social behavior. The social sciences, and psychology in particular, have long concentrated on environmental determinants of behavior and neglected hereditary ones. But it is clear that in many psychological functions a substantial portion of the observed variation, roughly of the order of 50 per cent for many traits, can be ascribed to hereditary causation. To ignore this hereditary contribution is to impede both action and thought in this area.
This manifold contribution to behavioral variation is not a static affair. Heredity and environment interact, and behavior is the product, rather than the sum, of their respective contributions. The number of sources of variability in both he redity and environment is large, and the consequent number of such possible products even larger. Nevertheless, these outcomes are not incalculable, and experimental and other analyses of their limits are of immense potential interest to the behavioral scientist. The chief theoretical interest lies in the analysis of the evolution of behavior; and the chief practical significance, so far as can be envisaged at present, lies in the possibilities psychogenetics has for the optimization of genetic potential by manipulation of the environmental expression of it.
Major current approaches. The major approaches to the study of psychogenetics can be characterized as the direct, or experimental, and the indirect, or observational. The former derive principally from the genetical parent of this hybrid discipline and involve the manipulation of the heredity of experimental subjects, usually by restricting the choice of mates in some specially defined way. Since such techniques are not possible with human subjects a second major approach exists, the indirect or observational, with its techniques derived largely from psychology and sociology. The two approaches are largely complementary in the case of “natural” genetic experiments in human populations, such as twinning or cousin marriages. Thus, the distinction between the two is based on the practicability of controlling in some way the essentially immutable genetic endowment—in a word, the genotype—of the individuals subject to investigation. With typical experimental animals (rats, mice, etc.) and other organisms used by the geneticist, such as the fruit fly and many microorganisms, the genotype can often be specified in advance and populations constructed by the hybridization of suitable strains to meet this specification with a high degree of accuracy. Not so with humans, where the genotype must remain as given, and indeed where its details can rarely be specified with any degree of accuracy except for certain physical characteristics, such as blood groups. Observational, demographic, and similar techniques are therefore all that are available here. The human field has another disadvantage in rigorous psychogenetic work: the impossibility of radically manipulating the environment—for example, by rearing humans in experimental environ ments from birth in the way that can easily be done with animals in the laboratory. Since in psychogenetics, as in all branches of genetics, one deals with a phenotype—in this case, behavior— and since the phenotype is the end product of the action, or better still, interaction of genotype and environment, human psychogenetics is fraught with double difficulty. Analytical techniques to be mentioned later can assist in resolving some of these difficulties.
Definition. To define psychogenetics as the study of the inheritance of behavior is to adopt a misleadingly narrow definition of the area of study, and one which is unduly restrictive in its emphasis on the hereditarian point of view. Just as the parent discipline of genetics is the analysis not only of the similarities between individuals but also of the differences between them, so psychogenetics seeks to understand the basis of individual differences in behavior. Any psychogenetic analysis must therefore be concerned with the environmental determinants of behavior (conventionally implicated in the genesis of differences) in addition to the hereditary ones (the classic source of resemblances). But manifestly this dichotomy does not always operate, so that for this reason alone the analysis of environmental effects must go hand in hand with the search for genetic causation. This is true even if the intention is merely to exclude the influence of the one the better to study the other; but the approach advocated here is to study the two in tandem, as it were, and to determine the extent to which the one interacts with the other. Psychogenetics is best viewed as that specialization which concerns itself with the interaction of heredity and environment, insofar as they affect behavior. To attempt greater precision is to become involved in subtle semantic problems about the meanings of terms.
At first sight many would tend to restrict environmental effects to those operating after the birth of the organism, but to do so would be to exclude prenatal environmental effects that have been shown to be influential in later behavior. On the other hand, to broaden the concept of environment to include all influences after fertilization— the point in time at which the genotype is fixed —permits consideration of the reciprocal influence of parts of the genotype upon each other. Can environment include the rest of the genotype, other than that part which is more or less directly concerned with the phenotype under consideration? This point assumes some importance since there are characteristics, not behavioral—at least, none that are behavioral have so far been reported— whose expression depends on the nature of the other genes present in the organism. In the absence of some of them, or rather certain alleles of the gene pairs, the value phenotypically observed would be different from what it would be if they were present. That is, different components of the genotype, in interplay with one another, modify phenotypic expression of the characteristic they in fluence. Can such indirect action, which recalls that of a chemical catalyst, best be considered as environmental or innate? It would be preferable to many to regard this mechanism as a genetic effect rather than an environmental one in the usually accepted sense. Hence, the definition of the area of study as one involving the interaction of heredity and environment, while apparently adding complexity, in fact serves to reduce confusion.
It must be conceded that this view has not as yet gained general acceptance. In some of the work reviewed in the necessarily brief survey of the major findings in this area, attempts have been made to retain a rather rigid dichotomy between heredity and environment—nature versus nurture —in fact, an “either/or” proposition that the facts do not warrant. The excesses of both sides in the controversies of the 1920s—for example, the famous debate between Watson and McDougall over the relative importance of learned (environmental) and instinctive (genetic) determinants of behavior —show the fallacies that extreme protagonists on either side can entertain if the importance of the interaction effect is ignored.
Gene action. The nature of gene action as such is essentially conducive to interaction with the environment, since the behavioral phenotype we observe is the end product of a long chain of action, principally biochemical, originating in the chromosome within the individual cell. A chromosome has a complex structure, involving DNA (deoxyribonucleic acid) and the connections of DNA with various proteins, and may be influenced in turn by another nucleic acid, RNA (ribonucleic acid), also within the cell but external to the nucleus. There are complex structures and sequences of processes, anatomical, physiological, and hormonal, which underlie normal development and differentiation of structure and function in the growth, development, and maturation of the organism. Much of this influence is determined genetically in the sense that the genotype of the organism, fixed at conception, determines how it proceeds under normal environmental circumstances. But it would be a mistake to regard any such sequence as rigid or immutable, as we shall see.
The state of affairs that arises when a number of genetically determined biochemical abnormalities affect behavior is illustrative of the argument. Many of these biochemical deficiencies or inborn errors of metabolism in humans are the outcome of a chain of causation starting with genie structures, some of them having known chromosomal locations. Their effects on the total personality—that is, the sum total of behavorial variation that makes the individual unique—can range from the trivial to the intense. The facility with which people can taste a solution of phenylthiocarbamide (PTC), a synthetic substance not found in nature, varies in a relatively simple genetical way: people are either “tasters” or “nontasters” in certain rather well-defined proportions, with a pattern of inheritance determined probably by one gene of major effect. But being “taste blind” or not is a relatively unimportant piece of behavior, since one is never likely to encounter it outside a genetical experiment. (It should perhaps be added that there is some evidence that the ability to taste PTC may be linked with other characteristics of some importance, such as susceptibility to thyroid disease.) Nevertheless, this example is insignificant compared with the psychological effect of the absence of a biochemical link in patients suffering from phenylketonuria. They are unable to metabolize phenylalanine to tyrosine in the liver, with the result that the phenylalanine accumulates and the patient suffers multiple defects, among which is usually gross intellectual defect, with an IQ typically on the order of 30. This gross biochemical failure is mediated by a single recessive gene that may be passed on in a family unnoticed in heterozygous—single dose—form but becomes painfully apparent in the unfortunate individual who happens to receive a double dose and consequently is homozygous for the defect.
Alternatively, a normal dominant gene may mutate to the recessive form and so give rise to the trouble. While mutation is a relatively rare event individually, the number of genes in each individual—probably on the order of ten thousand —and the number of individuals in a population make it statistically a factor to be reckoned with. One of the best documented cases of a deleterious mutation of this kind giving rise to a major defect relates to the hemophilia transmitted, with certain important political consequences, to some of the descendants of Queen Victoria of England. The dependence of the last tsarina of Russia on the monk Rasputin was said to be based in part on the beneficial therapeutic effect of his hypnotic techniques on the uncontrollable bleeding of the Tsarevitch Alexis. Victoria was almost certainly heterozygous for hemophilia and, in view of the absence of any previous record of the defect in the Hanoverian dynasty, it seems likely that the origin of the trouble was a mutation in one of the germ cells in a testicle of Victoria’s father, the duke of Kent, before Victoria was conceived in August 1818.
But however it comes about, a defect such as phenylketonuria can be crippling. Fortunately, its presence can be diagnosed in very early life by a simple urine test for phenyl derivatives. The dependence of the expression of the genetic defect on the environmental circumstances is such that its effect can be mitigated by feeding the afflicted infant with a specially composed diet low in the phenylalanine with which the patient’s biochemical make-up cannot cope. Here again, therefore, one sees the interaction of genotype and environment —in this case the type of food eaten. Many of the human biochemical defects that have been brought to light in recent years are rather simply determined genetically, in contrast with the prevailing beliefs about the bases of many behavioral characteristics including intelligence, personality, and most psychotic and neurotic disorders. This is also true of several chromosomal aberrations that have been much studied recently and that are now known to be implicated in various conditions of profound behavioral importance. Prominent among these is Down’s syndrome (mongolism) with, again, effects including impairment of cognitive power. [SeeIntelligence and Intelligence Testing; Mental Disorders, articles onBiological AspectsandGenetic Aspects.]
Sex as a genetic characteristic. The sex difference is perhaps the most striking genetically determined difference in behavior and the one that is most often ignored in this connection. Primary sex is completely determined genetically at the moment of fertilization of the ovum; in mammals sex depends on whether the spermatozoon effecting fertilization bears an X or a Y chromosome to combine with the X chromosome inevitably contributed by the ovum. The resulting gamete then has the form of an XX (female) or an XY (male) individual. This difference penetrates every cell of every tissue of the resulting individual and in turn is responsible for the observable gross differences in morphology. These, in turn, subserve differences of physiological function, metabolism, and endocrine function which profoundly influence not only those aspects of behavior relating to sexual behav ior and reproductive function in the two sexes but many other aspects as well. But behavior is also influenced by social and cultural pressures, so that the resulting sex differences in behavior as observed by the psychologist are especially good examples of a phenotype that must be the and product of both genetic and environmental forces. There is a large literature on sex differences in human behavior and a sizable one on such differ ences in animal behavior, but there has been little attempt to assess this pervasive variation in terms of the relative contribution of genetic and environmental determinants. This is partly because of the technical difficulties of the problem, in the sense that all subjects must be of either one sex or the other—crossing males with females will always result in the same groups as those one started with, either males or females—there being, in general, no genetically intermediate sex against which to evaluate either and identical twins being inevitably of like sex. It is also partly because the potential of genetic analyses that do not involve direct experi mentation has not been realized. This is especially so since the causal routes whereby genetic determinants of sex influence many of the behavioral phenotypes observed are often better understood than in other cases where the genetic determinants underlying individual differences manifest in a population are not so clear-cut. [SeeIndividualDifferences, article onSex Differences.]
Sex linkage. There is one exception to the general lack of interest in the biometrical analysis of sex differences having behavioral connotations: sex-linked conditions. That is to say, it is demonstrated or postulated that the gene or genes responsible for the behavior—often a defect, as in the case of color blindness, which has a significantly greater incidence in males than in females—are linked with the sex difference by virtue of their location on the sex chromosome determining genetic sex. Thus it is that sex can be thought of as a chromosomal difference of regular occurrence, as opposed to aberrations of the sort which give rise to pathological conditions, such as Down’s syndrome. Indeed there are also various anomalies of genetic sex that give rise to problems of sexual identity, in which the psychological and overt be havioral consequences can be of major importance for the individual. While the evidence in such cases of environmental modification of the causative genetic conditions is less dramatic than in phenylketonuria, interaction undoubtedly exists, since these chromosomal defects of sex differentiation can in some cases be alleviated by appropriate surgical and hormonal treatment. [SeeSexual BEHavior, article onSexual Deviation: Psychological Aspects; andVision, article onColor Vision and Color Blindness.]
Human psychogenetics. It is abundantly clear that most of the phenotypes the behavioral scientist is interested in are multidetermined, both environmentally and genetically. The previous examples, however, are the exception rather than the rule, and their prominence bears witness that our understanding of genetics and behavior is as yet so little advanced that the simpler modes of genetic expression have been the first to be explored. In genetics itself, the striking differences in seed configuration used by Mendel in his classic crosses of sweet peas are determined by major genes with full dominance acting simply. But such clear-cut expression, especially of dominance, is unusual in human psychogenetics, and more complex statistical techniques are necessary to evaluate multiple genetic and environmental effects acting to produce the observed phenotype.
Whatever the analysis applied to the data gathered in other fields, in human psychogenetics the method employed cannot be the straightforward Mendelian one of crossbreeding which, in various elaborations, remains the basic tool of the geneticist today. Neither can it be the method of selection —artificial, as opposed to natural—that is other wise known as selective breeding. Indeed, none of the experimental techniques that can be applied to any other organism, whatever the phenotype being measured, is applicable to man, since experimental mating is effectively ruled out as a permissible technique in current cultures. It may be remarked in passing that such has not always been the case. The experiment of the Mogul emperor, Akbar, who reared children in isolation to determine their “natural religion” (and merely produced mutes) and the eugenics program of J. H. Noyes at the Oneida Community in New York State in the nineteenth century are cases in point. The apparent inbreeding of brother with sister among the rulers of ancient Egypt in the eighteenth dynasty (sixteenth to fourteenth century B.C.), which is often quoted as an example of the absence in humans of the deleterious effects of inbreeding (“inbreeding depression”), may not be all it seems. It is likely that the definition of “sister” and “brother” in this context did not necessarily have the same biological relevance that it has today but was rather a cultural role that could be defined, at least in this case, at will.
Twin study. In the absence of the possibility of an experimental approach, contemporary re search in human psychogenetics must rely on natural genetic experiments. Of these, the one most widely used and most industriously studied is the phenomenon of human twinning. Credit for the recognition of the value of observations on twins can be given to the nineteenth-century English scientist entist Francis Galton, who pioneered many fields of inquiry. He may be justly regarded as the father of psychogenetics for the practical methods he introduced into this field, such as the method of twin study, as well as for his influence which extended, although indirectly, even to the American experimenters in psychogenetics during the early decades of the present century.
Twin births are relatively rare in humans and vary in frequency with the ethnic group. However, the extent to which such ethnic groups differ among themselves behaviorally as a result of the undoubted genetic differences, of which incidence of multiple births is but one example, is controversial. As is well known, there are two types of twins: the monozygotic or so-called identical twins, derived from a single fertilized ovum that has split into two at an early stage in development, and the dizygotic or so-called fraternal twins, developed from two separate ova fertilized by different spermatozoa. These two physical types are not always easy to differentiate, although this difficulty is relatively miner in twin study. Nonetheless, they have led to two kinds of investigation. The first relates to differences in monozygotic twins who have identical hereditary make-up but who have been reared apart and thus subjected to different environmental influences during childhood; and the second relates to the comparison of the two types of twins— usually restricted to like-sex pairs, since fraternal twins can differ in sex. The latter method supposes all differences between monozygotic pairs to be due to environmental origin, whereas the (greater) difference between dizygotic pairs is of environmental plus genetic origin. Thus, the relative contribution of the two sources of variation can be evaluated.
Findings obtained from either method have not been especially clear-cut, both because of intractable problems regarding the relative weight to be placed upon differences in the environment in which the twins have been reared and because of the sampling difficulties, which are likely to be formidable in any twin study. Nevertheless, interesting inferences can be drawn from twin study. The investigation of separated monozygotic twins has shown that while even with their identical heredity they can differ quite widely, there exists a significant resemblance in basic aspects of personality including intelligence, introversion, and neurotic tendencies, and that these resemblances can persist despite widely different environments in which the members of a pair are reared. Such findings emphasize the need to consider the contribution of genotype and environment in an inter active sense—clearly some genotypes represented in the personality of monozygotic twin pairs are sensitive to environmentally induced variation, whereas others are resistant to it.
Comparisons between monozygotic and dizygotic twins reared together suggest that monozygotic twins more closely resemble each other in many aspects of personality, especially those defining psychological factors such as neuroticism and introversion-extroversion. The increase in the differences between the two types of twins when factor measures are used—as opposed to simple test scores—suggests that a more basic biological stratum is tapped by factor techniques, since the genetic determination seems greater than where individual tests are employed. Here again, the de gree to which any phenotype is shown to be hereditary in origin is valid only for the environment in which it developed and is measured; different environments may well yield different results. The problems of environmental control in human samples are so intractable that some students of the subject have questioned whether the effort and undoubted skill devoted to twin study have been well invested, in view of the inherent and persisting equivocality of the outcome.
Multivariate methods. Methods of twin study, introduced largely to improve upon the earlier methods of familial correlation (parents with off spring, sib with sib, etc.), have been combined with them. Familial correlation methods them selves have not been dealt with here, since within-family environments are bound to be even greater contaminants in determining the observed behavior than environments in twin study methods. Never theless, used on a large scale and in conjunction with twin study and with control subjects selected at random from a population, multivariate methods show promise for defining the limits of environmental and genotypic interaction. So far, the solutions to the problems of biometrical analysis posed by this type of investigation have been only partial, and the sheer weight of effort involved in locating and testing the requisite numbers of subjects standing in the required relationships has deterred all but a few pioneers. Despite the undoubtedly useful part such investigations have played in defining the problems involved, the absence of the possibility of experimental breeding has proved a drawback in the provision of socially useful data.
Animal psychogenetics. Recourse has often been had to nonhuman subjects. The additional problem thereby incurred of the relevance of comparative data to human behavior is probably balanced by the double refinements of the control of both the heredity and the environment of the experimental subjects. Two major methods of genetics have been employed, both intended to produce subjects of predetermined genotype: the crossbreeding of strains of animals of known genotype; and phenotypic selection, the mating of like with like to increase a given characteristic in a population.
Selection. Behavioral phenotypes of interest have been studied by the above methods, often using laboratory rodents. For example, attributes such as intelligence, activity, speed of conditioning, and emotionality have been selectively bred in rats.
Selection for emotional behavior in the rat will serve as an example of the techniques used and the results achieved. Rats, in common with many other mammalian species, defecate when afraid. A technique of measuring individual differences in emotional arousal is based on this propensity. The animal under test is exposed to mildly stressful noise and light stimulation in an open field or arena. The number of fecal pellets deposited serves as an index of disturbance, and in this way the extremes among a large group of rats can be characterized as high or low in emotional responsiveness. Continued selection from within the “high” and “low” groups will in time produce two distinct strains. Control of environmental variables is achieved by a rigid standardization of the conditions under which the animals are reared before being subjected to the test as adults. Careful checks on maternal effects, both prenatal and postnatal, reveal these effects to be minimal.
Such an experiment does little beyond establishing the importance of the genetic effect on the given strains in the given environment. While there are techniques for assessing the relative importance of the genetic and environmental contributions to the variation observed under selection, they are better suited to the analysis of the outcome of experiments using the alternative major genetical method, that of crossbreeding of inbred strains.
Crossbreeding. Strains used in crossbreeding experiments have usually been inbred for a phenotypic character of interest, although not usually a behavioral one. However, this does not preclude the use of these inbred strains for behavioral studies, since linkage relationships among genes ensure that selection for factors multidetermined genetically often involves multiple changes in characteristics other than those selected for, and behavior is no exception to this rule. Moreover, the existence of such inbred strains constitutes perhaps the most important single advantage of animals as subjects, since it enables simplifying assumptions regarding the homozygosity or genetic uniformity of such strains to be made in analysis of the outcome of crosses. Members of inbred strains are theoretically as alike as monozygotic twin pairs, so that genetic relationships—which in human populations can be investigated only after widespread efforts to find them—can be multiplied at will in laboratory animals.
This approach allows a more sensitive analysis of the determinants, both environmental and genetic, of the behavioral phenotype under observation. In addition, the nature of the genetic forces can be further differentiated into considerations of the average dominance effects of the genes in volved, the extent to which they tend to increase or decrease the metrical expression of the behavioral phenotype, and the extent to which the different strains involved possess such increasers or de creases. Finally, rough estimates of the number of these genes can be given. But the analysis depends upon meeting requirements regarding the scaling of the metric upon which the behavior is measured and is essentially a statistical one. That is, only average effects of cumulative action of the relatively large number of genes postulated as in volved can be detected. Gone are the elegantly simple statistics derived from the classical Men-delian analyses of genes of major effect, often displaying dominance, like those encountered incertain human inborn errors of metabolism. There is little evidence of the existence of comparable genes of major effect mediating behavior in laboratory animals, although some have been studied in in sects, especially the fruit fly.
A typical investigation of a behavioral phenotype might take the form of identifying two inbred strains known to differ in a behavioral trait, measuring individuals from these strains, and then systematically crossing them and measuring all offspring. When this was done for the runway performance of mice, an attribute related to their temperamental wildness, the results, analyzed by the techniques of biometrical genetics, showed that the behavior was controlled by at least three groups of genes (a probable underestimate). The contributions of these groups were additive to each other and independent of the environment when measured on a logarithmic scale but interacted with each other and with the environment on a linear scale. These genes showed a significant average dominance effect, and there was a preponderance of dominant genes in the direction of greater wildness. The heritability ratio of the contributions of “nature” and “nurture” was around seven to three.
The use of inbred lines may be restricted to first filial crosses if a number of such crosses are made from several different lines. This increases precision of analysis in addition to allowing a proportionate decrease in the amount of laboratory work. One investigation examined the exploratory behavior of six different strains of rats in an open field of the kind used for the selection mentioned above. On a linear scale there were no untoward environmental effects, including specifically prenatal maternal ones. The heritability ratio was high, around nine to one; and while there was a significant average dominance component among the genes determining exploration, there was no preponderance of dominants or recessively acting genes among increasers or decreasers. The relative standing in this respect of the parental strains could be established with some precision.
Limitations. While the methods described above have allowed the emergence of results that ultimately may assist our understanding of the mechanisms of behavioral inheritance, it cannot be said that much substantial progress has yet been made. Until experiments explore the effect of a range of different genotypes interacting with a range of environments of psychological interest and consequence, little more can be expected. Manipulating heredity in a single standard environment or manipulating the environment of a single standard genotype can only provide conclusions so limited to both the genotypes and conditions employed that they have little usefulness in a wider context. When better experiments are performed, as seems likely in the next few decades, then problems of some sociological importance and interest will arise in the application of these experiments to the tasks of maximizing genetic potential and perfecting environmental control for the purpose of so doing. A new eugenics may well develop, but grappling with the problems of its impact on contemporary society had best be left to future generations.
P. L. Broadhurst
[Directly related are the entriesEugenics; Evolution; Mental Disorders, article onGenetic Aspects. Other relevant material may be found inIndividual Differences, article onSex Differences; Instinct; Intelligence and Intelligence Testing; Mental Ertardation; Psychology, article onConstitutional Psychology.]
Broadhurst, P. L. 1960 Experiments in Psychogenetics: Applications of Biometrical Genetics to the Inheritance of Behavior. Pages 1-102 in Hans J. Eysenck (editor), Experiments in Personality. Volume 1: Psychogenetics and Psychopharmacology. London: Routledge.→ Selection and crossbreeding methods applied to laboratory rats.
Catteix, RaymondB.; Stice, GlenF.; and Kristy, Nor TonF. 1957 A First Approximation to Nature-Nurture Ratios for Eleven Primary Personality Factors in Objective Tests. Journal of Abnormal and Social Psychology 54:143–159. → Pioneer multivariate analysis combining twin study and familial correlations.
Fuller, JohnL.; and Thompson, W. Robert 1960 Be havior Genetics. New York: Wiley. → A comprehen sive review of the field.
Mather, Kenneth1949 Biometrical Genetics: The Study of Continuous Variation. New York: Dover. → The classic work on the analysis of quantitative char acteristics.
Shields, James1962 Monozygotic Twins Brought Up Apart and Brought Up Together: An Investigation Into the Genetic and Environmental Causes of Variation in Personality. Oxford Univ. Press.
The best available definition of population genetics is doubtless that of Malècot: “It is the totality of mathematical models that can be constructed to represent the evolution of the structure of a population classified according to the distribution of its Mendelian genes” (1955, p. 240). This definition, by a probabilist mathematician, gives a correct idea of the “constructed” and abstract side of this branch of genetics; it also makes intelligible the rapid development of population genetics since the advent of Mendelism.
In its formal aspect this branch of genetics might even seem to be a science that is almost played out. Indeed, it is not unthinkable that mathematicians have exhausted all the structural possibilities for building models, both within the context of general genetics and within that of the hypotheses—more or less complex and abstract—that enable us to characterize the state of a population.
Two major categories of models can be distinguished: determinist models are those “in which variations in population composition over time are rigorously determined by (a) a known initial state of the population; (b) a known number of forces or ‘pressures’ operating, in the course of generations, in an unambiguously defined fashion” (Male-cot 1955, p. 240). These pressures involve mutation, selection, and preferential marriages (by consanguinity, for instance). Determinist models, based on ratios that have been exactly ascertained from preceding phenomena, can be expressed only in terms of populations that are infinite in the mathematical sense. In fact, it is only in this type of population that statistical regularities can emerge (Malecot 1955). In these models the composition of each generation is perfectly defined by the composition of the preceding generation.
Stochastic models, in contrast to determinist ones, involve only finite populations, in which the gametes that, beginning with the first generation, are actually going to give birth to the new generation represent only a finite number among all possible gametes. The result is that among these active, or “useful,” gametes (Malecot 1959), male or female, the actual frequency of a gene will differ from the probability that each gamete had of carrying it at the outset.
The effect of chance will play a prime role, and the frequencies of the genes will be able to drift from one generation to the other. The effects of random drift and of genetic drift become, under these conditions, the focal points for research.
The body of research completed on these assumptions does indeed form a coherent whole, but these results, in spite of their brilliance, are marked by a very noticeable formalism. In reality, the models, although of great importance at the conceptual level, are often too far removed from the facts. In the study of man, particularly, the problems posed are often too complex for the solutions taken directly from the models to describe concrete reality.
Not all these models, however, are the result of purely abstract speculation; construction of some of them has been facilitated by experimental data. To illustrate this definition of population genetics and the problems that it raises, this article will limit itself to explaining one determinist model, both because it is one of the oldest and simplest to under stand and because it is one of those most often verified by observation.
A determinist model. Let us take the case of a particular human population: the inhabitants of an island cut off from outside contacts. It is obvious that great variability exists among the genes carried by the different inhabitants of this island. The genotypes differ materially from one another; in other words, there is a certain polymorphism in the population—polymorphism that we can define in genetic terms with the help of a simple example.
Let us take the case of autosome (“not connected with sex”) gene a, transmitting itself in a mono-hybrid diallely. In relation to it individuals can be classified in three categories: homozygotes whose two alleles are a (a/a); heterozygotes, carriers of a and its allele a’ (a/a’); and the homozygotes who are noncarriers of a (a’/a’). At any given moment or during any given generation, these three categories of individuals exist within the population in certain proportions relative to each other.
Now, according to Mendel’s second law (the law of segregation), the population born out of a cross between an individual who is homozygote for a (a/a) and an individual who is homozygote for a’ (a’/a’) will include individuals a/a, a/a’, and a’/a’ in the following proportions: one-fourth a/a, one-half a/a’, and one-fourth a’/a’. In this popu lation the alleles a and a’ have the same frequency, one-half, and each sex produces half a and half a’. If these individuals are mated randomly, a simple algebraic calculation quickly demonstrates that individuals of the generation following will be quan titatively distributed in the same fashion: one-fourth a/a, one-half a/a’, and one-fourth a’/a’. It will be the same for succeeding generations.
It can therefore be stated that the genetic structure of such a population does not vary from one generation to the other. If we designate by p the initial proportion of a/a individuals and by q that of a’/a’ individuals, we get p + q = 1, or the totality of the population. Applying this system of symbols to the preceding facts, it can be easily shown that the proportion of individuals of all three categories in the first generation born from a/a and a’/a’ equals p2, 2pq, q2. In the second and third generation the frequency of individuals will always be similar: p2, 2pq, q2.
Until this point, we have remained at the individual level. If we proceed to that of the gametes carrying a or a’ and to that of genes a and a’, we observe that their frequencies intermingle. In the type of population discussed above, the formula p2, 2pq, q2 still applies perfectly, therefore, to the gametes and genes. This model, which can be regarded as a formalization of the Hardy-Weinberg law, has other properties, but our study of it will stop here. (For a discussion of the study of isolated populations, see Sutter & Tabah 1951.)
Model construction and demographic reality. The Hardy-Weinberg law has been verified by numerous studies, involving both vegetable and animal species. The findings in the field of human blood groups have also been studied for a long time from a viewpoint derived implicitly from this law, especially in connection with their geographic distribution. Under the system of reproduction by sexes, a generation renews itself as a result of the encounter of the sexual cells (gametes) produced by individuals of both sexes belonging to the living generation. In the human species it can be said that this encounter takes place at random. One can imagine the advantage that formal population genetics can take of this circumstance, which can be compared to drawing marked balls by lot from two different urns. Model construction, already favored by these circumstances, is favored even further if the characteristics of the population utilized are artificially defined with the help of a certain number of hypotheses, of which the following is a summary description:
(1) Fertility is identical for all couples; there is no differential fertility.
(2) The population is closed; it cannot, there fore, be the locus of migrations (whether immigration or emigration).
(3) Marriages take place at random; there is no assortative mating.
(4) There are no systematic preferential marriages (for instance, because of consanguinity).
(5) Possible mutations are not taken into consideration.
(6) The size of the population is clearly denned. On the basis of these working hypotheses, the whole of which constitutes panmixia, it was possible, not long after the rediscovery of Mendel’s laws, to construct the first mathematical models. Thus, population genetics took its first steps forward, one of which was undoubtedly the Hardy-Weinberg law.
Mere inspection of the preceding hypotheses will enable the reader to judge how, taken one by one, they conflict with reality. In fact, no human population can be panmictic in the way the models are.
The following evidence can be cited in favor of this conclusion:
(1) Fertility is never the same with all couples. In fact, differential fertility is the rule in human populations. There is always a far from negligible sterility rate of about 18 per cent among the large populations of Western civilization. On the other hand, the part played by large families in keeping up the numbers of these populations is extremely important; we can therefore generalize by emphasizing that for one or another reason individ uals carrying a certain assortment of genes reproduce themselves more or less than the average number of couples. That is what makes for the fact that in each population there is always a certain degree of selection. Hypothesis (1) above, essential to the construction of models, is therefore very far removed from reality.
(2) Closed populations are extremely rare. Even among the most primitive peoples there is always a minimum of emigration or immigration. The only cases where one could hope to see this condition fulfilled at the present time would be those of island populations that have remained extremely primitive.
(3) With assortative mating we touch on a point that is still obscure; but even if these phe nomena remain poorly understood, it can nevertheless be said that they appear to be crucial in determining the genetic composition of populations. This choice can be positive: the carriers of a given characteristic marry among each other more often than chance would warrant. The fact was demonstrated in England by Pearson and Lee (1903): very tall individuals have a tendency to marry each other, and so do very short ones. Willoughby (1933) has reported on this question with respect to a great number of somatic characteristics other than height—for example, coloring of hair, eyes and skin, intelligence quotient, and so forth. Inversely, negative choice makes individuals with the same characteristics avoid marrying one another. This mechanism is much less well known than the above. The example of persons of violent nature (Dahlberg 1943) and of red-headed individuals has been cited many times, although it has not been possible to establish valid statistics to support it.
(4) The case of preferential marriages is not at all negligible. There are still numerous areas where marriages between relatives (consanguineous marriages) occur much more frequently than they would as the result of simple random encounters. In addition, recent studies on the structures of kinship have shown that numerous populations that do not do so today used to practice preferential marriage—most often in a matrilinear sense. These social phenomena have a wide repercussion on the genetic structure of populations and are capable of modifying them considerably from one generation to the other.
(5) Although we do not know exactly what the real rates of mutation are, it can be admitted that their frequency is not negligible. If one or several genes mutate at a given moment in one or several individuals, the nature of the gene or genes is in this way modified; its stability in the population undergoes a disturbance that can considerably transform the composition of that population.
(6) The size of the population and its limits have to be taken into account. We have seen that this is one of the essential characteristics important in differentiating two large categories of models.
Demography and population genetics
The above examination brings us into contact with the realities of population: fertility, fecundity, nuptiality, mortality, migration, and size are the elements that are the concern of demography and are studied not only by this science but also very often as part of administrative routine. Leaving aside the influence of size, which by definition is of prime importance in the technique of the models, there remain five factors to be examined from the demographic point of view. Mutation can be ruled out of consideration, because, although its importance is great, it is felt only after the passage of a certain number of generations. It can therefore be admitted that it is not of immediate interest.
We can also set aside choice of a mate, because the importance of this factor in practice is still unknown. Accordingly, there remain three factors of prime importance: fertility, migration, and preferential marriage. Over the last decade the progressive disappearance of consanguineous marriage has been noted everywhere but in Asia. In many civilized countries marriage between cousins has practically disappeared. It can be stated, therefore, that this factor has in recent years become considerably less important.
Migrations remain very important on the genetic level, but, unfortunately, precise demographic data about them are rare, and most of the data are of doubtful validity. For instance, it is hard to judge how their influence on a population of Western culture could be estimated.
The only remaining factor, fertility (which to geneticists seems essential), has fortunately been studied in satisfactory fashion by demographers. To show the importance of differential fertility in human populations, let us recall a well-known cal culation made by Karl Pearson in connection with Denmark. In 1830, 50 per cent of the children in that country were born of 25 per cent of the parents. If that fertility had been maintained at the same rate, 73 per cent of the second-generation Danes and 97 per cent of the third generation would have been descended from the first 25 per cent. Similarly, before World War I, Charles B. Davenport calculated, on the basis of differential fertility, that 1,000 Harvard graduates would have only 50 descendants after two centuries, while 1,000 Rumanian emigrants living in Boston would have become 100,000.
Measurement of fertility
Human reproduction involves both fecundity (capacity for reproduction) and fertility (actual reproductive performance). These can be estimated for males, females, and married couples treated as a reproductive unit. Let us rapidly review the measurements that demography provides for geneticists in this domain.
Crude birth rate. The number of living births in a calendar year per thousand of the average population in the same year is known as the crude birth rate. The rate does not seem a very useful one for geneticists: there are too many different groups of childbearing age; marriage rates are too variable from one population to another; birth control is not uniformly diffused, and so forth.
General fertility rate. The ratio of the number of live births in one year to the average number of women capable of bearing children (usually defined as those women aged 15 to 49) is known as the general fertility rate. Its genetic usefulness is no greater than that of the preceding figure. Moreover, experience shows that this figure is not very different from the crude birth rate.
Age-specific fertility rates. Fertility rates according to the age reached by the mother during the year under consideration are known as age-specific fertility rates. Demographic experience shows that great differences are observed here, depending on whether or not the populations are Malthusian—in other words, whether they practice birth control or not. In the case of a population where the fertility is natural, knowledge of the mother’s age is sufficient. In cases where the population is Malthusian, the figure becomes interesting when it is calculated both by age and by age group of the mothers at time of marriage, thus combining the mother’s age at the birth of her child and her age at marriage. This is generally known as the age-specific marital fertility rate. If we are dealing with a Malthusian population, it is preferable, in choosing the sample to be studied, to take into consideration the age at marriage rather than the age at the child’s birth. Thus, while the age at birth is sufficient for natural populations, these techniques cannot be applied indiscriminately to all populations.
Family histories. Fertility rates can also be calculated on the basis of family histories, which can be reconstructed from such sources as parish registries (Fleury & Henry 1965) or, in some countries, from systematic family registrations (for instance, the Japanese koseki or honseki). The method for computing the fertility rate for, say, the 25-29-year-old age group from this kind of data is first to determine the number of legitimate births in the group. It is then necessary to make a rigorous count of the number of years lived in wedlock between their 25th and 30th birthdays by all the women in the group; this quantity is known as the group’s total “woman-years.” The number of births is then divided by the number of “woman-years” to obtain the group’s fertility rate. This method is very useful in the study of historical problems in genetics, since it is often the only one that can be applied to the available data.
Measurement of reproduction
Let us leavefer tility rates in order to examine rates of reproduction. Here we return to more purely genetic considerations, since we are looking for the mechanism whereby one generation is replaced by the one that follows it. Starting with a series of fertility rates by age groups, a gross reproduction rate can be calculated that gives the average number of female progeny that would be born to an age cohort of women, all of whom live through their entire reproductive period and continue to give birth at the rates prevalent when they themselves were born. The gross reproduction rate obtaining for a population at any one time can be derived by combining the rates for the different age cohorts.
A gross reproduction rate for a real generation can also be determined by calculating the average number of live female children ever born to women of fifty or over. As explained above, this rate is higher for non-Malthusian than for Malthusian populations and can be refined by taking into consideration the length of marriage.
We have seen that in order to be correct, it is necessary for the description of fertility in Malthusian populations to be closely related to the date of marriage. Actually, when a family reaches the size that the parents prefer, fertility tends to approach zero. The preferred size is evidently related to length of marriage in such a manner that fertility is more closely linked with length of marriage than with age at marriage. In recent years great progress has been made in the demographic analysis of fertility, based on this kind of data. This should en ablegeneticists to be more circumspect in their choice of sections of the population to be studied.
Americans talk of cohort analysis, the French of analysis by promotion (a term meaning “year” or “class,” as we might speak of the “class of 1955”). A cohort, or promotion, includes all women born within a 12-month period; to estimate fertility or mortality, it is supposed that these women are all born at the same moment on the first of January of that year. Thus, women born between January 1, 1900, and January 1, 1901, are considered to be exactly 15 years old on January 1, 1915; exactly 47 years old on January 1, 1947; and so forth.
The research done along these lines has issued in the construction of tables that are extremely useful in estimating fertility in a human population. As we have seen, it is more useful to draw up cohorts based on age at marriage than on age at birth. A fertility table set up in this way gives for each cohort the cumulative birth rate, by order of birth and single age of mother, for every woman surviving at each age, from 15 to 49. The progress that population genetics could make in knowing real genie frequencies can be imagined, if it could concentrate its research on any particular cohort and its descendants.
Demography of genie frequencies
This rapid examination of the facts that demography can now provide in connection with fertility clearly reveals the variables that population genetics can use to make its models coincide with reality. The models retain their validity for genetics because they are still derived from basic genetic concepts; their application to actual problems, however, should be based on the kind of data mentioned above. We have voluntarily limited ourselves to the problem of fertility, since it is the most important factor in genetics research.
The close relationship between demography and population genetics that now appears can be illustrated by the field of research into blood groups. Although researchers concede that blood groups are independent of both age and sex, they do not explore the full consequences of this, since their measures are applied to samples of the population that are ‘representative” only in a demographic sense. We must deplore the fact that this method has spread to the other branches of genetics, since it is open to criticism not only from the demographic but from the genetic point of view. By proceeding in this way, a most important factor is overlooked—that of genie frequencies.
Let us admit that the choice of a blood group to be studied is of little impor tance when the characteristic is widely distributed throughout the population—for instance, if each individual is the carrier of a gene taken into account in the system being studied (e.g., a system made up of groups A, B, and O). But this is no longer the case if the gene is carried only by a few individuals—in other words, if its frequency attains 0.1 per cent or less. In this case (and cases like this are common in human genetics) the structure of the sample examined begins to take on prime importance.
A brief example must serve to illustrate this cardinal point. We have seen that in the case of rare recessive genes the importance of consan guineous marriages is considerable. The scarcer that carriers of recessive genes become in the pop ulation as a whole, the greater the proportion of such carriers produced by consanguineous marriages. Thus if as many as 25 per cent of all individuals in a population are carriers of recessive genes, and if one per cent of all marriages in that population are marriages between first cousins, then this one per cent of consanguineous unions will produce 1.12 times as many carriers of recessive genes as will be produced by all the unions of persons not so related. But if recessive genes are carried by only one per cent of the total population, then the same proportion of marriages between first cousins will produce 2.13 times as many carriers as will be produced by all other marriages. This production ratio increases to 4.9 if the total frequency of carriers is .01 per cent, to 20.2 if it is .005 per cent, and to 226 if it is .0001 per cent. Under these conditions, one can see the importance of the sampling method used to estimate the frequency within a population, not only of the individuals who are carriers but of the gametes and genes themselves.
Genealogical method. It should be emphasized that genetic studies based on genealogies remain the least controversial. Studying a population where the degrees of relationship connecting individuals are known presents an obvious interest. Knowing one or several characteristics of certain parents, we can follow what becomes of these in the descendants. Their evolution can also be considered from the point of view of such properties of genes as dominance, recessiveness, expressivity, and penetrance. But above all, we can follow the evolution of these characteristics in the population over time and thus observe the effects of differential fertility. Until now the genealogical method was applicable only to a numerically sparse population, but progress in electronic methods of data processing permits us to anticipate its application to much larger populations (Sutter & Tabah 1956).
Dynamic studies. In very large modern populations it would appear that internal analysis of cohorts and their descendants will bring in the future a large measure of certainty to research in population genetics. In any case, it is a sure way to a dynamic genetics based on demographic reality. For instance, it has been recommended that blood groups should be studied according to age groups; but if we proceed to do so without regard for demographic factors, we cannot make our observations dynamic. Thus, a study that limits itself to, let us say, the fifty- to sixty-year-old age group will have to deal with a universe that includes certain genetically “dead” elements, such as unmarried and sterile persons, which have no meaning from the dynamic point of view. But if a study is made of this same fifty- to sixty-year-old age group and then of the twenty- to thirty-year-old age group, and if in the older group only those individuals are considered who have descendants in the younger group, the dynamic potential of the data is maximized. It is quite possible to subject demographic cohorts to this sort of interpretation, because in many countries demographic statistics supply series of individuals classified according to the mothers’ age at their birth.
Other demographic factors
This discussion would not be complete if we did not stress another aspect of the genetic importance of certain demographic factors, revealed by modern techniques, which have truly created a demographic biology. Particularly worthy of note are the mother’s age, order of birth, spacing between births, and size of family.
The mother’s age is a great influence on fecundity. A certain number of couples become in capable of having a second child after the birth of the first child; a third child after the second; a fourth after the third; and so forth. This sterility increases with the length of a marriage and especially after the age of 35. It is very important to realize this when, for instance, natural selection and its effects are being studied.
The mother’s age also strongly influences the frequency of twin births (monozygotic or dizygotic), spontaneous abortions, stillborn or abnormal births, and so on. Many examples can also be given of the influence of the order of birth, the interval between births, and the size of the family to illustrate their effect on such things as fertility, mortality, morbidity, and malformations.
It has been demonstrated above how seriously demographic factors must be taken into consideration when we wish to study the influence of the genetic structure of populations. We will leave aside the possible environmental influences, such as social class and marital status, since they have previously been codified by Osborn (1956/1957) and Larsson (1956–1957), among others. At the practical level, however, the continuing efforts to utilize vital statistics for genetic purposes should be pointed out. In this connection, the research of H. B. Newcombe and his colleagues (1965), who are attempting to organize Canadian national statistics for use in genetics, cannot be too highly praised. The United Nations itself posed the problem on the world level at a seminar organized in Geneva in 1960. The question of the relation between demography and genetics is therefore being posed in an acute form.
These problems also impinge in an important way on more general philosophical issues, as has been demonstrated by Haldane (1932), Fisher (1930), and Wright (1951). It must be recognized, however, that their form of Neo-Darwinism, although it is based on Mendelian genetics, too often neglects demographic considerations. In the future these seminal developments should be renewed in full confrontation with demographic reality.
[Directly related are the entriesCohort Analysis; Fertility; Fertility Control. Other relevant ma terial may be found inNuptiality; Race; SocialBehavior, Animal, article onThe Regulation of Animal Populations.]
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Since 1900, the study of genetics has made two major contributions to the theoretical understanding of the biology of race. First is the replacement of earlier theories of racial heredity based on the blending of characteristics by the newer, genetical notion of a breeding population incorporating gene frequencies based on the particulate, or Mendelian, theory of heredity. Because of the use of a misleading theory of heredity, nearly all of the writing on subspecific taxonomy of the human species before 1900, and unfortunately much written since then, is incorrect.
The second contribution of genetics has been to place race in the perspective of a general theory of organic evolution. This interpretation of racial biology derives from those parts of population genetics initially developed by Wright (1931; 1951) and Haldane (1932) and interpreted variously by Dobzhansky (1962), Mayr (1963), Simpson (1961), and Morton and Yasuda (1963). We can not adequately understand the evolutionary history of mankind either in terms of individuals or in terms of the species as a whole because individuals do not evolve and the details of the evolutionary process are not necessarily uniform for all subdivisions of the species. This is why it is of theoretical importance to recognize subspecies in evolutionary biology, whether or not they are given taxonomic recognition.
Race and subspecies. A “race” is a category logically more inclusive than the notion of “individual” and less inclusive than the notion of “species.” Most contemporary authorities equate the anthropological concept of race with the zoological concept of subspecies.
Subspecies and races are two or more genetically distinguishable populations of a species that have separate distributions but which can, and do, inter breed freely in overlap zones or when brought into contact. The frequency of gene exchange between races is highest in the contact zone and decreases away from it.
Since the geographical change in gene frequency is gradual, any attempt to separate sharply local populations into races having different gene frequencies is arbitrary. Often groups defined by one set of genetically determined characteristics show a clear geographical distribution. The distribution of a group defined by another set of alleles may be mapped with equal certainty; usually the geographical boundaries of two such classifications will not coincide very closely.
Knowledge of race. Statements about race involve two distinct kinds of knowledge, one about attributes, the other about relationships. Usually our knowledge of the phenotypes used to define races is direct and observational; in principle there may be full agreement among experts regarding the attributes which characterize a given group of people. Our knowledge about the biological relationships among individuals often is indirect, being based on interviews or inferred from geographical, societal, or cultural circumstances. Two individuals are biological relatives when one developed from a zygote formed by a gamete from the other or both developed from zygotes formed by gametes from a common ancestor. Each individual is connected by gametes to his parents, to the members of one or more races, and, ultimately, to the species. In practice it is rare to know directly all relevant parent-child links connecting the members of a race. Genetics makes rules for predicting the distribution of phenotypes-genotypes among individuals of known relationship. In the study of race such rules are used to infer relationships of populations of individuals whose phenotypes-genotypes are known.
Particulate versus blending heredity. The molecular, paniculate nature of the genetic material and the facts of gene segregation and recombination have great theoretical significance for the biology of race.
If the hereditary materials were blended (as nineteenth-century biologists assumed) like solutes in solvents, every member of a breeding population would soon reach hereditary uniformity and, barring mutation and hybridization, a “pure” race would be established in each locality. The genetic material would become unique to each local breeding population, and genotypes of offspring would necessarily be a midway blend of those of their parents. But, in fact, segregation and recombination do produce novel genie variation within the local breeding population. Genes in body cells occur in pairs (AA, Aa, aa). When gametes are formed, the members of each pair segregate so that each gamete has only one gene from each pair (A or a) and each child receives only one member of a pair from each parent (i.e., two parents of genotype Aa may produce a child who is AA, Aa, or aa). Also, each pair of genes at other loci (non-alleles) is capable of undergoing segregation separately, so that two pairs of genes which are together in one parent (say AAbb or aaBB) may be recombined in the child (AaBb), the recombination rate being slower for linked than for independent nonalleles.
Before the effective start of genetics in 1900, it was believed that hereditary material was a homo geneous substance which could be mixed or diluted but was identical in all members of a “pure” race. If two individuals were alike in one hereditary as pect, they would be alike in all others. Within a “pure” race all variation was due to environmental effects. Genetics now shows that hereditary materialrial is a heterogeneous collection of separate par ticles which need not be the same even in close relatives. Two closely related individuals may have many genes in common but may differ in others. Likewise, because of parallel mutation, unrelated people may have some genes of the same function even though these genes are not derived from a common ancestor.
Before genetics, it was believed that the hereditary material differed in kind between races of the same species, just as two elements differ. The pre-genetic view of race involved what Aristotle called the “essence” of material bodies. Just as atoms of copper and tin are of different construction, so two races were thought to have hereditary material different in essence; the difference was, accordingly, not in degree but in kind. As atoms of copper can join those of tin to make bronze, so it was thought “pure” races come together to form a mixed race. It was possible to think of individuals of mixed races as being “mostly Alpine” or “mostly Nordic,” in the same way that it was possible to think of alloys with varying fractions of different metals. Using an analogy from ceramics, certain anthropologists even as late as the 1940s spoke of race X having a “wash” of race Y. As is shown below, such beliefs are refuted by the identification of homologous genes in different races.
Kinds of gene differences between races. It is clear we should not speak of racial characteristics, only of racial differences. Differences between any two races express differently occurring frequencies of autosomal genes. These may be written as follows:
(pA + qa)2(p’B + q’b)2 … (p”N + q“n)2 = 1,
(rA’ + sa’)2(r’B’ + s’b’) … (r”N’ + s“n’)2 = 1.
Here A,a, N’,n’ represent sets of alleles with frequencies p + q=l, r + s=l, where O^p, r. (The arrays of possible genotypes can be derived as the products of the squares of the above binomials. If there are k alleles at a locus, the binomial is replaced by a fe-nomial. For sex-chromosomal loci, the array of genotypes in the heterogametic sex is given by the first power of the fe-nomial.) By identifying and comparing the frequencies of genes between populations, we may distinguish four kinds of differences:
(1) If the same kinds and frequencies are present in both, the two populations are identical.
(2)If gene frequencies equal zero or unity in one population but are not fixed (0 p, r 1) in the other, or if some but not all frequencies are unity in one and zero in the other, the two populations are qualitatively different in gene frequency at one or more but not at all loci; they show a specific difference in kind.
(3) If the allele at all loci is zero in one population and unity in the other, there is a general dif ference in kind.
(4) If none of the frequencies equal zero or unity, the populations differ in degree not in kind.
Prior to the twentieth century, most anthropolo gists and biologists assumed the differences between local populations within the same race were of sort (1) and those between races were of sort (3). The early students assumed the genetic material of (pure) races was homogeneous within, and qualitatively different between, races.
Today we have frequency information on nearly fifty genes in which some of the alleles at each locus are common enough in one or more human populations to be of anthropological interest. several hundred rare major genes are known to medical genetics. The knowledge gained from both human and general genetics demonstrates that “pure” races in the sense of homogeneous breeding populations differing in the kind of genes present at all loci do not exist in the human species or in any known sexual species of animals or plants.
For at least eight known human chromosomal loci, specific differences in kind of sort (2) are known to hold between some pairs of human races. For instance, the gene associated with blood group A of the ABO series is present in all known European populations, as is the gene for B, but gene A is absent in some, and gene B is absent in many American Indian populations. The genes for the Diego, Henshaw, Hunter, Kell, Lutheran, Rhesus, and hemoglobin ACS loci show detectable differences in kind between two or more human races.
Differences of sort (4), i.e., cases where the same kinds of genes are present in different frequency, constitute the most common kind of genetic divergence observed between local and geographical races of man for both normal and nearly all of the identified deleterious major genes. (See Dobzhansky 1962 or recent textbooks of human genetics for further data on the major genes mentioned above.)
Typology and race. The pregenetic typological approach to racial anthropology used at least three different concepts of “types.” All are unacceptable to modern genetics, each for a different reason.
(a) The average type of a population is defined by a set of traits used to identify members of the (”pure“) race. Thus Nordics in Sweden and else where are characterized by tall stature, long heads, blond hair, and blue eyes. From the genetic point of view there are two basic difficulties in this approach: Only a small fraction of the members of any local breeding population exhibit the full set of traits used to define the type, and the vast amount of genetic variability known to be present in all sexually reproduced populations is not recognized. Retzius and Fiirst found only 10.07 per cent of a large sample of Swedish conscripts had all four of the above diagnostic traits for Nordics (Dahlberg 1942). Since a breeding population has no average genotype, it cannot have an average phenotype; thus, it is misleading to pick out a typical (average) member of any race.
(b) Morphological types, which occur in groups of two to about ten in a given population, are also defined by a cluster of traits. The racial history of a population is explained by the supposed coming together and intermixture of individuals belonging to the several types, all wrongly assumed to be stable over time and to represent ancestral stocks (see, e.g., Hooton 1926; 1931).
An example of misinterpreted history comes from western Europe, where most people in the north are tall, blond, and blue-eyed; most in the south are short, brunet, and brown-eyed; and those in the midland are assorted in stature and pigmentation, with short blonds, tall brunets, brown-eyed blonds, etc. Those who use morphological types to explain racial history assume the people of the midland are a mixture of migrants from the north and south. But this is not necessarily what happened in history; the “mixed” group may be the actual common ancestor of the two “pure” groups concentrated by natural selection in the two extremes of the geographical range. The rather scanty information with historical depth suggests this latter explanation is the correct one for the origin of the “morphological races” of western Europe.
The processes of gene segregation and recombination, together with those of parallel and recurrent mutation, negate the possibility of sorting the members of an interbreeding population into morphological types representing ancestral stocks. A simple hypothetical example will illustrate this. The initial generation includes two “races” (Table 1). Genes A and a axe autosomal and lack dominance. Since the A allele is fixed in one and the a allele in the other, each “race” is genotypically invariant for the traits. Now if north and south send migrants to
midland and there hybridize, the F1 hybrids will all have genotype Aa and phenotype XY. Intercrossing of the F1,s will produce all three genotypes in subsequent generations of the new midland “race.” But in this mixed “race,” individuals of type XY are more closely related (a distance of one parent-child step) to their homozygous parents of type X or Y than are individuals of type X or Y who turn up in subsequent generations (distant by two or more parent-child steps). It may also happen that, through mutation rather than descent, members of the population may come to possess genes identical to those of the founding generation.
Sameness of phenotype represents neither degree of closeness nor the fact of relationship in a mixed population. Further, sameness of some specific phenotype does not guarantee that a given individual in a mixed population will inherit other desirable or undesirable traits from an ancestor of the same specific phenotype. (See Dahlberg 1943 for extension of this argument to other kinds of major genes and to polygenes.)
(c) The individual types of the Czekanowski group of Polish anthropologists are “racial ele ments” defined by a cluster of traits assumed to be controlled by one, or several closely inked, pleiotropic gene(s). These genes simultaneously affect the set of type-defining traits in whatever population they are found. This typology is compatible with population genetics if the frequencies of the “racial elements” have-the empirical properties of the frequencies of pleiotropic genes, a possibility, however, not supported by family studies or by the fit of observed population frequencies of “racial elements” to those expected for genotypes in equi librium Mendelian populations (Bielicki, 1965).
Modes of change in gene frequency. The theory of population genetics builds upon a population model in which gene frequencies are in equilibrium. The relative frequencies of genes and of genotypes remain steady in a randomly mated breeding population if mutation does not prefer entially add or subtract genes, if genes flowing into the population from the outside differ neither in kind nor in frequency from those native to the local population, if there is no differential fertility or mortality between genes and genotypes, and if the breeding population is large enough in numbers that genetic drift does not occur. If these equilibrium conditions do not hold, gene and/or genotype frequencies will change until a new steady state is attained.
Inbreeding and assortative mating, the two most important departures from random mating, do not by themselves change gene frequencies but only the relative frequencies of genotypes; such changes are usually in the direction of increased homozygosity.
Mutation. Mutation is the primary source of all gene variation. The molecular basis of mutation is change in the sequence of nucleotides in DNA. Estimated spontaneous mutation rates in man vary from about one to one hundred mutations per million gametes. The rates are specific for loci and alleles but may vary somewhat according to the mutagenic nature of the environment. Probably the mutation rates for the more common human genes are sufficiently small compared with the rates for other modes of change that mutation is not a major determinant of observable local and regional differences in gene frequencies. However, it should be emphasized that mutation is repetitive; within a species, a mutation is not likely to occur only once, nor to occur in one major race and not in another.
Gene flow. Gene flow refers to introduction of genes from outside the local breeding population. The process is general for loci, haploid sets of genes being introduced on each occasion. In terms of the change in frequency, the most important type of gene flow involves recurrent, more or less regular introduction of gametes from neighboring groups which are partially isolated reproductively. When the parental populations are sufficiently dissimilar in gene frequencies, gene flow is called race mixture. Mixture may result in very rapid changes in gene frequencies. When clines are reflections of gene flow, the gene frequencies of several loci should show similar cline distribution when the incoming and native populations differ in those frequencies.
Recurrent gene flow has been an important factor preventing the splitting of mankind into allopatric species. Before the development of extrasomatic modes of transportation, the vast majority of gene flow involved neighboring populations. With the development of more rapid transportation, the rate and distance of gene flow increased. Since a.d. 1600 mixture has been the most significant factor in population differentiation.
Selection. Selection is the main guiding force in race formation. Genes or genotypes which, on the average, increase genetic fitness will become more frequent in later generations. Genetic fitness is defined solely in terms of differential fertility and/or mortality. For a given environment, genes may be harmful, neutral, or beneficial. The population frequencies of harmful genes are determined by the balance between their rate of entry by mutation and their rate of removal by selection. Neutral genes must be very rare, their spread very slow, and their replacement by more successfully adaptive genes very rapid. An important class of genes are those with increased fitness in heterozygotes; such genes spread rapidly through local populations and, given gene flow, through those sections of the species population with similar environmental conditions. These genes with a selective advantage of the heterozygote may have stable equilibrium frequencies largely determined by selection coefficients and nearly independent of initial gene frequencies and mutation rates. If polygenes are additive, selection acts on each locus independently of the others. Linkage between polygenes, unless very strong, is unimportant for selection rates.
Genetic drift. The two genes at each autosomal locus in an individual are a sample, one from each parent, of the four genes at that locus in the parents. With small population numbers, random fluctuation in this sampling process may change gene frequencies, leading to concentration or fixation of some alleles and loss of others in local populations. The resulting irregular and patchy gene-frequency distributions may be nonadaptive.
The origin of races. The formation of races is not characteristic of all sexual species. Race formation requires partial reproductive isolation. Change in gene frequency is the fundamental event in the formation of races. Race formation, i.e., adaptation to local conditions, must occur in all successful, widespread species with partially isolated local populations. Given the raw materials of gene diversity, the genetic subdivision of a species depends largely on local selection pressures, on the one hand, and gene flow, on the other. If there is much gene flow, local races cannot form; if there is less gene flow, clines may develop; if there is little gene flow, local races will differentiate. If any of the local populations are small in number, say under one hundred, there may be considerable loss and fixation of genes by random genetic drift.
Race differences in behavior. Human races differ in languages and culture as well as in genes. One of the most significant contributions of the social sciences to the general knowledge of the twentieth century is the demonstration that a large fraction of functionally important differences between human groups in learned behavior is largely independent of race, or as we put it, independent of genie differences distinguishing races.
Differences in the frequency of major genes between local populations as well as major geographical races are well established for some behavioral traits, e.g., the ability to taste phenylthiocarbamide and the four kinds of X-linked partial color blindness, although these behavioral variations are of limited functional significance in human societies.
One sort of theoretical model in population genetics suggests we should observe statistical differences in the frequencies of polygenes making up the genetical components of intellectual abilities and temperament (e.g., Hogben 1932, p. 169; Sturtevant 1954). Equally valid theoretical models support tne opposite conclusion by suggesting that the genotypes making up the capacity underlying cultural learning are a species characteristic maintained in equilibrium in all human populations (e.g., Dobzhansky 1962, p. 320). Since the genetic basis of intelligence is polygenic and since we can not identify polygenes in man, precise information about racial, i.e., inherited, differences in general intelligence is simply not available. But it seems clear that if differences between major races exist in general intellectual abilities, these differences are small in magnitude compared with the range of genetic variation within all major races (Spuhler &Lindzey 1967).
J. N. Spuhler
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Genetics is the branch of biology concerned with the science of heredity, or the transfer of specific characteristics from one generation to the next. Genetics, from the Greek genno (give birth), focuses primarily on genes, coded units found along the DNA (deoxyribonucleic) acid molecules of the chromosomes, housed by the cell nucleus. Together, genes make up
the blueprints that determine the entire development of the species of organisms down to specific traits, such as the color of eyes and hair.
DNA is a molecule of nucleic acid that contains the genetic code of a living thing, or the physical characteristics that are passed down to a child from parents. Its shape is similar to a ladder that has been twisted into the shape of a winding staircase—what scientists call a twisted double strand double helix. All living things that contain cells have DNA. In mammals, such as humans, the pieces of DNA are grouped into structures called chromosomes, which are located in cell nuclei. The genetic material that is needed for humans to develop and grow is contained in DNA. The hereditary characteristics that pass from one generation to the next are also contained in DNA. An example of a hereditary characteristic that is inherited from parent to child is the blonde hair of a son born to parents who both have blonde hair.
Geneticists are concerned with three primary areas of gene study: how genes are expressed and regulated in the cell, how genes are copied and passed on to successive generations, and what are the genetic basis for differences between the species. Although the science of genetics dates back at least to the nineteenth century, little was known about the exact biological makeup of genes until the 1940s. Since that time, genetics has moved to the forefront of biological research.
DNA was first sequenced in 1977 by the independent work of English biochemist Frederick Sanger (1918–) and American molecular biologists Walter Gilbert (1932–) and Allan M. Maxam. The first genome completely sequenced occurred in 1980 when bacteriophage φ-X174 (a particular virus that had infected a bacterium) was sequenced. In 1989, American physician-geneticist Francis S. Collins (1950–) and Chinese geneticist Lap-Chee Tsui (1950–) sequenced the first human gene.
In 1990, the Human Genome Project (HGP) began in the United States. It was a coordinated international scientific project to understand and map the human genome so that all of its genes were identified. Other countries participating in HGP included France, Germany, Japan, and the United Kingdom. HGP members identified about 20,000 to 25,000 genes in the nucleus of a human cell and mapped the location of these genes on the 23 pairs of human chromosomes.
The Human Genome Project and Celera Genomics simultaneously released an initial draft of the human genome in February 2001. The HGP completed the final sequencing of the human genome (with 99% of the genome sequenced to a 99.99% accuracy) in April 2003. The result will not only be a greater understanding of the human body, but provide new insights into the origins of disease and the formulation of possible treatments and cures.
The study of heredity the science called genetics— started in the 1800s, when scientists first began trying to explain the existence of different species and variations within the same species. At that time, French biologist Jean Baptiste de Lamarck (1744–1829) strongly believed that acquired characteristics would improve when routinely used over time. Those characteristics that were not used simply faded away. Lamarck also maintained that acquired characteristics were inherited from one generation to the next. In other words, Lamarck believed that if a giraffe continuously stretched its neck to reach for food, it would develop a longer neck. Further, the longer neck would be passed on to the next giraffe generation. Although his belief that acquired characteristics were inherited was incorrect, Lamarck was on the right track. He implied that traits can be inherited from generation to generation—that species undergo long-term evolutionary changes.
In 1859, English naturalist Charles Darwin (1809-1882) published his landmark book The Origin of Species, in which he outlined his theory of evolution through natural selection. Darwin believed that members of a particular species have slightly different characteristics. In the competition for space, food, and shelter, some of these characteristics would make a particular plant or animal better able to survive and produce offspring than others of its species. Therefore, these advantageous characteristics would persist in future generations, while those less advantageous ones would disappear as their carriers died out. After centuries or millennia of competition or natural selection, recent members of a species might be quite different from their ancestors. This theory gained advocates like English physician Thomas Huxley (1825–1895), who, did more than anyone else to overcome opposition to Darwinian theory. But even with all the support, Darwin’s theory still lacked an explanation for how the differences in species occurred.
Although humans have known about inheritance for thousands of years, the first scientific evidence for the existence of genes came in 1866. At that time, Austrian monk and geneticist Gregor Johann Mendel (1822–1937) published the results of a study of hybridization of plants—the combining of two individual species with different genetic make-ups to produce a new individual. Working with pea plants with specific characteristics such as height (tall and short) and color (green and yellow), Mendel bred one type of plant for several successive generations. He found that certain characteristics appeared in the next generation in a regular pattern. From these observations, he deduced that the plants inherited a specific biological unit (which he called factors (now called alleles), genes determining different forms of a single characteristic) from each parent. Mendel also noted that when factors or alleles pair up, one is dominant (which means it determines the trait, like tallness) while the other is recessive (which means it has no bearing on the trait). It is now understood that alleles may be single genes or sets of genes working together, each contributing to the final form of a physical characteristic (multiple allelism).
In 1884, German biologist August Weissmann proposed that a special hereditary substance existed in the egg nucleus, which he termed germ plasm. His theories concerning the behavior of this substance— later identified as chromosomes—were eventually proved correct. However, he mistakenly believed that the germ plasm passed intact from generation to generation, unchanged by any environmental factors. Weissmann’s theory, therefore, could not adequately account for the changes that occurred between generations and drove Darwin’s theory of evolution.
The period of classical genetics, in which researchers had no knowledge of the chemical constituents in cells that determine heredity, lasted well into the twentieth century. However, several advances made during that time contributed to the growth of genetics. In the eighteenth century, scientists used the relatively new technology of the microscope to discover the existence of cells, the basic structures in all living organisms. By the middle of the nineteenth century, they had discovered that cells reproduce by dividing.
Although Mendel laid the foundation of genetics, his work began to take on true significance in 1903 when German biologist Theodor Henrich Boveri (1862–1915) and American geneticist Walter Stanborough Sutton (1877–1916) independently proposed a chromosomal theory of inheritance. They discovered that chromosomes during gamete production behave like the socalled Mendel’s particles behave. In 1910, American zoologist and geneticist Thomas Hunt Morgan (1866-1946) confirmed the existence of chromosomes through experiments with fruit flies. He also discovered a unique pair of chromosomes called the sex chromosomes, which determined the sex of offspring. Morgan deduced that specific genes reside on chromosomes from his observation that an X-shaped chromosome was always present in flies that had white eyes. A later discovery showed that chromosomes could mutate or change structurally, resulting in a change in characteristics which could be passed on to the next generation.
More than three decades passed before scientists began to delve into the specific molecular and chemical structures that make up chromosomes. In the 1940s, a research team led by Oswald Avery (1877–1955) discovered that deoxyribonucleic acid (DNA) was responsible for transformation of non-pathogenic bacteria into pathogenic ones. The final proof that DNA was the specific molecule that carries genetic information was made by Alfred Day Hershey (1908–1997) and Martha Cowles Chase (1927–2003) in 1952. They used radioactive label to differentiate between viral protein and DNA, proving that over 80% of viral DNA entered bacterial cell causing infection, while protein did not cause infection.
The most important discovery in genetics occurred in 1953, when American microbiologist James Watson (1928–) and English scientist Francis Crick (1916–2004) solved the mystery of the exact structure of DNA. The two scientists used chemical analyses and x-ray diffraction studies performed by other scientists to uncover the specific structure and chemical arrangement of DNA. X-ray diffraction is a procedure in which parallel x-ray beams are diffracted by atoms in patterns that reveal the atom’s atomic weight and spatial arrangement. A month after their double-helix model of DNA appeared in scientific journals, the two scientists showed how DNA replicated. Armed with these new discoveries, geneticists embarked on the modern era of genetics, including efforts like genetic engineering, gene therapy, and a massive project to determine the exact location and function of all of the 20,000 to 25,000 genes that make up the human genome.
Genetic information is contained in the chromosomes, threadlike structures composed of DNA, and present in the nuclei of all cell types and are passed to daughter cells during cell division. Multicellular organisms contain two types of cells—body cells (or somatic cells) and germ cells (or reproductive cells). Germ cells are the ones that pass on the genetic information to the progeny. In contrast to somatic cells that contain dual copies of chromosomes in each cell, germ cells replicate through a process called meiosis, which ensures that the germ cells have only a single set of chromosomes, a condition called haploidy (designated as n). The somatic cells of humans have 23 pairs of chromosomes (46 chromosomes overall), a condition known as diploid (or 2n). Through the process of meiosis, a new cell, called a haploid gamete, is created with only 23 chromosomes: this is either the sperm cell of the father or the egg cell of the mother. The fusion of egg and sperm restores the diploid chromosome number in the zygote. This cell carries all the genetic information needed to grow into an embryo and eventually a full-grown human with the specific traits and attributes passed on by the parents. Offspring of the same parents differ because the sperm cells and egg cells vary in their gene sequences, due to random recombination.
The somatic, or body cells are the primary components of functioning organisms. The genetic information in these cells is passed on through a process of cell division called mitosis. Unlike meiosis, mitosis is designed to transfer the identical number of chromosomes during cell regeneration or renewal. This is how cells grow and are replaced in exact replicas to form specific tissues and organs, such as muscles and nerves. Without mitosis, an organism’s cells would not regenerate, resulting not only in cell death, but possible death of the entire organism. (It is important to note that some organisms reproduce asexually by mitosis alone.)
To understand genes and their biological function in heredity, it is necessary to understand the chemical makeup and structure of DNA. Although some viruses carry their genetic information in the form of ribonucleic acid (RNA), most higher life forms carry genetic information in the form of DNA, the molecule that makes up chromosomes.
The complete DNA molecule is often referred to as the blueprint for life because it carries all the instructions, in the formation of genes, for the growth and functioning of most organisms. This fundamental molecule is similar in appearance to a spiral staircase, which is also called a double helix. The sides of the DNA double helix ladder are made up of alternate sugar and phosphate molecules, like links in a chain. The rungs, or steps, of DNA are made from a combination of four nitrogen-containing bases—two purines (adenine [A] and guanine [G]) and two pyria set of 64midines (cytosine [C] and thymine [T]). The four letters designating these bases (A, G, C, and T) are the alphabet of the genetic code. Each rung of the DNA molecule is contains a combination of two of these letters, one jutting out from each side. In this genetic code, A always combines with T, and C with G to make what is called a base pair. Specific sequences of these base pairs, which are bonded together by atoms of hydrogen, make up the genes.
While a four-letter alphabet may seem rather small for constructing the comprehensive vocabulary that describes and determines the myriad life forms on the Earth, the sequences or order of these base pairs are nearly limitless. For example, various sequences or rungs that make up a simple six base gene could be ATCGGC, TAATCG, AGCGTA, or ATTACG, and so on. Each one of these combinations has a different meaning. Different sequences provide the code not only for the type of organism, but also for specific traits like brown hair and blue eyes. The more complex an organism, from bacteria to humans, the more rungs or genetic sequences appear on the ladder. The entire genetic makeup of a human, for example, contains about three billion base pairs, with the average gene unit being a few thousand base pairs long. Except for identical twins, no two humans have exactly the same genetic information. About 98% of DNA in chromosomes carry no genetic information.
Genetic information is duplicated during the process of DNA replication, which begins a few hours before the initiation of cell division (mitosis). To produce identical genetic information during mitosis, the hydrogen bonds holding together the two halves of the DNA ladder unzip, in presence of proteins called helicases, to expose single strands of DNA. These old strands act as templates to make new DNA molecules. Replication is initiated by this separation of DNA, and requires short DNA fragments (primers) to start synthesis of a new DNA strand by specific cellular enzymes called DNA polymerases. DNA rarely mutates during replication, as the proofreading and repair enzymes make sure that any errors are quickly repaired to protect the accuracy of the genetic information. Once completed, each new half of the DNA ladder has the identical information as the old one. The fact that T always combines with A and C with G achieves this process, therefore if the template had a sequence ATGCTG the newly made second strand will be TACGAC. When cell mitosis is completed, each new cell contains an exact replica of the DNA.
Cells contain hundreds of different proteins and its functions are dependent on which of the thousands of types of different proteins it contains. Proteins are made up of chains of amino acids. The arrangement of the amino acids to build specific proteins is determined by the base pair sequence contained or encoded in DNA. This genetic information has to be converted to proteins building over half of all solid body tissues and control most biological processes within and among these tissues. This is achieved by using the genetic code, which is a set of 64 (or, 43) triplets of bases (called codons) corresponding to each amino acid and the initiation and termination signals for protein synthesis.
As the sites of protein production lie outside the cell nucleus, the instructions for making them have to be transported out of the nucleus. The messenger that carries these instructions is messenger RNA, or mRNA (a single stranded molecule that has a mirror image of the base pairs on the DNA). The mRNA is made in the nucleus during a process called transcription and a single molecule of RNA carries instructions for making only one protein. After being exported out of the nucleus it is transported to ribosomes, which are the protein factories in the cell. In ribosomes the information from mRNA is decoded to produce a protein. This process is called translation. The flow of information is only one way from DNA to RNA and to protein. Therefore, characteristics acquired during an organism’s life, such as larger muscles or the ability to play the piano, cannot be inherited. However, people may have genes that make it easier for them to acquire these traits through exercise or practice.
The expression of the products of genes is not equal, and some genes will override others in expressing themselves as an inherited characteristic. The offspring of organisms that reproduce sexually contain a set of chromosome pairs, half from the father, and half from the mother. However, normally people do not have one blue eye and one brown eye, or half brown hair and half blond hair because most genetic traits are the result of the expression of either the dominant or the recessive genes. If a dominant and a recessive gene appear together (the heterozygous condition), the dominant will always win, producing the trait for which it is coded. The only time a recessive trait (such as the one for blond hair) expresses itself is when two recessive genes are present (the homozygous condition). As a result, parents with heterozygous genes for brown hair could produce a child with blond hair if the child inherits two recessive blondhair genes from the parents. The genes residing in the chromosome’s DNA can also be present in alternative forms called alleles. It is important to note that some characteristics are a result of presence of various alleles, e.g. pink snapdragon flowers or blood types.
This hereditary law also holds true for genetic diseases. Neither parent may show signs of a genetic disease, caused by a defective gene, but they can pass the double-recessive combination on to their children. Some genetic diseases are dominant and others are recessive. Dominant genetic defects are more common because it only takes one parent to pass on a defective allele. A recessive genetic defect requires both parents to pass on the recessive allele that causes the disease. A few inherited diseases (such as Down syndrome) are caused by abnormalities in the number of chromosomes, where the offspring has 47 chromosomes instead of the normal 46.
The DNA molecule is extremely stable, ensuring that offspring have the same traits and attributes that will enable them to survive as well as their parents. However, a certain amount of genetic variation is necessary if species are to adapt by natural selection to a changing environment. Often, this change in genetic material occurs when chromosome segments from the parents physically exchange segments with each other during the process of meiosis. This is known as cross over or intrinsic recombination.
Genes can also change by mutations on the DNA molecule, which occur when a mutagen alters the chemical or physical makeup of DNA. Mutagens include ultraviolet light and certain chemicals. Genetic mutations in somatic (body) cells result in malfunctioning cells or a mutant organism. These mutations result from a change in the base pairs on the DNA, which can alter cell functions and even give rise to different traits. Somatic cell mutations can result in disfigurement, disease, and other biological problems within an organism. These mutations occur solely within the affected individual.
When mutations occur in the DNA of germ (reproductive) cells, these altered genes can be passed on to the next generation. A germ cell mutation can be harmful or result in an improvement, such as a change in body coloring that acts as camouflage. If the trait improves an individual organism’s chances for survival within a particular environment, it is more likely to become a permanent trait of the species because the offspring with this gene would have a greater chance to survive and pass on the trait to succeeding generations.
Mutations are generally classified into two groups, spontaneous mutations and induced mutations. Spontaneous mutations occur naturally from errors in coding during DNA replication. Induced mutations come from outside influences called environmental factors. For example, certain forms of radiation can damage DNA and cause mutations. A common example of this type of mutating agent is the ultraviolet rays of the Sun, which can cause skin cancer in some people who are exposed to intense sunlight over long periods of time. Other mutations can occur due to exposure to artificially made chemicals. These types of mutations modify or change the chemical structure of base pairs.
Population genetics is the branch of genetics that focuses on the occurrence and interactions of genes in specific populations of organisms. One of its primary concerns is evolution, or how genes change from one generation to the next. By using mathematical calculations that involve an interbreeding population’s gene pool (the total genetic information present in the individuals within the species), population geneticists delve into why similar species vary among different populations that may, for example, be separated by physical boundaries such as bodies of water or mountains.
As outlined in the previous section, genetic mutations may cause changes in a population if the mutation occurs in the germ cells. Many scientists consider mutation to be the primary cause of genetic change in successive generations. However, population geneticists also study three other factors involved in genetic change or evolution: migration, genetic drift, and natural selection.
Migration occurs when individuals within a species move from one population to another, carrying their genetic makeup with them. Genetic drift is a natural mechanism for genetic change in which specific genetic traits coded in alleles (alternate states of functioning for the same gene) may change by chance often in a situation where organisms are isolated, as on an island.
Natural selection, a theory first proposed by Charles Darwin in 1858, is a process that occurs over successive generations. The theory states that genetic changes that enhance survival for a species will come to the forefront over successive generations because the gene carriers are better fit to survive and are more likely reproduce, thus establishing a new gene pool, and eventually, perhaps, an entirely new species. One proposed mechanism of natural selection is gradualism, which predicts very slow and steady accumulation of beneficial genes. Punctuated equilibrium, in contrast, depicts natural selection as occurring in brief, but accelerated periods of survival of the fittest with lengthy periods of relative stagnation of genetic change in populations. Some scientists hold that both processes occur and have occurred.
More than any other biological discipline, genetics is responsible for the most dramatic breakthroughs in biology and medicine today. Scientists are rapidly advancing in their ability to engineer genetic material to achieve specific characteristics in plants and animals. The primary way to genetically engineer DNA is called gene cloning, in which a segment of one DNA molecule is removed and then inserted, into another DNA molecule. This process takes advantage of restriction enzymes to cut DNA into fragments of different lengths and ligase to re-create new molecules. Restriction enzymes act as molecular scissors, cutting larger molecules (like DNA) at specific sites. The ends of these fragments are sticky in that they have an affinity for complimentary ends of other DNA fragments. DNA ligase acts as a glue to join the ends of the two molecules together. This approach has applications in agriculture and medicine.
In agriculture, genetic engineering is used to produce transgenic animals or plants, in which genes are transferred from one organism to another. This approach has been used to reduce the amount of fat in cattle raised for meat, or to increase proteins in the milk of dairy cattle that favor cheese making. Fruits and vegetables have also been genetically engineered so they do not bruise as easily, or so they have a longer shelf life at the grocery store. On the other hand, in medicine, genetic engineering provided great advancements in production of antibiotics, hormones, and vaccines, understanding disease mechanisms and in therapy. Gene therapy is currently being developed and used as it provides the opportunity to introduce specific genes into the body to correct a genetic defect or to enhance the body’s capabilities to fight off disease and repair itself. Because many inherited or genetic diseases are caused by the lack of an enzyme or protein, scientists hope to one day treat the unborn by inserting genes to provide the missing enzyme.
Genetic fingerprinting (DNA typing) is based on each individual’s unique genetic code. To identify parentage, diagnose inherited diseases in prenatal laboratories or the presence of someone at a crime, scientists use molecular biology techniques such as DNA fingerprinting by applying restriction fragment length polymorphisms (RFLPs) analysis (identifying the characteristic patterns in DNA cut with the restriction enzymes), microsattelite analysis (looking at the small specific DNA sequences), DNA hybridization, DNA sequencing or polymerase chain reaction (PCR). Development of PCR provides the ability to analyze small amounts of DNA acquired from hair, semen, blood, fingernail fragments, or fetal cells by utilizing DNA polymerase enzyme (the same enzyme used naturally by cells in mitosis) to create identical copies of a DNA molecules from small samples.
One of the most exciting recent developments in genetics is the completion of the Human Genome Project (HGP). This project provided a complete genetic road map outlining the location and function of the 20,000 to 25,000 genes found in human cells encoded in about three billion bases. The first human genome draft sequences were published in February 2001 by the Celera company and the HGP consortium in the journals Science and Nature, respectively. Due to technological advances and huge international cooperation throughout the project, the essentially complete genome was finished on April 14, 2003, a full five years ahead of schedule, with 99% of the genome sequenced at 99.9% accuracy. Then, in May 2006, the last chromosome sequence was published in the journal Nature As a result, genetic researchers will have easy access to specific genes to study how the human body works and to develop therapies for diseases. Gene maps for other species of animals are also being developed.
Full sequencing of many bacterial genomes, yeast, Caenorhabditis elegans, Drosophila, mouse, and human genomes has brought about a new era in genetics, and a development of a new area—genomics, or the study of the sequences of genes within living things. Sequencing means that the structure of deox-yribonucleic acid (DNA) from a particular living thing is discovered—what scientists called mapped. Specifically, genomic scientists identify and analyze the structure of genes within segments of DNA. Inside any organism, the complete set of chromosomes—or all the genetic information contained in genes—is called its genome. The set of chromosomes inside people is called the human genome. Availability of full DNA sequences of multiple organisms allows the comparative analysis (comparative genetics) of genomes allowing gene identification, finding of regulatory sequences and tracing evolution.
Genetic analysis proved very successful in Mendelian diseases. New challenges for genetics are the studies of common complex diseases such as asthma, obesity and hypertension. These diseases are caused by interaction of multiple genes and the
Allele— Any of two or more alternative forms of a gene that occupy the same location on a chromosome.
Base — A chemical unit that makes up part of the DNA molecule. There are four bases: adenine (A) and guanine (G), which are purines, and cytosine (C) and thymine (T), which are pyrimidines.
Chromosomes— The structures that carry genetic information in the form of DNA. Chromosomes are located within every cell and are responsible for directing the development and functioning of all the cells in the body.
DNA— Deoxyribonucleic acid; the genetic material in a cell. Chromosomes are made of DNA.
Dominant (dominant gene)— An allele of a gene that results in a visible phenotype if expressed in a heterozygote.
Gene— A discrete unit of inheritance, represented by a portion of DNA located on a chromosome. The gene is a code for the production of a specific kind of protein or RNA molecule, and therefore for a specific inherited characteristic.
Genetic recombination— New configurations produced when two DNA molecules are broken and rejoined together during meiosis.
Heredity— Characteristics passed on from parents to offspring.
Heterozygous— Two different forms of the same allele pair on the chromosome.
Homozygous— Two identical forms of the same allele pair on the chromosome.
Meiosis— The process of cell division in germ or reproductive cells, producing haploid genetic material.
Mitosis— The process of cell division in somatic, or body, cells, producing no change in genetic material.
Proteins— Macromolecules made up of long sequences of amino acids. They make up the dry weight of most cells and are involved in structures, hormones, and enzymes in muscle contraction, immunological response, and many other essential life functions.
Recessive— Refers to the state or genetic trait that only can express itself when two genes, one from both parents, are present and coded for the trait, but will not express itself when paired with a dominant gene. (See Dominant; Allele)
Ribonucleic acid— RNA; the molecule translated from DNA in the nucleus that directs protein synthesis in the cytoplasm; it is also the genetic material of many viruses.
Transcription— The process of synthesizing RNA from DNA
environment, making their analysis even more difficult. Geneticists analyze DNA sequence to correlate any changes with the disease (association studies). Small fragments of repetitive DNA sequence (microsattelites) or single nucleotide polymorphisms (SNPs) are analyzed. Such studies require analysis of large control (healthy) population in addition to the affected group before any conclusions can be made. Solving of the puzzle of complex traits is going to be possible by combining molecular genetics, biostatis-tics, further clinical and computational/bioinformati-cal analysis.
Despite the promise of genetics research, many ethical and philosophical questions arise. Many of the concerns about this area of research focus on the increasing ability to manipulate genes. There is a fear that the results will not always be beneficial. For example, some fear that a genetically re-engineered virus could turn out to be extremely virulent, or deadly, and may spread if there is no way to stop it.
Another area of concern is the genetic engineering of human traits and qualities. Altering genetic material, for example, will let doctors diagnose and treat many diseases and help scientists improve the safety of foods. It will also give scientists the ability to change the physical and psychological traits of people. If a woman has an inherited heart problem, doctors could alter her genetic material so babies born to her in the future will not have this problem. The goal is to produce people with specific traits such as better health, improved looks, or even high intelligence. While these traits may seem to be desirable on the surface, the concern arises about who will decide exactly what traits are to be engineered into human offspring, and whether everyone will have equal access to an expensive technology. Scientists could also alter such minor physical characteristics as hair color and height. Many people do not think it is ethical to change such traits by altering genetic materials. Some fear that the result could be domination by a particular socio-economic group.
Genetic information involves the gathering and storing of materials related to a person’s DNA. Issues have been raised as to what type of rules should be set up for the gathering and storing of such DNA information. Questions are being asked such as: How should that information be used? Who should be told? Who should be in charge of storing the information? Questions about personal privacy and other ethical considerations concerning genetic information have yet to be determined. Lawmakers, health insurance companies, medical organizations, and United States citizens will all take a part in answering these sensitive questions. As the scientific capabilities increase within genetic engineering, more genetic information will become available. Humans will—no doubt—face more difficult ethical and privacy questions about genomics in the future.
Despite these fears and concerns, genetic research continues. In an effort to ensure that the science is not abused in ways harmful to society, governments in the United States and abroad have created panels and organizations to oversee genetic research. For the most part, international committees composed of scientists and ethical experts state that the benefits of genetic research for medicine and agriculture far outweigh the possible abuses.
Carlson, Elof Axel. Mendel’s Legacy: The Origin of Classical Genetics. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press, 2004.
Hartl, Danial, and Elizabeth Jones. Genetics: Analysis of Genes and Genomes. Sudbury, MA: Jones and Bartlett Publishers, 2005.
Lewin, Benjamin. Essential Genes. Upper Saddle River, NJ: Pearson Education, 2006.
Lewis, Ricki. Human Genetics: Concepts and Applications. Boston, MA: McGraw-Hill, 2005.
Brookes, Anthony. “Rethinking Genetic Strategies to Study Complex Diseases.” Trends in Molecular Medicine (November 2001):512–6.
Guo, Sun-Wei, and Kenneth Lange, “Genetic Mapping of Complex Traits: Promises, Problems, and Prospects.” Theoretical Population Biology (February 2000):1–11.
Philips, Tamara J., and John K. Belknap, “Complex-trait Genetics: Emergence of Multivariate Strategies.” Nature Reviews. Neuroscience (June 2002):478–485
Genetics is the field of scientific research that studies gene activity in plants, animals, and humans. Genes are segments of DNA (deoxyribonucleic acid) found in each living cell; each of these DNA segments codes for a protein, thereby yielding a phenotypic effect. All life on Earth shares the chemical make-up of DNA, even though each species differs in the number and function of genes. Scientists estimate that human DNA contains between thirty-one and thirty-six thousand genes arrayed over two pairs of twenty-three chromosomes. The forty-six human chromosomes are strands of DNA, with each of the twenty-three strand pairs arranged as a double helix. The DNA strands are composed of four base chemicals: adenine (A ), guanine (G ), cytosine (C ), and thymine (T ). These four bases are typically identified by their single letter abbreviations (A,G,C,T ) and constitute an alphabet, so to speak, that carries genetic information from DNA to tissue formation and bodily activity.
Modern genetics began in the nineteenth century with the research of an obscure Austrian monk, Gregor Mendel (1822–1884), who discovered patterns of inheritance in pea plants. Mendelian laws of inheritance still stand as the foundation for contemporary genetics. The twentieth century added the chemical work of molecular biology, including the post World War II discovery of the double helix structure of DNA by James Watson (b. 1928) and Francis Crick (b. 1916). At the turn of the twenty-first century, the Human Genome Project had sequenced the three billion base pairs and nearly identified all the genes in the human genome. The complete genomes of a handful of plants and animals had also been identified.
In addition to molecular biology, which directly studies the chemical processes of genes, two other branches of genetics have become significant for religious reflection: behavioral genetics and sociobiology. Behavioral genetics employs statistical studies of phenotypical characteristics and social preferences to discern heritability probabilities. Central to such studies are monozygotic and heterozygotic twins raised apart. The assumption in such studies is that twins raised apart are excellent subjects because they provide opportunity to distinguish between genetic and environmental influences.
Sociobiology appeared in 1975 with publications by Harvard entomologist Edward O. Wilson (b. 1929). Wilson, having studied how ant societies are socially held together by chemical signals, purported by analogy that human breeding patterns, gender dominance, and caste systems are similarly explainable. Zoologist Richard Dawkins (b. 1941) shortly thereafter coined the term "selfish gene," which reinforced the central thesis of sociobiology. In Darwinian fashion the human organism does not live for itself; rather, its function in nature is to reproduce the genes for which it is the temporary carrier. In short, genetic forces drive evolution, including human evolution, and human social history, including religious history, can be explained by reference to genetic drives.
Theological issues raised by genetics
The apparent growth in knowledge regarding human nature cultivated by genetic research leads some religious thinkers to review their inherited anthropologies. Most theologians see the field of genetics as a challenge requiring response; a few see new genetic knowledge as a complement to long standing religious insight. Distinctively theological issues are few and are frequently embedded within the more plentiful and visible issues of ethics and public policy. Theological issues will be taken up immediately; ethical issues surrounding cloning and stem cell research will follow.
The first theological concern is genetic reductionism. Reductionism poses a theological threat everywhere in modern science. The form it takes in genetics is the vague cultural belief that "it's all in the genes." In the laboratory, methodological reductionism is necessary to foster research into gene function, but a threat comes with ontological reductionism and surmises that all of what constitutes human nature is reducible to the genes. During the early years of the Human Genome Project, DNA was described by some scientists as the "code of codes" or the "blueprint of humanity." Such biological reductionism seems to leave no room for independent influence on the part of spirit or culture, the dimensions wherein most religious traditions work.
A second and related concern is genetic determinism. If "it's all in the genes" and the DNA is the blueprint of who human beings are, then genes move into the position of determiners of human nature and human value. In the historical struggle between nature and nurture in the minds of intellectuals trying to explain human complexity, the new breed of genetic determinists stake their claim on nature. Relatively few molecular biologists advocate strong genetic determinism, whereas behavioral geneticists and sociobiologists reinforce it. Molecular biologists and philosophers who oppose an exclusive genetic determinism frequently appeal to two part determinism: genes plus environment. Some theologians locate human freedom in three part determinism: genes, environment, and the human self or person. In the latter case, the human self is emergent; the self is not reducible to either biological or environmental influences. Divine action in the human reality here is said to be holistic—that is, present to all three dimensions of biology, environment, and person.
A third and related concern is neo-Darwinian evolution. Nineteenth century Darwinism employed natural selection as the mechanism for explaining evolutionary change over time. Twentieth century neo-Darwinists such as Fransisco Ayala or Stephen Jay Gould add genetic mutation to the theory, adding detail to the manner in which natural selection works. Sociobiology extrapolates on neo-Darwinism by attempting to explain all of human culture including religious belief in terms of biological determinism. Sociobiologists (sometimes called evolutionary psychologists) contend that human culture is on a leash, a short leash, held by a genetic agenda. That agenda is the self-replication of genes using the human species as its vehicle. Human culture is structured so as to encourage reproduction and, hence, the perpetuation of genes. Human religion and human morality, whether theologians know it or not, is reducible to the agenda of selfish genes.
Those theologians who are attempting to incorporate sociobiology into their religious vision feel they must justify human transcendence of biology and the emergence of soul or spirit. Philip Hefner's theological anthropology, for example, argues that through evolutionary processes the genes have determined that we humans would be free. Some Christology's contend that Jesus marks a significant advance in evolutionary history, because with the Nazarene a precedent-setting life is led that transcends the selfish genetic agenda, and the possibility is opened for self-sacrificial loving. In contrast, some Muslim scholars find they must simply reject neo-Darwinian evolutionary theory because it makes no room for human spirit and because it fails to cohere with the anthropology of the Qur'an.
In summary, the theological community is accepting of the methodological reductionism within molecular biology that functions to yield advance in scientific research. However, theologians resist philosophical extrapolations that tend toward ontological reductionism or genetic determinism. Reductionism and determinism are insufficient, say theologians, to explain spiritual reality or ethical transcendence. Theologians defend human freedom and moral transcendence whether it complements the science or requires abandoning the science.
Genetic engineering consists of selecting, inserting, or removing individual genes in order to manipulate the genome of an organism. In agriculture and animal husbandry selective breeding to obtain preferred strains has been practiced for millennia. Modern genetic engineering adds chemical and mechanical methods for more sophisticated results.
In agriculture the genomes of plants are altered by genetic engineering to confer resistance to blight or resistance to herbicides in order to eliminate weeds while preserving the crops. Tomato genomes, for example, can be modified so as to stall final ripening during transport to market and then ripen just prior to going on sale. Such techniques dramatically increase the percentage of produce that becomes marketable. In Europe and other parts of the world popular movements against genetically modified foods (GMFs) have arisen. Fearing unknown possible health effects, opponents of GMFs lobby for accurate labeling so that the market can freely choose whether to consume them or not.
The engineering of farm animal genomes has two purposes. One is to obtain preferred strains of livestock, especially beef cattle. The other is to produce foods or pharmaceuticals for human consumption. An example of the latter case is the insertion of a human gene into a sheep genome to produce in the animal's milk a certain protein usable for treatment of a human disease. This use of animals for human betterment is itself controversial, with opponents arguing that turning animals into a means for human ends violates animal dignity.
To date, the genetic engineering of human genomes in the reproduction process has been limited to gene selection; it has not included gene insertion or removal. When in vitro multiple fertilized ova are examined, only those with the preferred genome may be implanted in the mother's uterus. This process is typically employed to eliminate known deleterious genes such as that for cystic fibrosis. In somatic therapy on living persons, however, more than selection is being tried. Genes that produce healthy blood have been inserted into bone marrow cells. Attempts are being made to send "knock out" genes into cancer tumors to turn off tumor growth by turning off telomerase activity.
An implicit theological issue that arises more often in the wider cultural debate than within specific religious communities is naturalism. Naturalism is the belief that nature apart from intervention by human technology is the source of value. Genetic engineering is a form of technology that alters the natural world people have inherited from evolutionary history. The promethean question arises implicitly: Is the natural world the source of human value, or, on the basis of humanly superimposed purposes, do people have the right to manipulate nature to meet these purposes? Much of the energy driving opposition to GMFs derives from naturalism. A similar naturalism is implicit in theological arguments, which presume that God's will is manifest in the genetic lottery resulting from sexual intercourse rather than through deliberate selection in vitro of the genetic code of future children.
The promethean question also arises with genetic futurism. As the present generation manipulates plant, animal, and human genomes, will this place humans in the position of guiding our evolutionary future? Does the human race possess the wisdom to choose a wholesome future or, like Prometheus of ancient Greek tragedy, will humans overstep their finite bounds and create an irreparable tragedy? Conservative theologians along with naturalist advocacy groups wish to put the brakes on genetic engineering and let nature take its course; whereas other religious leaders foresee immense benefits for health and wellbeing to be gained through genetic technology and contend that the human race must steward scientific advance.
The two most virulent ethical controversies over genetic research have been cloning and stem cells. The two are linked. The first successful experiment in reproductive animal cloning was accomplished at the Roslin Institute in Edinburgh, Scotland, where embryologist Ian Wilmut cloned the world famous sheep, Dolly. The details were published in the February 27, 1997, issue of Nature. Wilmut's Roslin team removed cells from the udder of a pregnant Finn Dorset ewe, placed them in a culture, and starved them of serum nutrients for a week until the cells became quiescent—that is, they arrested the normal cycle of cell division, inviting a state akin to hibernation. Second, they took an unfertilized egg, or oocyte, from a Scottish Blackface ewe and removed the nucleus. When removing the nucleus with the DNA, they left the remaining cytoplasm intact. Third, the scientists placed the quiescent cell next to the oocyte; then they introduced pulses of electric current. The gentle electric shock caused the cells to fuse, and the oocyte cytoplasm accepted the quiescent DNA. A second electric pulse initiated normal cell division. Fourth, after six days of cell division, the merged embryo was implanted into the uterus of another Blackface ewe and brought through pregnancy to birth on July 5, 1996. The newborn babe was named Dolly. The procedure was called somatic cell nuclear transfer (NT).
An important scientific question was answered with this experiment: Is cell differentiation reversible? The answer seems to be yes. Embryonic cells are predifferentiated. Adult cells are normally differentiated in order to perform the particular tasks of particular parts of the body. For example, genes for hair are turned on in the hair while genes for toenails are turned off in hair but on where the toenails belong. In theory, cloning could be accomplished by employing embryonic cells in their predifferentiated state. The accomplishment here was to make an adult differentiated cell function as an undifferentiated embryonic cell.
The procedure was not clean and easy. The successful cloning of Dolly was accompanied by numerous misfires. Out of 277 tries, the Roslin scientists were able to make only twenty-nine embryos survive beyond six days. At fourteen days 62 percent of the fetuses in ewe wombs were lost, a significantly greater proportion than the estimate of 6 percent after natural mating. Eight ewes gave birth to five lambs, with all but one dying shortly thereafter. Dolly was the only one to survive. Triumph is accompanied by loss. Noting this, many scientists including Wilmut himself have opposed the prospect of human cloning because of the safety argument—that is, until the process is perfected, too many human embryos would be destroyed as misfires.
Ethical issues raised by cloning
Ethical issues arising from cloning technology can be divided into two areas, human reproductive cloning and human therapeutic cloning. Therapeutic cloning will be taken up later in the discussion of stem cells. The public discussion over reproductive cloning seems to focus on human reproduction, not animals. Cloned cattle and sheep do not elicit the religious opposition connected to human births.
The overriding ethical issue is this: Should human beings be cloned? Back in 1971 James Watson predicted this debate. Watson, along with Francis Crick, won the 1962 Nobel Prize for medicine or physiology for the discovery of the double helix structure of DNA. Writing on cloning for the May 1971 issue of the Atlantic, Watson predicted that the first reaction of most people to the arrival of these asexually produced children would be one of despair. He then went on to suggest that people with strong religious backgrounds would want to de-emphasize all those forms of research that would circumvent the normal sexual reproductive process. The Watson prophecy seems to have found its fulfillment.
In a February 22, 1997, press release, Donald Bruce, Director of the Society, Religion and Technology Project of the Church of Scotland, said that cloning human beings would be ethically unacceptable as a matter of principle. According to Christian belief, he said, cloning would be a violation of the uniqueness of human life, which God has given to each of us and to no one else. The argument that each individual person has a unique identity that would be violated by cloning has been repeated in religious and secular circles with a high degree of frequency.
The structure of this argument applies three assumptions to the issue of cloning. The first assumption is that in order for a human person to have an individual identity he or she must have a unique genome. The second assumption is that God has ordained that each person have a genome that differs from every other person. The third assumption is that through this genetic technology human beings could accidentally produce two persons with the same identity and, thereby, violate the divine creator's intention. On the basis of these scientific and theological assumptions, the ethical conclusion drawn here is this: no cloning.
Those holding the alternative position reject these assumptions. Scientifically speaking, even though two individuals might end up with identical genotypes, they would not end up with identical phenotypes. DNA does not always express itself in lock step fashion. There are variations in expression and spontaneous mutations. In addition, environmental factors such as food and exercise and health care influence gene activity. If the DNA donor and clone are reared a generation apart in time let alone in separate locations, similarities will be noticeable, but differences will abound.
The existence of monozygotic twins is instructive. Like clones, identical twins are born with identical genomes. Despite what they share in common, they grow up as separate and distinct individuals. Each has his or her own interior consciousness, sense of self, thought processes, and ethical responsibility. Even if studies in behavioral genetics eventually show strong DNA influence on predispositions to certain forms of behavior, they remain two separate individuals with separate lives to lead. A clone would in effect be a delayed twin; due to the delay, a clone would probably experience even more independence than two born at the same time.
During the debate, the question arose: Would two clones share a single soul? No theological position to date has held that two twins share a single soul. Each has his or her own soul, his or her own connection to God. This by analogy would seem to apply to clones as well. The human soul, theologically speaking, is not formed from DNA as the phenotype is formed from the genotype. The soul is not a metaphysical appendage to the physical. In sum, the theological argument against cloning based on an alleged violation of a God-given identity appeared early in the debate but eventually dissipated under critical review.
The United States National Bioethics Advisory Commission (NBAC) studied cloning—a study that included interviews with leaders in Judaism, Islam, Hinduism, Buddhism, Evangelical Protestantism, Liberal Protestantism, and Roman Catholicism—and issued a report on June 6, 1997, with the following conclusion: At this time it is morally unacceptable for anyone in the public or private sector, whether in a research or clinical setting, to attempt to create a child using somatic cell nuclear transfer cloning. The principle argument against cloning was the safety argument, as enunciated above by Ian Wilmut. The report went on to ask the U.S. Congress to pass legislation setting a three to five year moratorium on the use of federal funding in support of human cloning, and it asked non-federally funded private sectors to comply voluntarily with this moratorium. The NBAC further recommended that religious groups carry on an ongoing discussion of the ethics of cloning. Even though legislation did not follow, religious groups have carried on the recommended discussion.
In addition to the safety and the identity arguments, a third has been raised against human reproductive cloning: the commodification argument. Cloning—as a form of designer baby making—might lead to the commodification or commercialization of children; this would constitute an assault on a child's dignity. Dignity in this case is not based upon genetic individuality but upon treatment as an end rather than a means. Designer babies serve the ends of the designers, the parents, not the ends of the child. Cloning along with other genetic technologies, critics fear, may play into the hands of economic forces that will tend to commodify newborn children. Commodification, not genetic uniqueness, would deny the sacred character of human individual life.
The cloning controversy deals primarily with human reproduction. The stem cell controversy moves into therapeutic cloning and related matters. The therapeutic promise is dramatic. Specifically, rejuvenation through transplantation of tissue grown in a laboratory from stem cells would be of enormous value for cardiomyocytes to renew heart muscle to prevent congestive heart failure; replacement of hematopoietic stem cells for producing healthy blood in bone marrow to resist infection by the HIV virus and to treat AIDS and possibly sickle cell anemia; cultivating endothelial cells to reline blood vessels as treatment for atherosclerosis, angina, and stroke due to arterial insufficiency; rejuvenating islet cells in the pancreas to produce natural insulin to fight diabetes; renewal of neurons in the brain to treat Parkinson's disease and victims of stroke; fibroblast and keratinocyte cells to heal skin in the treatment of burns; and chondrocytes or cartilage cells to treat osteoarthritis or rheumatoid arthritis. All this promise arises from human embryonic stem cells (hES cells), which are self-renewing—virtually immortal—and have the capacity to develop into any or all tissue types in the human body.
Two momentous laboratory discoveries are relevant. First is the isolation of human embryonic stem cells (hES cells) in August 1998 by James Thomson, an associate veterinarian in the University of Wisconsin's Regional Primate Research Center. Thomson began with fertilized ova—spare embryos from in vitro fertilization (IVF) not placed in a uterus—and cultured them to the blastocyst stage, about four to six days. At this point he removed the outer shell of the blastocyst, separated out the individual cells, and placed them on a feeder tray. The cells divided. They reproduced themselves. Because these cells are as yet undifferentiated—that is, they are pluripotent and able to make any part of a human body—they are the cells from which other cells stem. Because they replicate themselves indefinitely, Thomson in effect created an immortal line of embryonic stem cells.
Second, John Gearhart, a professor of gynecology and obstetrics at Johns Hopkins University School of Medicine, drew human embryonic germ cells (hEG cells) from fetal gonadal tissue in September 1998. These cells, when taken from an aborted fetus, resemble in nearly all respects the pluripotent stem cells described above.
It is not yet clear whether or not hES cells are identical to hEG. Both are pluripotent and equivalent in function. Yet, it may be discovered that different alleles appear in different hES, because hES cells could be imprinted by either the male or female source. The blastocyst stage of embryogenesis is a stage that avoids the gender imprint. What is not yet known is whether original gender imprint will matter. For the foreseeable future the two types of stem cells will be treated the same, yet controversy rages over Thomson's destruction of the blastocyst to obtain hES cells.
One goal of the research agenda is to learn just what turns genes on and off. Once scientists have gained the knowledge of triggering gene expression, they can apply it to pluripotent stem cells and direct the growth of selected bodily tissue. Particular organs could be grown in culture. Heart tissue or entire organs such as the pancreas or liver could be grown in the laboratory. These would be healthy rejuvenating organs ready for transplantation.
In order to transplant the laboratory grown organs, however, medical scientists need to override our immune system in order to avoid organ rejection. Two scenarios lie before us. One would be to create a universal donor cell that would be compatible with any organ recipient. The task here would be to disrupt or alter the genes within the cell responsible for the proteins on the cell's outer surface that label them as foreign to the recipient's immune system. This approach would be difficult. It would involve disrupting genes within the same DNA in which researchers are trying to express certain other genes. Exposing such cells to harsh conditions with rounds of different drugs may damage more than just the targeted surface proteins.
A preferable second scenario would be to make cells that are genetically compatible (histo-compatible) with the organ recipient—that is, to make cells with an identical genotype. If the organ genotype matches that of the recipient, no immune system rejection will take place.
This is the connection to cloning, or somatic cell nuclear transfer. One hypothetical scenario is to begin with an enucleated human oocyte, an egg with the DNA nucleus removed. Via somatic nuclear transplantation—cloning—one could insert the DNA nucleus of the future transplant recipient. By turning on selected genes, selected tissue could be grown ex vivo, outside the body, and then through surgery placed within the recipient. Because the implanted heart or liver tissue has the same genetic code as the recipient, no rejection would occur. This is in part the Dolly scenario, although it differs in that it grows only organ tissue and not an entire fetus.
Another variant or second scenario distinguishes itself sharply from Dolly, namely, one that eliminates the use of a fresh oocyte. Instead of an oocyte, the recipient's DNA nucleus would be placed in a non-egg cell, in the stem cell itself. The goal here would be to accomplish laboratory organ growth in a stem cell that is not an egg. To accomplish this, further research on cytoplasm's role in gene expression is required, as well as development of the nuclear transfer technology for insertion into the tiny stem cell.
Ethical issues raised by stem cells
On August 9, 2001, U.S. President George W. Bush announced that his government would support research on existing lines of stem cells, but would refrain from supporting the destruction of embryos to create new cell lines. The president thought he was settling an ethical dispute. Public policy, science, and ethics are inextricable.
Formulating the central ethical question raised by stem cell research is difficult because each of the two sides is oriented toward a different question. The embryo protection position begins with the question: How can we protect the dignity of the embryo? The beneficence or healing opportunity position begins with the question: How can scientific research lead to advances in human health and well-being? Each position is internally coherent, yet they are locked in controversy.
Those holding the embryo protection position lift their voices in defense of the apparently helpless embryo threatened with death at the hands of the laboratory executioner. The use of blastocysts and aborted fetuses leads opponents to criticize the scientific community for devaluing human life. They argue that the devaluation of humans at the very commencement of life encourages a policy of sacrificing the vulnerable, and this could ultimately put other humans at risk, such as those with disabilities and the aged, through a new eugenics of euthanasia. Pope John Paul II (1978–), in an elocution at Castel Gandolpho in August 2001, likened the destruction of blastocysts to obtain hES cells with infanticide. In effect, the embryo protection position sees the stem cell debate in terms of the abortion debate.
The major premise of this position is that each human embryo is the tiniest of human beings. The unspoken second premise is that, because an embryonic stem cell is a tiny human being, it has dignity. And, having dignity, the embryo providing the stem cell deserves protection from scientists who would use the name of medical research to destroy it. The nonmalificence or "do no harm" medical maxim applies here, and this maxim is violated in embryonic stem cell research.
In contrast, the healing opportunity position notes that the principle of beneficence goes beyond that of nonmalificence. Beyond avoiding harm, appeal to beneficence requires the active pursuit of human health and wellbeing. The central focus here is the good promised by stem cell research. Beneficence is a form of agape, selfless love. Decisive in the thinking of Christian supporters of medical research is Jesus' own ministry of healing, which set an example for his disciples. In many cities Christian groups have named their hospitals "Good Samaritan" after the key figure in one of Jesus' parables who administered healing to an abandoned victim of violence. From this perspective, secular medical research contributes to God's healing work on earth.
Embryo protectors accuse beneficence supporters of crass utilitarianism, of sacrificing innocent human beings in vitro for future hospital patients. Stem cell supporters repudiate the charge of utilitarianism, some even conceding the possibility of dignity applied to the early embryo. Relevant here is the observation that hES cells are derived from surplus embryos, from fertilized ova discarded in clinics. Such surplus embryos are slated for destruction in any case, either due to freezer burn or overt disposal. The beneficence position does not necessarily endorse the actual creation of new embryos for sacrifice to laboratory research; rather, it is satisfied with drawing some life-giving potential from an entity otherwise marked for disposal. Rather than deny dignity to the early embryo, beneficence advocates believe they can affirm embryo dignity yet still sustain justification for proceeding with health yielding research on stem cells.
The deliberate creation of fresh embryos for destruction in the laboratory would require an additional premise to attain ethical justification. The additional premise could be supplied by the developmentalists. Ethicists holding the developmentalist position frequently apply the fourteen-day rule. This is based on the observation that until an embryo attaches itself to the uterine wall and gastrulation occurs, a single individual fetus is not yet formed. Twining can still occur up until the appearance of the primitive streak that will become the backbone, thereby defining a single individual rather than multiple fetuses. By denying individuality to the embryo prior to the fourteenth day, some ethicists justify research at prior stages of development. Stem cells are harvested between the fourth and sixth days.
The Vatican has steadfastly rejected the fourteen-day rule. Donum Vitae in 1987 and subsequent papal elocutions have reiterated the classic doctrine of creationism and applied it to the socalled moment of conception. When the sperm fertilizes the egg during sexual intercourse, says Pope John Paul II, a third factor is present. God imparts a freshly created soul to the zygote. The presence of this eternal soul establishes personhood and dignity to the embryo. This makes it morally inviolable and, hence, protectable.
Genetics, culture, and religion
With the field of genetics the unavoidable inter-penetration of science, culture, and religion becomes visible. Laboratory researchers cannot separate their daily work from wider cultural interpretations, and the wider culture in this case has elected to interpret genes deterministically. Theologians, who represent the intellectual segment of religious traditions, find themselves simultaneously listening to the bench scientists and the wider cultural cacophony, trying to respond to both. The pressure is increased by the demand from the political sector to establish public policy regarding what is permissible in basic research and resulting medical technology. Society cannot do without either the scientists or the theologians.
See also Behavioral Genetics; Biotechnology; Cloning; DNA; Eugenics; Freedom; Gene Therapy; Genetically Modified Organisms; Genetic Defect; Genetic Determinism; Genetic Engineering; Genetic Testing; Human Genome Project; Memes; Mutation; Naturalism; Nature versus Nurture; Selfish Gene; Sociobiology; Stem Cell Research
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Genetics is the area of biological study concerned with heredity and with the variations between organisms that result from it. It demands an understanding of numerous terms, such as DNA (deoxyribonucleic acid), a molecule in all cells that contains blueprints for genetic inheritance; genes, units of information about particular heritable traits, which are made from DNA; and chromosomes, DNA-containing bodies, located in the cells of most living things, that hold most of the organism's genes. The vocabulary of genetics goes far beyond these three terms, as we shall see, but these are the core concepts. Among the areas in which genetics is applied is forensic science, or the application of science to matters of law—specifically, through "DNA fingerprinting," whereby samples of skin, blood, semen, and other materials can be used to prove or disprove a suspect's innocence. Another fascinating application of genetics is the Human Genome Project, an effort whose goals include the location and identification of every gene in the human body.
HOW IT WORKS
Genetics and Heredity
Genetics and heredity, the subject of another essay in this book, are closely related ideas. Whereas heredity is the transmission of genetic characteristics from ancestor to descendant through the genes, genetics is concerned with hereditary traits passed down from one generation to the next. It is very hard, if not impossible, to separate the two concepts completely, yet the entire body of knowledge encompassed by these topics is so large and so complex that it is best to separate them as much as possible. For this reason, the Heredity essay is concerned with such issues as how traits are passed on and why they appear in a particular generation but not another. That essay addresses the topics of alleles, dominant and recessive genes, and so on. It also briefly discusses the history of studies in areas that encompass genetics, heredity, and the mechanics thereof. In general, the Heredity essay is concerned with the larger patterns of inheritance over the generations, while the present one examines inheritance at a level smaller than the microscopic—that is, from the molecular or biochemical level.
Somatic and Germ Cells
Heredity begins with the cell, the smallest basic unit of all life. The information for heredity is carried within the cell nucleus, which is the control center not only in physical terms (it is usually located near the middle of the cell) but also because it contains the chromosomes. Within these threadlike structures is the genetic information organized in DNA molecules.
There are two basic types of cell in a multicellular organism: somatic, or body, cells, and germ, or reproductive, cells. The somatic cells are the primary components of most organisms, making up everything except some of the the cells in reproductive organs. The somatic cells of humans have 23 pairs of chromosomes, or 46 chromosomes overall, and are thus known as diploid cells. As the cells grow, they reproduce themselves by a process called mitosis, whereby a diploid cell splits to produce new diploids, each of which is a replica of the original. Thus cells grow and are replaced, making possible the formation of specific tissues and organs, such as muscles and nerves. Without mitosis, an organism's cells would not regenerate, resulting not only in cell death but possibly even the death of the entire organism. Mitosis is also the means of reproduction for organisms that reproduce asexually (see Reproduction).
A germ cell, by contrast, undergoes a process of cell division known as meiosis, whereby it becomes a haploid cell—a cell with half the basic number of chromosomes, which for a human would be 23 unpaired chromosomes. The sperm cells in a male and the egg cells in a female are both haploid germ cells: each contains only 23 chromosomes, and each is prepared to form a new diploid by fusion with another haploid. Sperm cells and egg cells are known as gametes, mature male or female germ cells that possess a haploid set of chromosomes and are prepared to form a new diploid by undergoing fusion with a haploid gamete of the opposite sex.
When egg and sperm fuse, they form a zygote, in which the diploid chromosome number is restored, with the zygote possessing the same chromosomes as both the sperm and the egg. This cell carries all the genetic information needed to grow into an embryo and eventually a full-grown human, with the specific traits and attributes passed on by the parents. Not all offspring of the same parents are the same, of course, and this is because the sperm cells and egg cells vary in their genetic codes—that is, in their DNA blueprints.
The DNA Blueprint
To understand genes and their biological function in heredity, it is necessary to understand the chemical makeup and structure of DNA. The complete DNA molecule often is referred to as the blueprint for life, because it carries all the instructions, in the form of genes, for the growth and functioning of organisms. This fundamental molecule is similar in appearance to a spiral staircase, which also is called a double helix. The sides of the DNA ladder are made up of alternate sugar and phosphate molecules, like links in a chain. The rungs, or steps, of DNA are made from a combination of four different chemical bases. Two of these, adenine and guanine, are known as purines, and the other two, cytosine and thymine, are pyrimidines. The four letters designating these bases—A, G, C, and T—are the alphabet of the genetic code, and each rung of the DNA molecule is made up of a combination of two of these letters.
In this genetic code A always combines with T and C with G, to form what is called a base pair. Specific sequences of these base pairs make up the genes. Although a four-letter alphabet may seem rather small for constructing the extensive vocabulary that defines the myriad life-forms on Earth, in practice, the sequences of these base pairs make for almost limitless combinations. For any sequence, there are four possibilities as to the first two letters (AT, TA, CG, or GC) and four more possibilities for the second two letters. Thus, just for a four-letter sequence, there are 16 possibilities, and for each pair of letters added to the sequence, the total is multiplied by four. Given the long strings of base pairs that form DNA sequences, the numbers can be extremely large.
The more complex an organism, from bacteria to humans, the more rungs, or genetic sequences, appear on the ladder. The entire genetic makeup of a human, for example, may contain three billion base pairs, with the average gene unit being 2,000-200,000 base pairs long. Each one of these combinations has a different meaning, providing the code not only for the type of organism but also for specific traits, such as brown hair and blue eyes, dimples, detached earlobes, and so on and on. Except for identical twins, no two humans have exactly the same genetic information.
DNA Replication, Protein Synthesis, and RNA
Genetic information is duplicated during the process of DNA replication, which is initiated by proteins in the cells. To produce identical genetic information during cell mitosis, the DNA hydrogen bonds between the two strands arebroken, splitting the DNA in half lengthwise. This process begins a few hours before the initiation of cell mitosis, and once it is completed, each half of the DNA ladder is capable of forming a new DNA molecule with an identical genetic code. It can do this because of specific chemical catalysts (a substance that enables a chemical reaction without taking part in it) that help synthesize the complementary strand.
Catalysts formed from proteins are known as enzymes, and the functioning of specific cells and organisms is conducted by enzymes synthesized by the cells. Cells contain hundreds of different proteins, complex molecules that make up more than half of all solid body tissues and control most biological processes within and among these tissues. A cell functions in accordance with the particular protein—one of thousands of different types—it contains. It is the genetic base-pair sequence in DNA that determines, or "codes for," the specific arrangement of amino acids to build particular proteins.
Since the sites of protein production lie outside the cell nucleus, coded messages pass from the DNA in the nucleus to the cytoplasm, the material inside the cell that is external to the nucleus. This transfer of messages is achieved by RNA, or ribonucleic acid, and specifically by messenger RNA, or mRNA. Other types of RNA molecules are involved in linking the amino-acids together in a sequence form to shape the protein. (For more about amino acids, proteins, and enzymes, see the respective essays devoted to each subject.)
Once a protein has been created for a specific function, it cannot be changed. This is why the theory of acquired characteristics (the idea that changes in an organism's overall anatomy, as opposed to changes in its DNA, can be passed on to offspring) is a fallacy. People may have genes that make it easier for them to acquire certain traits, such as larger muscles or the ability to play the piano through exercise or practice, respectively, but the traits themselves, if they are acquired during the life of the individual and are not encoded in the DNA, are not heritable.
There is only one way in which changes that take place during the life of an organism can be passed on to its offspring, and that is if those changes are encoded in the organism's DNA. This is known as mutation. Suppose lung cancer develops in a man as a result of smoking; unless a tendency to cancer is already a part of his genetic makeup, he cannot genetically pass the disease on to his unborn children. But if the tobacco has acted as a mutagen, a substance that brings about mutation, it is possible that his DNA can be altered in such a way as to pass on either the tendency toward lung cancer or some other characteristic.
Because DNA is extremely stable chemically, it rarely mutates, or experiences an alteration in its physical structure, during replication. But because there are so many strands of DNA in the world, and so much material in the strands, mutation is bound to happen eventually—and, to an extent, at least, this is a good thing. Mutation is the engine that drives evolution, and a certain amount of genetic variation is necessary if species are to adapt by natural selection to a changing environment. If it were not for mutation, neither humans nor the many millions of other species that exist would ever have appeared.
Mutation often occurs when chromosome segments from two parents physically exchange places with each other during the process of meiosis. This is known as genetic recombination. Genes also can change by mutations in the DNA molecule, which take place when a mutagen alters the chemical or physical makeup of DNA. The mutations that result are of two types, corresponding to the two basic varieties of cell: somatic mutations, which occur solely within the affected individual, and germinal mutations, which happen in the DNA of germ cells, producing altered genes that may be passed on to the next generation.
The odd thing about mutations is that while most of them are harmful, the few that are beneficial are, as we have noted, the driving force behind the evolution of life-forms that successfully adapt to their environments. Thus, while most germinal mutations bring about congenital disorders (birth defects) ranging from physical abnormalities to deficiencies in body or mind to diseases, every once in a while a germinal mutation results in an improvement, such as a change in body coloring that acts as camouflage. If the trait improves an individual organism's chances for survival within a particular environment, it may become a permanent trait of the species, because the offspring with this gene have a greater chance of survival and thus will pass on the trait to succeeding generations. (For more about mutation, see the essay by that title. See also Evolution for a discussion of the role played by mutation and natural selection in the evolution of species.)
The Genetics Revolution
In the modern world genetics plays a part in more dramatic breakthroughs than any other field of biological study. These breakthroughs have an impact in a wide variety of areas, from curing diseases to growing better vegetables to catching criminals. The field of genetics is in the midst of a revolution, and at the center of this exciting (and, to some minds, terrifying) phenomenon is the realm of genetic engineering: the alteration of genetic material by direct intervention in genetic processes. In agriculture, for instance, genes are transplanted from one organism to another to produce what are known as transgenic animals or plants. This approach has been used to reduce the amount of fat in cattle raised for meat or to increase proteins in the milk produced by dairy cattle. Fruits and vegetables also have been genetically engineered so that they do not bruise easily or have a longer shelf life.
Not all of the work in genetics is genetic engineering per se; in the realm of law, for instance, the most important application of genetics is genetic fingerprinting. A genetic fingerprint is a sample of a person's DNA that is detailed enough to distinguish it from the DNA of all others. The genetic fingerprint can be used to identify whether a man is the father of a particular child (i.e., to determine paternity), and it can be applied in the solving of crimes. If biological samples can be obtained from a crime scene—for example, skin under the fingernails of a murder victim, presumably the result of fighting against the assailant in the last few moments of life—it is possible to determine with a high degree of accuracy whether that sample came from a particular suspect. The use of DNA in forensic science is discussed near the conclusion of this essay.
THE REVOLUTION IN MEDICINE.
Some of the biggest strides in genetic engineering and related fields are taking place, not surprisingly, in the realm of medicine. Genetic engineering in the area of health is aimed at understanding the causes of disease and developing treatments for them: for example, recombinant DNA (a DNA sequence from one species that is combined with the DNA of another species) is being used to develop antibiotics, hormones, and other disease-preventing agents. Vaccines also have been genetically re-engineered to trigger an immune response that will protect against specific diseases. One approach is to remove genetic material from a diseased organism, thus making the material weaker and initiating an immune response without causing the disease. (See Immunity and Immunology for more about how vaccines work.)
Gene therapy is another outgrowth of genetics. The idea behind gene therapy is to introduce specific genes into the body either to correct a genetic defect or to enhance the body's capabilities to fight off disease and repair itself. Since many inherited or genetic diseases are caused by the lack of an enzyme or protein, scientists hope one day to treat the unborn child by inserting genes to provide the missing enzyme. (For more about inherited disorders, see the essays Disease, Noninfectious Diseases, and Mutation.)
THE HUMAN GENOME PROJECT.
One of the most exciting developments in genetics is the initiation of the Human Genome Project, designed to provide a complete genetic map outlining the location and function of the 40,000 or so genes that are found in human cells. (A genome is all of the genetic material in the chromosomes of a particular organism.) With the completion of this map, genetic researchers will have easy access to specific genes, to study how the human body works and to develop therapies for diseases. Gene maps for other species of animals also are being developed.
The project had its origins in the 1990s, with the efforts of the United States Department of Energy (DOE) and the National Institutes of Health (NIH). The NIH connection is probably clear enough, but the DOE's involvement at first might seem strange. What, exactly, does genetics have to do with electricity, petroleum, and other concerns of the DOE? The answer is that the DOE grew out of agencies, among them the Atomic Energy Commission (AEC), established soon after the explosion of the two atomic bombs over Japan in 1945. Even at that early date, educated nonscientists understood that the radioactive fallout produced from nuclear weaponry can act as a mutagen; therefore, Congress instructed the AEC to undertake a broad study of genetics and mutation and the possible consequences of exposure to radiation and the chemical by-products of energy production.
Eventually, scientists in the AEC and, later, the DOE recognized that the best way to undertake such a study was to analyze the entire scope of the human genome. The project formally commenced on October 1, 1990, and is scheduled for completion in the middle of the first decade of the twenty-first century. Upon completion, the Human Genome Project will provide a vast store of knowledge and no doubt will lead to the curing of many diseases.
Still, there are many who question the Human Genome Project in particular, and genetic engineering in general, on ethical grounds, fearing that it could give scientists or governments too much power, unleash a Nazi-style eugenics (selective breeding) program, or result in horrible errors, such as the creation of deadly new diseases. In fact, it is impossible to search "genetic engineering" on the World Wide Web without coming across the Web sites of literally dozens and dozens of agencies, activist groups, and individuals opposed to genetic engineering and the mapping of the human genome. For more about the Human Genome Project, genetic engineering, and their opponents, see Genetic Engineering.
Genetics in Forensic Science
Forensic science, as we noted earlier, is the application of science to matters of law. It is based on the idea that a criminal always leaves behind some kind of material evidence that, through careful analysis, can be used to determine the identity of the perpetrator—and to exonerate someone falsely accused. Among those forms of material evidence of interest to forensic scientists working in the field of genetics are blood, semen, hair, saliva, and skin, all of which contain DNA that can be analyzed. In addition, there are areas of forensic science that rely on biological study, though not in the area of genetics: blood typing as well as the analysis of fingerprints or bite marks, both of which have patterns that are as unique to a single individual as DNA is.
One of the first detectives to use science, including biology and medicine, in solving crimes was a fictional character: Sherlock Holmes, whose creator, the British writer Sir Arthur Conan Doyle (1859-1930), happened to be a physician as well. The first full-fledged (and real) police practitioner of forensic science was the French police official Alphonse Bertillon (1853-1914), who developed an identification system that consisted of a photograph and 11 body measurements, including dimensions of the head, arms, legs, feet, hands, and so on, for each individual. Bertillon claimed that the likelihood of two people having the same measurements for all 11 traits was less than one in 250 million. In 1894 fingerprints, which were easier to use and more unique than body measurements, were added to the Bertillon system.
Fingerprints, unlike DNA, are unique to the individual; indeed, identical twins have the same DNA but different fingerprints. Mark Twain (1835-1910) could not have known this in 1894, when he published The Tragedy of Pudd'nhead Wilson, and the Comedy of Those Extraordinary Twins. Nonetheless, the story involves a murder committed by one man and blamed on his twin, who eventually is exonerated on the basis of fingerprint evidence—still a new concept at the time. In some situations, however, fingerprint evidence may be unavailable, and though law-enforcement agencies have developed extraordinary techniques for analyzing nearly invisible (i.e., latent) prints, sometimes this is still not enough.
THE SIMPSON CASE AND THE CONTROVERSY OVER DNA EVIDENCE.
For example, in the infamous murder of Nicole Brown Simpson and Ron Goldman on June 12, 1994, fingerprint evidence would have been ineffective in the case against the suspect, the former football star and actor O. J. Simpson. Since Nicole Simpson was his ex-wife, the appearance of his prints at the scene of her murder in her Los Angeles home could be explained away easily, even though she had taken out a restraining order against her former husband (who she had accused of spousal abuse) some time before the murder. Rather than fingerprints, the prosecution in his murder trial used DNA evidence connecting blood at the crime scene with blood found in Simpson's vehicle. (Some of this blood was apparently his own, since he had mysterious cuts on his hands that he could not explain to police officers.)
A jury found Simpson not guilty on October 3, 1995, and jurors later claimed that the prosecution had failed to make a strong case using DNA evidence. Furthermore, they cited police contamination of the DNA evidence, which had been established in their minds by Simpson's defense team, as a cause for reasonable doubt concerning Simpson's guilt. In fact, assuming that the defense was fully justified in this claim, that would have meant only that the DNA samples would have been less (not more) likely to convict Simpson.
At the same time, a number of legitimate concerns regarding the use of DNA evidence were raised by experts for the defense in the Simpson trial. Samples can become contaminated and thus difficult to read; small samples are difficult for analysts to work with effectively; and results are often open to interpretation. Furthermore, the outcome of the Simpson case illustrates the fact that findings based on DNA evidence are not readily understood by non-specialists, and may not make the best basis for a case-particularly in one so fraught with controversy. The prosecution based its case almost entirely on extremely technical material, explained in excruciating detail by experts who had devoted their lives to studying areas that are far beyond the understanding of the average person. Attempting to wow the jurors with science, the prosecution instead seemed to create the impression that DNA evidence was some sort of hocus-pocus invented to frame an innocent man. Simpson went free, though the jury in a 1996 civil trial (which took a much simpler approach, eschewing complicated DNA testimony) found him guilty.
DNA EVIDENCE SUCCESS STORIES.
Because of the Simpson case, the use of DNA evidence gained something of a bad name. Nonetheless, it has been successful in less high profile cases, beginning in 1986, when English police tracked down a rapist and murderer by collecting blood samples from some 2,000 men. One of them, named Colin Pitchfork, paid another man to provide a sample in his place. This attracted the attention of the police, who tested his DNA and found their man.
Since that time, DNA evidence has been used in more than 24,000 cases and has aided in the conviction of about 700 suspects. The DNA in such cases is not always obtained from a human subject. In the investigation of the May 1992 murder of Denise Johnson in Arizona, a homicide detective found two seed pods from a paloverde tree in the bed of a pickup truck owned by the suspect, Mark Bogan. The accused man admitted having known the victim but denied ever having been near the site where her body was found. It so happened that there was a paloverde tree at the site, and testing showed that the DNA in the pods on his truck bed matched that of the tree itself. Bogan became the first suspect ever convicted by a plant.
On the other hand, in some cases, DNA evidence has cleared a suspect falsely accused. Such was the case with Kerry Kotler, convicted in 1981 for rape, robbery, and burglary and sentenced to 25-50 years in jail. In 1988, Kotler began petitioning for DNA analysis, which subsequently showed that his DNA did not match that of the rapist, who had left a semen sample in the victim's underwear. Kotler was released in December 1992 and in March 1996 was awarded $1.5 million in damages for his wrongful imprisonment. The story does not end there, however. Kotler's case turned out to be one of the more bizarre in the annals of forensic DNA testing. Perhaps he did not commit the first rape, but a month after he received the damage award, he was on his way back to prison for the August 1995 rape of another victim. This time prosecutors showed that Kotler's semen matched samples taken from his victim's clothing—and to prove their case, they used DNA testing.
WHERE TO LEARN MORE
Department of Energy Human Genome Program (Web site). <http://www.ornl.gov/hgmis/>.
Fridell, Ron. DNA Fingerprinting: The Ultimate Identity. New York: Franklin Watts, 2001.
Genetics Education Center, University of Kansas Medical Center (Web site). <http://www.kumc.edu/gec/>.
Henig, Robin Marantz. The Monk in the Garden: The Lost and Found Genius of Gregor Mendel, the Father of Genetics. Boston: Houghton Mifflin, 2000.
Lerner, K. Lee, and Brenda Wilmoth Lee. World of Genetics. Detroit: Gale Group, 2002.
National Human Genome Research Institute (Web site). <http://www.nhgri.nih.gov>.
Schwartz, Jeffrey H. Sudden Origins: Fossils, Genes, and the Emergence of Species. New York: John Wiley and Sons, 1999.
Tudge, Colin. The Impact of the Gene: From Mendel's Peas to Designer Babies. New York: Hill and Wang, 2001.
Virtual Library on Genetics, Oak Ridge National Laboratory (Web site). <http://www.ornl.gov/TechResources/Human_Genome/genetics.html>.
Sometimes known as acquired characters or Lamarckism, after one of its leading proponents, the French natural philosopher Jean Baptiste de Lamarck (1744-1829), the theory of acquired characteristics is a fallacy that should not be confused with mutation. Acquired characteristics theory maintains that changes that occur in an organism's overall anatomy (as opposed to changes in its DNA) can be passed on to offspring.
Organic compounds made of carbon, hydrogen, oxygen, nitrogen, and (in some cases) sulfur bonded in characteristic formations. Strings of amino acids make up proteins.
A pair of chemicals that form the "rungs" on a DNA molecule, which has the shape of a spiral staircase. A base pair always consists of a type of chemical called a purine on one side and a chemical termed a pyrimidine on the other. This means that DNA base pairs always consist of adenine linked with thymine and guanine with cytosine.
The area of the biological sciences concerned with the chemical substances and processes in organisms.
See somatic cell.
A DNA-containing body, located in the cells of most living things, that holds most of the organism's genes.
An abnormality of structure or function or adisease that is present at birth. Congenital disorders also are called birth defects.
The material inside a cell that is external to the nucleus.
A term for a cell that has the basic number of doubled chromosome cells. In humans, somatic cells, which are diploid cells, have 23 pairs of chromosomes, for a total of 46 chromosomes.
Deoxyribonucleic acid, a molecule in all cells, and many viruses, that contains genetic codes for inheritance.
In genetics, a term for a trait that can manifest in the offspring when inherited from only one parent. Its opposite is recessive.
A protein material that speeds up chemical reactions in the bodies of plants and animals without itself taking part in or being consumed by those reactions.
The application of science to matters of law and legal or police procedure.
A mature male or female germ cell that possesses a haploid set of chromosomes and is prepared to form a new diploid by undergoing fusion with a haploid gamete of the opposite sex.
A unit of information about a particular heritable trait. Usually stored on chromosomes, genes contain specifications for the structure of a particular polypeptide or protein.
The alteration of genetic material by direct intervention in genetic processes.
A sample of a person's DNA that is detailed enough to distinguish it from all other people's DNA.
A process whereby chromosome segments from two parents physically exchange places with each other during the process of meiosis. This is one of the ways that mutation occurs.
The area of biological study concerned with heredity, with hereditary traits passed down from one generation to the next through the genes, and with the variations between organisms that result from heredity.
All of the genetic material in the chromosomes of a particular organism.
One of two basic types of cells in a multicellular organism. In contrast to somatic, or body, cells, germ cells are involved in reproduction.
A mutation that occurs in the germ cells, meaning that the mutation can be passed on to the organism's offspring.
A term for a cell that has half the number of chromosome cells that appear in a diploid, or somatic, cell. In humans, germ cells, which are haploidcells, have 23 unpaired chromosomes, as opposed to the 23 paired chromosomes (46 overall) that appear in a somatic cell.
The transmission of genetic characteristics from ancestor to descendant through the genes.
Capable of being inherited.
The process of cell division that produces haploid genetic material. Compare with mitosis.
A process of cell division that produces diploid cells. Compare with meiosis.
Messenger ribonucleic acid, a molecule of RNA that carries the genetic information for producing proteins.
A chemical or physical factor that increases the rate of mutation.
Alteration in the physical structure of an organism's DNA, resulting in a genetic change that can be inherited.
The process whereby some organisms thrive and others perish, depending on their degree of adaptation to a particular environment.
Acids, including DNA and RNA, that are made up of nucleotide chains.
A compound formed from one of several types of sugar joined with a base of purine or pyrimidine (see base pair ) and a phosphate group. Nucleotides are the basis for nucleic acids.
The control center of a cell, where DNA is stored.
A group of between 10 and 50 amino acids.
Large molecules built from long chains of 50 or more amino acids. Proteins serve the functions of promoting normal growth, repairing damaged tissue, contributing to the body's immune system, and making enzymes.
In genetics, a term for a trait that can manifest in the offspring only if it is inherited from both parents. Its opposite is dominant.
See germ cell.
Ribonucleic acid, a molecule translated from DNA in the cell nucleus that directs protein synthesis in the cytoplasm. See also mRNA.
One of two basic types of cells in a multicellular organism. In contrast to germ cells, somatic cells (also known as body cells ) do not play a part in reproduction; rather, they make up the tissues, organs, and other parts of the organism.
A mutation that occurs in cells other than the reproductive, or sex, cells. These mutations, as contrasted with germinal mutations, cannot be transmitted to the next generation.
To manufacture chemically, as in the body.
A mutation in which chromosomes exchange parts.
A diploid cell formed by the fusion of two gametes.
Genetics is the branch of biology concerned with the science of heredity, or the transfer of specific characteristics from one generation to the next. Genetics focuses primarily on genes, coded units found along the DNA molecules of the chromosomes, housed by the cell nucleus. Together, genes make up the blueprints that determine the entire development of the species of organisms down to specific traits, such as the color of eyes and hair. Geneticists are concerned with three primary areas of gene study: how genes are expressed and regulated in the cell, how genes are copied and passed on to successive generations, and what are the genetic basis for differences between the species. Although the science of genetics dates back at least to the nineteenth century, little was known about the exact biological makeup of genes until the 1940s. Since that time, genetics has moved to the forefront of biological research. Scientists are now on the verge of identifying the location and function of every gene in the entire human genome . The result will not only be a greater understanding of the human body, but new insights into the origins of disease and the formulation of possible treatments and cures.
The history of genetics
Although humans have known about inheritance for thousands of years, the first scientific evidence for the existence of genes came in 1866, when the Austrian monk and scientist Gregor Mendel published the results of a study of hybridization of plants—the combining of two individual species with different genetic make-ups to produce a new individual. Working with pea plants with specific characteristics such as height (tall and short) and color (green and yellow), Mendel bred one type of plant for several successive generations. He found that certain characteristics appeared in the next generation in a regular pattern. From these observations, he deduced that the plants inherited a specific biological unit (which he called factors (now called alleles ), genes determining different forms of a single characteristic) from each parent. Mendel also noted that when factors or alleles pair up, one is dominant (which means it determines the trait, like tallness) while the other is recessive (which means it has no bearing on the trait). It is now understood that alleles may be single genes or sets of genes working together, each contributing to the final form of a physical characteristic (multiple allelism).
The period of classical genetics, in which researchers had no knowledge of the chemical constituents in cells that determine heredity, lasted well into the
twentieth century. However, several advances made during that time contributed to the growth of genetics. In the eighteenth century, scientists used the relatively new technology of the microscope to discover the existence of cells, the basic structures in all living organisms. By the middle of the nineteenth century, they had discovered that cells reproduce by dividing.
Although Mendel laid the foundation of genetics, his work began to take on true significance in 1903 when Theodore Boveri and Walter Sutton independently proposed a chromosomal theory of inheritance. They discovered that chromosomes during gamete production behave like the so-called Mendel's particles behave. In 1910, Thomas Hunt Morgan (1866–1946) confirmed the existence of chromosomes through experiments with fruit flies . He also discovered a unique pair of chromosomes called the sex chromosomes, which determined the sex of offspring. Morgan deduced that specific genes reside on chromosomes from his observation that an X-shaped chromosome was always present in flies that had white eyes. A later discovery showed that chromosomes could mutate or change structurally, resulting in a change in characteristics which could be passed on to the next generation.
More than three decades passed before scientists began to delve into the specific molecular and chemical structures that make up chromosomes. In the 1940s, a research team led by Oswald Avery (1877–1955) discovered that deoxyribonucleic acid (DNA) was responsible for transformation of non-pathogenic bacteria into pathogenic ones. The final proof that DNA was the specific molecule that carries genetic information was made by Alfred Hershey and Martha Chase in 1952. They used radioactive label to differentiate between viral protein and DNA, proving that over 80% of viral DNA entered bacterial cell causing infection , while protein did not cause infection.
The most important discovery in genetics occurred in 1953, when James Watson and Francis Crick solved the mystery of the exact structure of DNA. The two scientists used chemical analyses and x-ray diffraction studies performed by other scientists to uncover the specific structure and chemical arrangement of DNA. X-ray diffraction is a procedure in which parallel x-ray beams are diffracted by atoms in patterns that reveal the atoms' atomic weight and spatial arrangement. A month after their double-helix model of DNA appeared in scientific journals, the two scientists showed how DNA replicated. Armed with these new discoveries, geneticists embarked on the modern era of genetics, including efforts like genetic engineering , gene therapy , and a massive project to determine the exact location and function of all of the more than 100,000 genes that make up the human genome.
The biology of genetics
Genetic information is contained in the chromosomes, threadlike structures composed of DNA, and present in the nuclei of all cell types and are passed to daughter cells during cell division . Multicellular organisms contain two types of cells—body cells (or somatic cells) and germ cells (or reproductive cells). Germ cells are the ones that pass on the genetic information to the progeny. In contrast to somatic cells that contain dual copies of chromosomes in each cell, germ cells replicate through a process called meiosis , which ensures that the germ cells have only a single set of chromosomes, a condition called haploidy (designated as n). The somatic cells of humans have 23 pairs of chromosomes (46 chromosomes overall), a condition known as diploid (or 2n). Through the process of meiosis, a new cell, called a haploid gamete, is created with only 23 chromosomes: this is either the sperm cell of the father or the egg cell of the mother. The fusion of egg and sperm restores the diploid chromosome number in the zygote. This cell carries all the genetic information needed to grow into an embryo and eventually a full grown human with the specific traits and attributes passed on by the parents. Offspring of the same parents differ because the sperm cells and egg cells vary in their gene sequences , due to random recombination.
The somatic, or body cells are the primary components of functioning organisms. The genetic information in these cells is passed on through a process of cell division called mitosis . Unlike meiosis, mitosis is designed to transfer the identical number of chromosomes during cell regeneration or renewal. This is how cells grow and are replaced in exact replicas to form specific tissues and organs, such as muscles and nerves. Without mitosis, an organism's cells would not regenerate, resulting not only in cell death , but possible death of the entire organism . (It is important to note that some organisms reproduce asexually by mitosis alone.)
The genetic code
To understand genes and their biological function in heredity, it is necessary to understand the chemical makeup and structure of DNA. Although some viruses carry their genetic information in the form of ribonucleic acid (RNA) , most higher life forms carry genetic information in the form of DNA, the molecule that makes up chromosomes.
The complete DNA molecule is often referred to as the blueprint for life because it carries all the instructions, in the formation of genes, for the growth and functioning of most organisms. This fundamental molecule is similar in appearance to a spiral staircase, which is also called a double helix . The sides of the DNA double helix ladder are made up of alternate sugar and phosphate molecules, like links in a chain. The rungs, or steps, of DNA are made from a combination of four nitrogen-containing bases—two purines (adenine [A] and guanine [G]) and two pyrimidines (cytosine [C] and thymine [T]). The four letters designating these bases (A, G, C, and T) are the alphabet of the genetic code. Each rung of the DNA molecule is contains a combination of two of these letters, one jutting out from each side. In this genetic code, A always combines with T, and C with G to make what is called a base pair. Specific sequences of these base pairs, which are bonded together by atoms of hydrogen , make up the genes.
While a four-letter alphabet may seem rather small for constructing the comprehensive vocabulary that describes and determines the myriad life forms on Earth , the sequences or order of these base pairs are nearly limitless. For example, various sequences or rungs that make up a simple six base gene could be ATCGGC, or TAATCG, or AGCGTA, or ATTACG, and so on. Each one of these combinations has a different meaning. Different sequences provide the code not only for the type of organism, but also for specific traits like brown hair and blue eyes. The more complex an organism, from bacteria to humans, the more rungs or genetic sequences appear on the ladder. The entire genetic makeup of a human, for example, may contain 120 million base pairs, with the average gene unit being 2,000 to 200,000 base pairs long. Except for identical twins, no two humans have exactly the same genetic information.
Genetic information is duplicated during the process of DNA replication , which begins a few hours before the initiation of cell division (mitosis). To produce identical genetic information during mitosis, the hydrogen bonds holding together the two halves of the DNA ladder unzip, in presence of proteins called helicases, to expose single strands of DNA. These old strands act as templates to make new DNA molecules. Replication is initiated by this separation of DNA, and requires short DNA fragments (primers) to start synthesis of a new DNA strand by specific cellular enzymes called DNA polymerases. DNA rarely mutates during replication, as the proofreading and "repair" enzymes make sure that any errors are quickly repaired to protect the accuracy of the genetic information. Once completed, each new half of the DNA ladder has the identical information as the old one. This is achieved by the fact that T always combines with A and C with G, therefore if the template had a sequence ATGCTG the newly made second strand will be TACGAC. When cell mitosis is completed, each new cell contains an exact replica of the DNA.
Cells contain hundreds of different proteins and its functions are dependent on which of the thousands of types of different proteins it contains. Proteins are made up of chains of amino acids. The arrangement of the amino acids to build specific proteins is determined by the basepair sequence contained or encoded in DNA. This genetic information has to be converted to proteins building over half of all solid body tissues and control most biological processes within and among these tissues. This is achieved by using the genetic code, which is a set of 64 triplets of bases (called codons ) corresponding to each amino acid and the initiation and termination signals for protein synthesis.
As the sites of protein production lie outside the cell nucleus, the instructions for making them have to be transported out of the nucleus. The messenger that carries these instructions is messenger RNA, or mRNA (a single stranded molecule that has a mirror image of the base pairs on the DNA). mRNA is made in the nucleus during a process called transcription and a single molecule of RNA carries instructions for making only one protein. After being exported out of the nucleus it is transported to ribosomes , which are the protein factories in the cell. In ribosomes the information from mRNA is decoded to produce a protein. This process is called translation. The flow of information is only one way from DNA to RNA and to protein. Therefore characteristics acquired during an organism's life, such as larger muscles or the ability to play the piano, cannot be inherited. However, people may have genes that make it easier for them to acquire these traits through exercise or practice.
Dominant and recessive traits
The expression of the products of genes is not equal, and some genes will override others in expressing themselves as an inherited characteristic. The offspring of organisms that reproduce sexually contain a set of chromosome pairs, half from the father and half from the mother. However, normally people do not have one blue eye and one brown eye, or half brown hair and half blond hair because most genetic traits are the result of the expression of either the dominant or the recessive genes. If a dominant and a recessive gene appear together (the heterozygous condition), the dominant will always win, producing the trait it is coded for. The only time a recessive trait (such as the one for blond hair) expresses itself is when two recessive genes are present (the homozygous condition). As a result, parents with heterozygous genes for brown hair could produce a child with blond hair if the child inherits two recessive blond-hair genes from the parents. The genes residing in the chromosome's DNA can also be present in alternative forms called alleles. It is important to note that some characteristics are a result of presence of various alleles, e.g. pink snapdragon flowers or blood types.
This hereditary law also holds true for genetic diseases. Neither parent may show signs of a genetic disease, caused by a defective gene, but they can pass the double-recessive combination on to their children. Some genetic diseases are dominant and others are recessive. Dominant genetic defects are more common because it only takes one parent to pass on a defective allele. A recessive genetic defect requires both parents to pass on the recessive allele that causes the disease. A few inherited diseases (such as Down syndrome ) are caused by abnormalities in the number of chromosomes, where the offspring has 47 chromosomes instead of the normal 46.
Genetic recombination and mutations
The DNA molecule is extremely stable, ensuring that offspring have the same traits and attributes that will enable them to survive as well as their parents. However, a certain amount of genetic variation is necessary if species are to adapt by natural selection to a changing environment. Often, this change in genetic material occurs when chromosome segments from the parents physically exchange segments with each other during the process of meiosis. This is known as cross over or intrinsic recombination.
Genes can also change by mutations on the DNA molecule, which occur when a mutagen alters the chemical or physical makeup of DNA. Mutagens include ultraviolet light and certain chemicals. Genetic mutations in somatic (body) cells result in malfunctioning cells or a mutant organism. These mutations result from a change in the base pairs on the DNA, which can alter cell functions and even give rise to different traits. Somatic cell mutations can result in disfigurement, disease, and other biological problems within an organism. These mutations occur solely within the affected individual.
When mutations occur in the DNA of germ (reproductive) cells, these altered genes can be passed on to the next generation. A germ cell mutation can be harmful or result in an improvement, such as a change in body coloring that acts as camouflage. If the trait improves an individual organism's chances for survival within a particular environment, it is more likely to become a permanent trait of the species because the offspring with this gene would have a greater chance to survive and pass on the trait to succeeding generations.
Mutations are generally classified into two groups, spontaneous mutations and induced mutations. Spontaneous mutations occur naturally from errors in coding during DNA replication. Induced mutations come from outside influences called environmental factors. For example, certain forms of radiation can damage DNA and cause mutations. A common example of this type of mutating agent is the ultraviolet rays of the sun , which can cause skin cancer in some people who are exposed to intense sunlight over long periods of time. Other mutations can occur due to exposure to man-made chemicals. These types of mutations modify or change the chemical structure of base pairs.
Population genetics is the branch of genetics that focuses on the occurrence and interactions of genes in specific populations of organisms. One of its primary concerns is evolution , or how genes change from one generation to the next. By using mathematical calculations that involve an interbreeding population's gene pool (the total genetic information present in the individuals within the species), population geneticists delve into why similar species vary among different populations that may, for example, be separated by physical boundaries such as bodies of water or mountains .
As outlined in the previous section, genetic mutations may cause changes in a population if the mutation occurs in the germ cells. Many scientists consider mutation to be the primary cause of genetic change in successive generations. However, population geneticists also study three other factors involved in genetic change or evolution: migration , genetic drift, and natural selection.
Migration occurs when individuals within a species move from one population to another, carrying their genetic makeup with them. Genetic drift is a natural mechanism for genetic change in which specific genetic traits coded in alleles (alternate states of functioning for the same gene) may change by chance often in a situation where organisms are isolated, as on an island .
Natural selection, a theory first proposed by Charles Darwin in 1858, is a process that occurs over successive generations. The theory states that genetic changes that enhance survival for a species will come to the forefront over successive generations because the gene carriers are better fit to survive and are more likely reproduce, thus establishing a new gene pool, and eventually, perhaps, an entirely new species. One proposed mechanism of natural selection is gradualism, which predicts very slow and steady accumulation of beneficial genes. Punctuated equilibrium , in contrast, depicts natural selection as occurring in brief, but accelerated periods of "survival of the fittest" with lengthy periods of relative stagnation of genetic change in populations. Some scientists hold that both processes occur and have occurred.
Genetics and the golden age of biology
More than any other biological discipline, genetics is responsible for the most dramatic breakthroughs in biology and medicine today. Scientists are rapidly advancing in their ability to engineer genetic material to achieve specific characteristics in plants and animals. The primary way to genetically engineer DNA is called gene cloning, in which a segment of one DNA molecule is removed and then inserted, into another DNA molecule. This process takes advantage of restriction enzymes to cut DNA into fragments of different lengths and ligase to re-create new molecules. Restriction enzymes act as molecular scissors, cutting larger molecules (like DNA) at specific sites. The ends of these fragments are "sticky" in that they have an affinity for complimentary ends of other DNA fragments. DNA ligase acts as a glue to join the ends of the two molecules together. This approach has applications in agriculture and medicine.
In agriculture, genetic engineering is used to produce transgenic animals or plants, in which genes are transferred from one organism to another. This approach has been used to reduce the amount of fat in cattle raised for meat, or to increase proteins in the milk of dairy cattle that favor cheese making. Fruits and vegetables have also been genetically engineered so they do not bruise as easily, or so they have a longer shelf life. On the other hand, in medicine, genetic engineering provided great advancements in production of antibiotics , hormones , vaccines, understanding disease mechanisms and in therapy. Gene therapy is currently being developed and used as it provides the opportunity to introduce specific genes into the body to either correct a genetic defect or to enhance the body's capabilities to fight off disease and repair itself. Because many inherited or genetic diseases are caused by the lack of an enzyme or protein, scientists hope to one day treat the unborn by inserting genes to provide the missing enzyme.
Genetic fingerprinting (DNA typing) is based on each individual's unique genetic code. To identify parentage, diagnose inherited diseases in prenatal laboratories or the presence of someone at a crime, scientists use molecular biology techniques such as DNA fingerprinting by applying restriction fragment length polymorphisms (RFLPs) analysis (identifying the characteristic patterns in DNA cut with the restriction enzymes), microsattelite analysis (looking at the small specific DNA sequences), DNA hybridization, DNA sequencing or polymerase chain reaction (PCR ). Development of PCR allows to analyse small amounts of DNA acquired from hair, semen, blood, fingernail fragments, or fetal cells by utilizing DNA polymerase enzyme (the same enzyme used naturally by cells in mitosis) to create identical copies of a DNA molecules from small samples.
One of the most exciting recent developments in genetics is the initiation of the Human Genome Project (HGP). This project is designed to provide a complete genetic road map outlining the location and function of the 100,000 or so genes found in human cells encoded in over three billion bases. The first human genome draft sequences were published in February 2001 by the Celera company and the HGP consortium in the journals Science and Nature, respectively. As a result, genetic researchers will have easy access to specific genes to study how the human body works and to develop therapies for diseases. Gene maps for other species of animals are also being developed.
Future of genetics
Full sequencing of many bacterial genomes, yeast , Caenorhabditis elegans, Drosophila, mouse, and human genomes has brought about a new era in genetics, and a development of a new area—genomics. Availability of full DNA sequences of multiple organisms allows the comparative analysis (comparative genetics) of genomes allowing gene identification, finding of regulatory sequences and tracing evolution.
Genetic analysis proved very successful in Mendelian diseases. New challenges for genetics are the studies of common complex diseases such as asthma , obesity orhypertension . These diseases are caused by interaction of multiple genes and also environment, making their analysis even more difficult. Geneticists analyze DNA sequence to correlate any changes with the disease (association studies). Small fragments of repetitive DNA sequence (microsatellites) or single nucleotide polymorphisms (SNPs) are analyzed. Such studies require analysis of large control (healthy) population in addition to the affected group before any conclusions can be made. Solving of the puzzle of complex traits is going to be possible by combining molecular genetics, biostatistics, further clinical and computational/bioinformatical analysis.
Ethical questions and the future of genetics
Despite the promise of genetics research, many ethical and philosophical questions arise. Many of the concerns about this area of research focus on the increasing ability to manipulate genes. There is a fear that the results will not always be beneficial. For example, some fear that a genetically re-engineered virus could turn out to be extremely virulent, or deadly, and may spread if there is no way to stop it.
Another area of concern is the genetic engineering of human traits and qualities. The goal is to produce people with specific traits such as better health, improved looks, or even high intelligence. While these traits may seem to be desirable on the surface, the concern arises about who will decide exactly what traits are to be engineered into human offspring, and whether everyone will have equal access to an expensive technology. Some fear that the result could be domination by a particular socioeconomic group.
Despite these fears and concerns, genetic research continues. In an effort to ensure that the science is not abused in ways harmful to society, governments in the United States and abroad have created panels and organizations to oversee genetic research. For the most part, international committees composed of scientists and ethical experts state that the benefits of genetic research for medicine and agriculture far outweigh the possible abuses.
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. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
—Any of two or more alternative forms of a gene that occupy the same location on a chromosome.
- Amino acid
—A chemical unit that makes up part of the DNA molecule. There are four bases: adenine (A) and guanine (G), which are purines, and cytosine (C) and thymine (T), which are pyrimidines.
—he structures that carry genetic information in the form of DNA. Chromosomes are located within every cell and are responsible for directing the development and functioning of all the cells in the body.
—Deoxyribonucleic acid; the genetic material in a cell. Chromosomes are made of DNA.
- Dominant (dominant gene)
—An allele of a gene that results in a visible phenotype if expressed in a heterozygote.
—A discrete unit of inheritance, represented by a portion of DNA located on a chromosome. The gene is a code for the production of a specific kind of protein or RNA molecule, and therefore for a specific inherited characteristic.
- Genetic recombination
—New configurations produced when two DNA molecules are broken and rejoined together during meiosis.
—Characteristics passed on from parents to offspring.
—Two different forms of the same allele pair on the chromosome.
—Two identical forms of the same allele pair on the chromosome.
—The process of cell division in germ or reproductive cells, producing haploid genetic material.
—The process of cell division in somatic, or body, cells, producing no change in genetic material.
—Macromolecules made up of long sequences of amino acids. They make up the dry weight of most cells and are involved in structures, hormones, and enzymes in muscle contraction, immunological response, and many other essential life functions.
—Refers to the state or genetic trait that only can express itself when two genes, one from both parents, are present and coded for the trait, but will not express itself when paired with a dominant gene. (See Dominant; Allele)
- Ribonucleic acid
—RNA; the molecule translated from DNA in the nucleus that directs protein synthesis in the cytoplasm; it is also the genetic material of many viruses.
—The process of synthesizing RNA from DNA.
Genetics is the branch of biology that deals with heredity—the passing of characteristics (traits) from parents to offspring. The genetics of aging deals with the studies of heredity for traits related to aging, such as life span, age at menopause, age at onset of specific diseases in late life (Alzheimer's disease, prostate cancer, etc.), rate of aging (estimated through tests for biological age), rate-of-change traits, and biomarkers of aging. In practice, most studies are focused on life span, because other reliable markers of aging are lacking or less convenient to use. Therefore, the genetics of aging is closely related to the biology of life span.
Genetics is also the study of the fundamental chemical units of heredity, called genes. A gene is a segment of deoxyribonucleic acid (DNA), which carries coded hereditary information. Genes are made up of four types of nitrogenous compounds (called bases ) known by their first initials: A (adenine), C (cytosine), G (guanine), and T (thymine). The sequence, or code, is the order in which these four bases link up with the sugar deoxyribose and phosphate to form the DNA molecule. To determine the entire sequence of the three billion bases that make up human DNA (the human genome), the U.S. Human Genome Project was initiated in 1990. On 26 June 2000, Celera Genomics announced that it had identified, in general, the sequence of the human genome (with partial use of the Human Genome Project data). The complete sequence is expected to be known by 2003. Many researchers believe that the completion of the Human Genome Project will create a revolution in the identification of the genes involved in the aging process.
The total number of genes in the human genome is still unknown, with estimates around forty-two thousand genes. By comparison, the fruit fly, Drosophila melanogaster, has 13,600 genes, while the bacteria Escherichia coli has only 4,300 genes. The number of gerontogenes (genes involved in the aging process) remains to be established, but there are no doubts of their existence. For example, in humans, one of the forms of a gene coding for apolipoprotein E (ApoE ε 2) is associated with exceptional longevity and decreased susceptibility to Alzheimer's disease.
Each gene occupies a specific position (locus) on a thread-like structure called a chromosome. A chromosome is the linear end-to-end arrangement of genes and other DNA, usually with associated protein and ribonucleic acid (RNA). Chromosomes can be seen in cells with an ordinary microscope. Every human cell (except egg and sperm cells) contains two sets of twenty-three chromosomes—one set from the mother and another set from the father, for a total of forty-six chromosomes. However, the proportion of aberrant cells with "wrong" numbers of chromosomes increases with age, and this may cause cancer and other diseases in later life.
Genetics also involves the study of the mechanism of gene action —the way in which genes produce their effect on an organism by influencing biochemical processes during development and aging. The first steps of gene action are well understood in molecular genetics and can be summarized by a simple schema: DNA → RNA → protein. According to this schema, genetic information is first transmitted from DNA to RNA (first arrow corresponding to transcription process), and then from RNA to protein (second arrow corresponding to translation process). In other words, the DNA genetic code ultimately determines the structure (amino acid sequence) of proteins. However, the final steps of gene action in shaping the complex structural, functional, and behavioral traits of an organism, as well as species life span and aging patterns, remain to be understood.
Although genes determine the features an organism may develop, the features that actually develop depend upon the complex interaction between genes and their environment, called gene-environment interaction. Gene-environment interactions are important because genes produce their effects in an indirect way (through proteins), and the ultimate outcome of gene action may be different in different circumstances. It is recognized from the effects of diet restriction on mice and other species that gene-environment interactions can greatly modify life span and the rate of aging. Understanding interactions between genes and a restricted diet is important because caloric restriction is known to be the most effective way to extend life span and delay age-related diseases in mammals.
Many of the genes within a given cell are inactive (repressed) much, or even all, of the time. Different genes can be switched on or off depending on cell specialization (differentiation)—a phenomenon called differential gene expression. Gene expression may change over time within a given cell during development and aging. Changes in differential gene expression are vitally important for cell differentiation during early child development, but they may persist further in later life and become the driving force of the aging process. Some researchers believe that pharmacological control over differential gene expression in later life may be a feasible approach in the future to slow down the aging process and to increase life span.
Occasionally, changes may occur in a gene or in a chromosome set of a cell, making it different from the original (wild) type. The process that produces such changes is called mutation. This term is also used to label the gene or chromosome set that results from mutation process. In many cases, mutations are caused by DNA damage, including oxidative damage or radiation damage (by ultraviolet light, ionizing radiation, or heat). Every time cells divide the risk of mutation increases. This is because mistakes (copy errors) are likely to occur during copying (replication) of a huge DNA molecule in a dividing cell. Accumulation of deleterious mutations with age is one of the possible mechanisms of aging.
Genetics also involves the study of how the aging and life span of progeny depend on parental characteristics, such as parental life span and parental age at conception. Familial resemblance in life span between parents and children is very small when parents live shorter lives (30–70 years) and very strong in the case of longer-lived parents, suggesting an unusual nonlinear pattern of life span inheritance. Also, children conceived by fathers at an older age have more inborn mutations and may be at higher risk of Alzheimer's disease and prostate cancer in later life. Daughters conceived by fathers age forty-five and older live shorter lives, on average, while sons seems to be unaffected in this regard, suggesting the possible role of mutations on the paternal X chromosome (inherited by daughters only) in the aging process.
Leonid A. Gavrilov Natalia S. Gavrilova
See also Evolution of Aging; Genetics: Gene-Environment Interaction; Genetics: Gene Expression; Genetics: Longevity Assurance; Genetics: Parental Influence; Genetics: Tumor Suppression; Longevity: Selection; Mutation.
Arking, R. Biology of Aging: Observations and Principles, 2d ed. Sunderland, Mass.: Sinauer Associates, 1998.
Carnes, B. A.; Olshansky, S. J.; Gavrilov, L. A.; Gavrilova, N. S.; and Grahn, D. "Human Longevity: Nature vs. Nurture—Fact or Fiction." Perspectives in Biology and Medicine 42 (1999): 422–441.
Finch, C. E., and Tanzi, R. E. "Genetics of Aging." Science 278 (1997): 407–411.
Gavrilov, L. A., and Gavrilova, N. S. The Biology of Life Span: A Quantitative Approach. New York: Harwood Academic Publisher, 1991.
Gavrilov, L. A., and Gavrilova, N. S. "Human Longevity and Parental Age at Conception." In Sex and Longevity: Sexuality, Gender, Reproduction, Parenthood. Edited by J.-M. Robine, et al. Berlin: Springer-Verlag, 2000. Pages 7–31.
Gavrilova, N. S., et al. "Evolution, Mutations and Human Longevity: European Royal and Noble Families." Human Biology 70 (1998): 799–804.
Martin, G. M.; Austad, S. N.; and Johnson, T. E. "Genetic Analysis of Ageing: Role of Oxidative Damage and Environmental Stresses." Nature Genetics 13 (1996): 25–34.
Vogel, F., and Motulsky, A. G. Human Genetics. Problems and Approaches, 3d ed. Berlin: Springer-Verlag, 1997.
GENETICS. Since the first efforts were made to cultivate plants, humans have employed genetics to breed crops with improved taste, hardiness, or yield. The long history of genetics and nutrition can be felt even today, and permeates many aspects of our daily life. Home gardeners can purchase seeds that will grow in particular soils, produce fruit at various times of the year, or grow in sunshine or shade. Local supermarkets sell supersweet varieties of corn and fruits such as the tangelo, made from crossing grapefruits with tangerines. The "Green Revolution," which began with the identification of a high-yield strain of wheat, has resulted in dramatic increases in food production around the world. With the advent of genetic engineering, new, disease resistant crops have been developed, with the promise of reducing requirements for pesticide use.
Plants are not the only organism to be subjected to genetic breeding programs by humans. Yeast strains for baking bread or producing alcoholic beverages have been cultured for centuries. Meatier turkeys and cows that give more milk are the product of animal breeding efforts. Some have argued that the genetic manipulation of foodstuffs has gone too far, emphasizing crops that can withstand long storage times, transportation to markets, and handling by the consumer over any selection for flavor. Others worry that genetic engineering gives us unprecedented, and perhaps dangerous, opportunities to mix and match desired traits. It is nevertheless apparent that genetics has had an enormous impact upon society.
What is genetics? Simply put, genetics is the study of hereditary variation. This variation, in essence, is the diversity of life as it exists in all its forms on earth. For example, there are perhaps some 300,000 different species of flowering plants. What makes each of these plants different from one another? Perhaps even more amazing than this variation between species, there are astounding levels of variation that can be found even within a species. There are, for example, some 6,000 different varieties of apples alone. Genetics aims to understand how this variation occurs between species as well as within species. The term "phenotype" is used to describe any differences that can be observed or measured. For example, the possession of yellow kernels is a phenotype of a particular strain of corn, which distinguishes it from strains that possess white kernels. The two may have phenotypes in common (e.g., they both have white flowers or are supersweet) in addition to the differing phenotype of yellow and white kernels. Genetics examines the ground rules regarding how these phenotypes are passed on, or inherited, from one generation to the next.
Gregor Mendel, the Father of Genetics
While genetic breeding has been practiced for many hundreds of years, the true science of genetics began with Gregor Mendel, an Austrian monk who published his seminal work in the mid-1800s. At the time, genes had not been identified; indeed, the term itself would not be coined until 1909. How traits could be inherited from one generation to another was entirely unclear. Charles Darwin himself proposed the pangenesis theory, in which traits from the parents are passed to their children in a process that "blends" them together. In this theory, children represent a melding of the two parental sets of traits. They in turn would pass their traits on to their children, further blending together the traits of their respective parents. This model of how genetics operates can be contrasted with the particulate theory, in which traits are retained on small particles passed from one generation to the next. While Darwin's model would seem to be consistent with what we can observe in our own children, Mendel's carefully performed and insightful experiments clearly supported the particulate theory, and laid down the basic principles of the inheritance of phenotypes.
Mendel discovered his principles working with pea plants, which were raised not only for their experimental value but also as a food source for the monastery. Mendel's seminal idea was to identify clearly defined and distinct traits among these plants, and determine how these phenotypes were passed from one generation to the next. For example, Mendel identified plants that possessed either white flowers or purple flowers, but not both. He then crossed these two different variants with one another (the "parental," or P0 generation), and examined the flower color of the resulting progeny plants in the filial, or F1, generation. If the blending theory were correct, one might expect pink flowers to be produced in the F1 plants. Instead, Mendel obtained only purple flowered plants. If these F1 purple-flowered plants were then interbred with one another, producing an F2 generation of plants, Mendel saw once again pea plants with white flowers. Thus, even though this particular trait (white flowers) had not been seen at all in the F1 generation, it had been retained, and could be recovered in the F2 generation. These results clearly supported the particulate theory.
To obtain his results, Mendel studied the transmission of seven distinct phenotypes among some 28,000 pea plants, and synthesized them into a mathematical model of genetic inheritance. In doing so, he did what had never been done before; he quantified his results. From an analysis of his data, he was able to infer several key principles. He argued that there must exist determinants that specify particular phenotypes, a feature we now recognize as genes. He also argued that these determinants are located on particles, one of which is donated by the father, and one by the mother. These particles, now known to be chromosomes, produce a progeny plant that has one determinant for flower color donated by the mother, and one determinant for flower color donated by the father. The phenotype of the progeny plant will depend upon the particular combination of determinants it receives from its parents. Mendel deduced that the determinant for the production of purple flowers (represented as "P") is dominant over the determinant to produce white flowers (represented as "p"). Conversely, the white flower determinant is recessive in the presence of the purple-flower determinant. Two copies of the purple-determinant (P/P) in a plant, one maternal and one paternal, results in purple flowers. One purple and one white flower determinant (P/p) still produces purple flowers. Only if a plant receives two white flower determinants (p/p) will it possess white flowers.
Mendel's results were not widely known at the time. Some thirty-five years later, his work was "rediscovered" by geneticists who had repeated his results in other organisms. The implications of Mendel's work were revolutionary. For the first time, it was possible to observe the patterns of inherited phenotypes of a plant, animal, insect, or bacterium, and deduce, with mathematical precision, the expected genotypes of these organisms. It is a tribute to the work of Mendel and others of his time that their results were obtained despite not knowing that genes were encoded by DNA or how genes act to produce the observed phenotype.
Single Gene Effects
Part of Mendel's success was due to his implicit recognition that there are two primary types of variation: discontinous and continuous. In discontinuous variation, a particular phenotype can be found in a population in at least two distinct forms. For example, Mendel's peas possessed purple or white flowers, and not both. On the other hand, in continuous variation, a range of similar phenotypes can be observed in the population. An example of this among humans might be the observation that noses come in all shapes and sizes. In most instances, genetics has focused predominantly upon discontinuous variants, as the associated phenotypes can be clearly recognized and categorized. As it turns out, many of the phenotypes that fall into this group can be associated with alterations in the function of a single gene. In our purple versus white flower example, the gene that is normally responsible for giving the plant its purple color has been mutated, such that it no longer functions. In the absence of this gene, white, or uncolored, flowers are produced. The different forms of this same gene (P, indicating normal or wild-type function, and p, indicating altered or mutant function) are called alleles. If an allele is widely represented in the population, as is the case among white or purple flowers in pea plants, they are termed polymorphisms.
Polymorphisms can be identified in other organisms as well. However, in humans, there are also additional issues of ethnicity and race. A common polymorphism among Asians, for example, is a particular allele of the alcohol dehydrogenase 2 (Adh2) gene. This allele negatively affects the enzyme's ability to metabolize alcohol, and is possessed by more than 90 percent of the Japanese population. In the European population, on the other hand, less than 10 percent have this allele. Similarly, lactose intolerance is due to allelic variation in the lactase gene. An allele that leads to low activity of lactase following early childhood is common in Africans and Asians (>80 percent), and rarer in Caucasians (17–50 percent). These relatively common polymorphisms are just a few of the many thousands of alleles known to exist in humans.
Why these polymorphisms exist is not clear, although it can be hypothesized that they either do no harm to individuals who harbor these particular alleles, or, if they are in fact somewhat harmful, are nonetheless still of some benefit. This can be described as the fitness of the allele. For example, as many as 10–20 percent of the European population bears a polymorphism in the gene encoding methylenetetrahydrofolate reductase (MTHFR). These individuals have a greater risk of neural tube defects, such as spina bifida, due to the fact that this allele affects folate metabolism. Why then, is such a polymorphism maintained in such a high percentage of the population? The answer may lie in the observation that individuals with this polymorphism have an increased efficiency of blood clotting. As mortality resulting from bleeding after childbirth was a common occurrence, this would be beneficial to individuals bearing this polymorphism. While it is often dangerous to speculate why a polymorphism exists, if this reduction in risk is substantiated, it would obviously be of benefit both to the individual and the population as a whole.
While we have centered this discussion around polymorphisms, on occasion, an allele will arise that affects only a small percentage of the population. Although these rare variants are uncommon (<1 percent of the population), they make up a large proportion of the patients that are hospitalized for medically related conditions. One such example would be phenylketonuria, which occurs in one out of every 10,000 births. This medical condition is due to a mutation in the phenylalanine hydroxylase gene, and leads to a failure to metabolize phenylalanine containing compounds, such as aspartame. If unrecognized, infants with PKU invariably develop mental retardation. This can be avoided by monitoring dietary intake to eliminate phenylalanine-containing compounds. How is PKU inherited from one generation to another? The fields of medical genetics and genetic counseling encompass the analysis of family histories, so as to better treat individuals who are at risk from these illnesses. If we examine the family history of a typical patient that has PKU, we might observe the following:
In this case, neither parent in the P0 generation suffers from the disease, but some of their children do. Applying principles learned from Mendel's work, we can infer the genotype of the family members from this phenotypic analysis:
From the study of this family history, it is clear that PKU is inherited in a recessive manner. Adults who are heterozygous for mutations in the phenylalanine hydroxylase gene (K/k; possessing one wild-type or normal allele and one mutant allele) do not have PKU. Only those with two mutant copies (k/k) display the condition. Thus, Mendel's laws apply equally well to humans as they do to peas. Interestingly, however, while the phenotype of PKU patients indicates a recessive inheritance of this condition, an analysis of the genotype of these patients and the population in general reveals the existence of more than 400 alleles of the phenylalanine hydroxylase gene. This astounding degree of allelic heterogeneity indicates that most PKU patients indeed possess two mutant alleles of the hydroxylase gene, but that these two alleles are likely to be completely different. The phenotypic effect is the same; elimination or severe alteration of the normal function of the gene leads to PKU. The molecular basis of this defect, however, is dependent upon the specific alleles that are involved. It is plain to see that the field of molecular genetics, which examines the actual genes responsible for these defects, is an important complement to more traditional genetic phenotypic observations.
While the examples we have looked at so far have comprised diseases or phenotypic traits that are inherited in a recessive fashion, many diseases are inherited in a dominant manner. In these instances, a single copy of the mutant allele is sufficient to confer, at least partially, a medically associated condition. An example of this might be familial hypercholesterolemia, which is associated with an inability to properly metabolize cholesterol. A family history of patients with this affliction might appear thus:
Compare the rate of occurrence of this condition with that of PKU. Only a single copy of the mutant allele is required to produce at least some phenotype in cases of familial cholesterolemia. In many of these dominantly inherited diseases, individuals that possess two mutant alleles are much more strongly affected than individuals with one mutant and one wild-type allele. In familial hypercholesterolemia, homozygous patients (those with two mutant alleles; H/H) rarely live past the age of 30. These individuals are rare, however, occurring in perhaps one in one million. Heterozygous individuals (those with one mutant and one wild-type allele; H/h), on the other hand, are extremely common, and are present in perhaps one in 500. These individuals have a higher propensity for premature heart disease due to the buildup of atherosclerotic plaques, but without the severity of phenotype exhibited by homozygous individuals.
These examples illustrate just a few of the more than 1400 single-gene disorders that have been identified. It has been estimated that in any one individual, perhaps 20 percent of all genetic loci are heterozygous. This suggests that a striking degree of individuality exists at the genetic level. This allelic variation may explain, for example, the differential response of individuals to environmental, dietary, or pharmacological effects.
Multiple Gene Interactions
So far, we have discussed examples of phenotypes that can be traced to alterations of a single gene. While great strides have been made in identifying genes that are associated with a particular phenotype, it is clear that we are far from understanding how genes interact with one another as a whole. For example, many genetic disorders are thought to result from the interplay of multiple genes with epigenetic, or environmental, influences, such as diet. One means of trying to understand these multifactorial disorders and how genes and the environment interact is to examine at a molecular level how genes function. While Mendel derived his results from observing the phenotype of his plants, a molecular geneticist might ask, what is the actual gene that is responsible for production of purple pigment? What is its sequence? How does it function in the plant cell to produce color? With what other genes does it interact?
DNA has often been called the "blueprint of life," and indeed, DNA is the thread that ties almost all life on earth together. Rules that govern the replication of DNA and its transmission to daughter cells (e.g., during cell division) are the same in nearly all organisms. But if DNA is DNA whether or not it is found within a fly or a human, how is it possible to obtain such diverse organisms? The answer, of course, is that the genes that exist within DNA are different from flies to humans. One might suspect that these two diverse organisms would possess radically different sets of genes, separated as they are by over 600 million years of evolution. With the advent of the Human Genome Project, it has become possible to directly test this hypothesis. Once the entire sequence of human DNA was known, it was compared to the sequence of Drosophila melanogaster, a fruitfly that has been used for over one hundred years as a genetic model. This comparison revealed an astonishing 40 percent of all genes in the human have similar counterparts in the fruit fly. While this figure is still tentative, and gene number is hardly an adequate means of comparing differences among species, it underscores yet again that genetic principles learned in model organisms, such as the fruit fly, can have important theoretical and practical applications in understanding human genetics.
If variation between species is accomplished, at least in part, by genes that are unique to flies or humans, how does variation occur within a species? All cells in the human body, with the exception of those involved in the production of sperm or ovum, contain identical DNA sequences, and therefore identical sets of genes. How is it then, that a skin cell will develop differently from a hair cell, if both contain the same DNA? The answer is that each cell may contain the same genes, but not all the genes will be expressed in each cell. Current estimates suggest that there are approximately 50,000 genes in the human genome. Any given cell type, however, is thought to express some 15,000 of these genes. Thus, a hair cell will express 15,000 genes, but these genes will be somewhat different from the 15,000 that are expressed by a skin cell. It is this differential gene expression that leads to the differences in observed phenotype between the two cell types. In a similar vein, two noses located on the faces of two different individuals may well be specified by the same 15,000 genes, but slight differences in their expression from one individual to the next may well explain the somewhat petite nose on one and the rather large proboscis on the other. The growing field of genomics aims to study, at a global level, the interactions of all of the genes that contribute toward a particular phenotype.
If it does indeed require 15,000 genes to produce any given cell in the body, then mutant alleles that arise in any one of these genes may, or may not, strongly affect the development of that cell. Alleles of certain genes may alter the color of the cell, or perhaps its ability to metabolize phenylalanine-containing products. Or it is possible that an alteration in just one gene among 15,000 may have no discernable effect at all. How these thousands of genes interact with one another to produce a given trait is perhaps the biggest challenge that faces the molecular geneticist studying genomics today. Moreover, these genetic interactions are often complicated by epigenetic influences as well. Nutrition, in particular, has very strong effects on gene expression. Many multifactorial diseases, such as diabetes, are thought to be associated with both genetic and environmental risk factors. A given family history may, to the medical geneticist, indicate a predisposition towards diabetes, but other factors, such as diet and exercise, are also thought to influence the development of this disease.
One particularly fascinating example of the link between nutrition and genetics is the effect of diet upon aging. Unusual longevity in humans has often been attributed by these self-same individuals as directly associated with the manner in which they have lived their life. Whether it is a glass of wine each day, eliminating red meat, or ingesting large quantities of vitamin C, these individuals claim to have identified the reason behind their advanced years. How much can truly be attributed to these epigenetic influences, and how much is based upon the individual's particular genetic makeup? Research in model organisms such as the fruit fly has identified a handful of genes that seem to strongly affect the lifespan of the fly. Mutations in the methuselah gene, for example, allows flies to survive more than 35 percent longer than their normal lifespan. This astonishing result suggests that aging may actually be strongly influenced by a limited number of genes, many of which are involved in metabolism. On the other hand, it has long been known that reducing the calorie intake of rodents by 40 percent can also markedly increase their lifespan. The new field of genomics has begun trying to identify the molecular basis for this increase in longevity, by comparing how many genes are differentially expressed between calorie-restricted rodents and their non-restricted counterparts. It was found that hundreds of genes had been affected, including a large number known to be involved in metabolic processes. Thus, the effects of nutrition on aging can be profound. How much of this is due to our genes? How much can attributed to single genes? How much is due to our caloric intake? The answer to this "age-old" question remains to be determined.
A similarly tantalizing example demonstrating the link between nutrition and genetics lies in the area of control of bodyweight. Mice that are homozygous mutant for a particular allele of the obese gene (ob/ob) are grossly overweight. The excitement that surrounded this result centered around the possibility that weight gain might be strongly influenced by individual genes, and that no amount of dietary control or exercise can alleviate its effects. This, of course, has been shown to be a gross oversimplification, and it is clear that many genes are involved in the regulation of body weight. Nevertheless, it is apparent that the field of genetics is gradually beginning to unravel some of the major problems in nutrition and biology today.
The practice of genetics is as old as the human race, and yet as a science, it is still in its infancy. The study of genetics stretches across all of biology, and has grown to include many sub-specialties within the field. Cytogenetics, for example, is the study of chromosomal defects, such as trisomy 21. Molecular genetics is the analysis of individual genes, such as Adh2, and their function within the cell. Population genetics studies the frequency with which polymorphisms of Adh2 occur within large subsets of individual organisms. Medical genetics searches to identify patterns of inheritance of diseases within patients, and the effect of epigenetic influences such as diet and exercise. And finally, genomics tries to understand how genes behave as a whole to specify particular cell types or phenotypes. Together, these diverse but inter-related fields aim to understand how variation is established and maintained within biology.
See also Agriculture since the Industrial Revolution; Crop Improvement; Gene Expression, Nutrient Regulation of; Genetic Engineering .
Brown, P. O., D. Botstein. "Exploring the New World of the Genome with DNA Microarrays." Nature Genetics 21 (1 Suppl) (1999): 33–37.
Griffiths, Anthony J. F., J. H. Miller, David T. Suzuki, Richard C.Lewontin, and William M. Gelbart. An Introduction to Genetic Analysis. 7th ed. New York: Freeman, 2000.
Jorde, Lynn B., John C. Carey, Michael J. Bamshad, and Raymond L. White. Medical Genetics. 2d. ed. St. Louis: Mosby, 1999.
Lee, C. K., Weindruch Klopp, T. A. Prolla. "Gene Expression Profile of Aging and its Retardation by Caloric Restriction." Science 285 (1999): 1390–1393.
David Ming Lin
Genetics is the branch of biology concerned with the science of heredity. The term heredity refers to the way in which specific characteristics are transmitted from one generation to the next. For example, we know that a tall mother and a tall father tend to have children that are tall. Geneticists (scientists who study genetics) are interested in finding out two things about this observation. First, what is there in the cells of a person's body that directs the body to become tall rather than short. Second, how are the directions for "tallness" transmitted from parent to offspring, from one generation to the next?
The history of genetics
Humans have known about hereditary characteristics for thousands of years. That knowledge has been used for the improvement of domestic plants and animals. Until the late nineteenth century, however, that knowledge had been gained by trial-and-error experiments. The modern science of genetics began with the pioneering work of the Austrian monk and botanist Gregor Mendel (1822–1884).
Words to Know
DNA (deoxyribonucleic acid): Molecules that make up chromosomes and on which genes are located.
Dominant gene: The state or genetic trait that will always express itself when present as part of a pair of genes in a chromosome.
Gene: A section of a DNA molecule that carries instructions for the formation, functioning, and transmission of specific traits from one generation to another.
Heredity: The transmission of characteristics from parents to offspring.
Nucleotide: A group of atoms present in a DNA molecule.
Proteins: Large molecules that are essential to the structure and functioning of all living cells.
Recessive gene: The state or genetic trait that can express itself only when two genes, one from both parents, are present and act as a kind of code for creating the trait, but will not express itself when paired with a dominant gene.
Triad: Also known as codon; group of three nucleotides that carries a specific message for a cell.
Mendel studied the genetic characteristics of pea plants. He was interested in finding out how certain traits, such as flower color and plant height, were passed on from generation to generation. During his lifetime, he studied dozens of generations of plants of all sizes, shapes, and colors. As a result of his research, Mendel was able to state a few basic laws describing the way genetic traits are inherited. He also came to the conclusion that there must be a specific biological unit responsible for the transmission of genetic traits. He called that unit a factor. Mendel's "factors" were later given the name of genes.
Without question, Mendel was the father of the modern science of genetics. One of the great ironies of history, however, was that his discoveries were lost for more than three decades. Then, in the early 1900s, Mendel's research was rediscovered almost simultaneously by three different biologists, the Dutch botanist Hugo de Vries (1848–1935), the German botanist Karl F. J. Correns (1864–1933), and the Austrian botanist Erich Tschermak von Seysenegg (1871–1962).
Although interest in genetics grew rapidly after 1900, a fundamental problem remained. Geneticists based all of their laws, theories, and experiments on the concept of the gene. But no one had any idea as to what was a gene. It seemed clear that the gene was probably some kind of chemical compound, or some combination of compounds. But no one had been able to determine exactly what kind of compound or compounds it was.
The answer to that question came in 1953. The American biologist James Watson (1928– ) and the English chemist Francis Crick (1916– ) collaborated to discover that a gene was a section of a very large and complex molecule found in the nuclei of all cells, the deoxyribonucleic acid (DNA) molecule.
The chemistry of genes
Imagine a very long chain of beads strung together to form a strand containing hundreds of thousands of beads. The strand contains beads of only four colors: red, yellow, blue, and green. That strand of beads can be compared to half of a DNA molecule. The other half of the molecule is a second strand almost identical to the first strand.
Watson and Crick showed that the sequence in which various colors of beads occur is significant. A DNA molecule in which the beads are arranged in the sequence blue-yellow-yellow-red-red-blue-blue-blue-, and so on, has meaning for a cell. The sequence tells the "chemical machinery" of the cell to make a certain kind of protein, such as the protein responsible for red hair or blue eyes. Another sequence of colors, for example, red-red-yellow-green-blue-green-red-, and so on, might be the "code" for making blonde hair or green eyes.
The components of a DNA molecule are not, of course, colored beads. They are certain groups of atoms known as nucleotides. Each nucleotide in a DNA molecule is comparable to one of the colored beads in the analogy above. Just as there are only four colors of beads in the above analogy, so there are only four different nucleotides in DNA molecules. Those nucleotides might be represented by the symbols A, C, G, and T (corresponding to bead colors of red, blue, green, and yellow). A DNA molecule, then, is a very long chain of nucleotides with a structure something like the following:
The dots at the end of the chain indicate that the chain actually goes on much, much longer.
Watson and Crick said that each set of three nucleotides—they called them triads or codons—carried a specific message that cells could understand. Those messages told a cell to "make red hair," or "make blue eyes," or "help a person to grow tall," or "give a person musical talent," or any one of thousands of other traits that each human possesses.
This discovery answered the first question that geneticists had about heredity: how cells know which traits they are "supposed" to make and what functions they are "supposed" to carry out. The same discovery also answered the second question puzzling geneticists: how do these traits get passed down from generation to generation?
The answer to that question is that DNA molecules have the ability to make copies of themselves. When a cell divides (reproduces), so do the DNA molecules it contains. In most cases, two exactly identical molecules are produced from a single parent molecule.
When an egg cell (female reproductive cell) and a sperm cell (male reproductive cell) unite during fertilization, each cell provides DNA to the fertilized egg. The DNA from both parents combines to form DNA for the offspring. Whatever nucleotide sequences the mother and father had in their own cells, they pass on to their child.
Dominant and recessive traits
One fundamental question remains in the above example: suppose that a child is born to a father with red hair and a mother with blonde hair. What color hair will the child have?
Mendel worked with this question long before Watson and Crick discovered the nature of DNA. He found that for any one genetic trait, there were always two possible conditions. A flower might be red or white; a plant might be tall or short; a pea pod might be smooth or wrinkled; and so on. Mendel also discovered that one of these two conditions was more likely to "win out" over the other. He called the "winner" the dominant trait and the loser the recessive trait.
If a pea plant inherits a "tall" gene for height from both parent plants, the offspring is most like to be tall. If the pea plants inherits a "short" gene for height from both parent plants, the offspring is most likely to be short. But if the pea plant inherits a "tall" gene from one parent and a "short" gene from the second parent, the offspring is most likely to be tall.
An important part of Mendel's work was finding out what the mathematical chances of various kinds of combinations might be. For example, he showed how to calculate the probabilities that would result when a "tall" parent pea plant was crossed with a "short" parent pea plant in the first, second, and succeeding generations.
The future of genetics
One can apply the principles of genetics in a great many situations without knowing anything about the structure of DNA molecules. However, the Watson-Crick discovery made possible a revolutionary change in the basic nature of genetics. As long as scientists had no idea as to what a gene was, there was not much they could do to make changes in the genes of a plant, animal, or human. But Watson and Crick showed that genes are nothing other than chemical compounds. If someone can make changes in chemical compounds in a laboratory, that person can also make changes in a DNA molecule. The problems faced are a good deal more difficult since DNA molecules are far more complex than most molecules that chemists work with. But the basic principles involved are the same.
Scientists are exploring a variety of ways in which genes can be modified to produce cells that can do things they could not do before. For example, it is possible to create the gene for the hormone (chemical messenger) known as insulin in a chemical laboratory. The work is fairly difficult, but by no means impossible. It simply requires that the correct atoms be assembled in the correct sequence. That artificial gene can then be inserted into the DNA of other organisms, such as bacteria. When the artificial gene becomes part of the bacterial DNA, it begins to function just like all the other genes in the bacteria's DNA. The bacteria begins to function as an "insulin factory," making a vitally important compound that it could never make before.
One of the most exciting recent developments in genetics is the initiation of the Human Genome Project, which officially began on October 1, 1990. This project is designed to provide a complete genetic road map outlining the location and function of the approximately 50,000 genes in human deoxyribonucleic acid (DNA) and to determine the sequences of the 3,000,000,000 base pairs that make up human DNA. As a result, genetic researchers will have easy access to specific genes to study how the human body works and to develop therapies for diseases. Gene maps for other species of animals also are being developed.
There appears to be virtually no technical limit to the things that scientists can do with genes. But with the promise of genetic research, many ethical and philosophical questions arise. One question is, of course, whether there are social or ethical limits to the kinds of changes scientists ought to be allowed to make in the genes of plants, animals, and humans. With research focusing on the ability to manipulate genes, there is the fear that the results will not always be beneficial. For the most part, the benefits for medicine and agriculture seem to far outweigh the possible abuses, and genetic research continues.
[See also Chromosome; Human Genome Project; Nucleic acid ]
GENETICS, the science of heredity, includes the interrelated fields of cytology, biochemistry, evolutionary theory, and molecular biology. Today the impact of genetic research is far-reaching, affecting medical diagnosis and therapeutics, agriculture and industry, criminal prosecution, and privacy, as well as ideas regarding individuality, ethics, and responsibility. Studied since antiquity, heredity remained a puzzle until the late twentieth century even though many of its essential physical components—such as chromosomes and "nuclein" (later identified as deoxyribonucleic acid (DNA)—were known by the late nineteenth century. Indeed, genetics did not become a "science" in a contemporary empirical sense until the rediscovery of Gregor Mendel's laws in 1900. Mendel, an Austrian monk who experimented with patterns of inheritance in studies of peas and flowers, determined laws of heredity regarding the integration and assortment of inherited traits. These original principles underwent considerable refinement and expansion throughout the twentieth century as scientists uncovered the physical and chemical mechanisms of heredity. This recent history of genetics can be divided into three general periods: classical genetics, molecular genetics, and applied or modern genetics, each of which benefited greatly from American researchers and institutions.
Classical and Molecular Genetics
The rediscovery of Mendel's laws led to the flowering of classical genetics in the early twentieth century. Population studies, breeding experiments, and radiation were among the early tools in genetic research as scientists looked to uncover the patterns and basic unit of heredity as well as the causes of variation. In 1902, a mere two years after the rediscovery of Mendel's laws, the American biologist Walter S. Sutton observed similarities between Mendel's genetic "units" and chromosomes. Additional research by his Columbia University colleague Edmund Beecher Wilson confirmed the link and identified the "X" sex chromosome in butterflies, while another American, the cytologist Nettie Stevens, independently identified the "Y" chromosome in beetles. The existence of sexlinked genetic traits, such as white eyes in fruit flies (Drosophila melanogaster), was shown by the American biologist Thomas Hunt Morgan in 1910 in studies capable of locating a specific gene on a specific chromosome. Using light-microscope observations, Morgan and his students Alfred Henry Sturtevant, Hermann Joseph Muller, and Calvin Blackman Bridges studied the phenomenon of crossing-over, the process by which chromosomes exchange genes, and as a result were able to construct chromosome maps. Their research proceeded quickly; in 1915, the "Drosophila" group at Columbia University published The Mechanism of Mendelian Heredity—a seminal work that demonstrated the linear arrangement of genes in the chromosome and helped explain abnormal genetic ratios and variation. However, explanations for genetic variation remained unsatisfactory until the pioneering work of Hermann Muller at the University of Texas. Muller experimented with radiation and high temperatures to measure rates of mutation, eventually determining that genes, while generally stable, can be externally induced to mutate. (This discovery also opened the possibility of genetic engineering.) His Artificial Transmutation of the Gene, published in 1927, also hinted at the gene's ability to control metabolism and morphology, leading biochemists and other scientists to investigate the physical composition of the gene and the chemical basis of heredity.
Beginning in the 1940s, techniques such as bacterial vectors and X-ray diffraction analysis led to the development of both biochemical genetics and molecular genetics. In 1941, the Stanford biologist George Wells Beadle and biochemist Edward Lawrie Tatum proposed the one gene–one enzyme theory after experimenting on the nutritional requirements of mutated bread mold, ushering in the field of biochemical genetics by providing an introductory blueprint for the chemical synthesis of enzymes. A few years later, in 1944, the American geneticists Oswald Avery, Colin MacLeod, and Maclyn McCarty transformed bacteria through the introduction of foreign DNA, thereby determining that DNA was the primary heredity material. This indicated that DNA, rather than the previously suspected class of proteins, was the actual carrier of genetic information. Further proof came in 1952 when the American geneticists Alfred D. Hershey and Martha Chase, working at the Cold Spring Harbor Biological Station in New York, demonstrated that viral DNA was responsible for replication within infected bacteria. Using a bacteriophage (a bacterial virus) as a vector, the scientists showed that it was the virus's DNA, not a protein, that infected the host bacteria. However, while DNA was clearly the molecule of heredity, questions on the structure and mechanisms of DNA remained that could only be solved by molecular biology.
By 1950, geneticists had adopted the method of X-ray diffraction analysis pioneered by the American chemist Linus Pauling at the California Institute of Technology to determine the three-dimensional structure of the DNA molecule. Pauling proposed both single-and triple-helix models, but in 1953 the American biochemist James Watson and British biophysicist Francis Crick correctly determined that the DNA molecule was a double helix. The two men proposed that DNA was transcribed into RNA, then translated or expressed as a protein, a method of genetic replication later proven by the American molecular biologists Matthew Stanley Meselson and Franklin William Stahl and now known as the "central dogma" of molecular genetics. In 1961, Crick and Sidney Brenner determined that codons, groups of three nucleotides (adenine, cytosine, guanine, uracil and thymine), were responsible for the synthesis of proteins, while the National Institutes of Health researchers Marshall W. Nirenberg and Johann H. Matthaei showed in 1965 that certain codon combinations also lead to the production of amino acids. A final piece of the genetic puzzle—the means by which genes are activated or deactivated—was resolved by the operon model of genetic regulation. Proposed by the Frenchman Jacques Monod, the operon model requires that regulatory nucleotides, which account for a substantial portion of the DNA molecule, repress the function of other genes by disrupting RNA transcription under certain conditions.
Modern Applied Genetics
The study and sophistication of genetics increased rapidly in the last quarter of the twentieth century, as scientists, aided by advances in technology and industry and government funding, concentrated on both pure and applied genetics. Recombinant DNA engineering and prenatal genetic screening for some inherited diseases became possible in the early 1970s, leading to public concern over potential misuse and eventual governmental regulation. At the same time, the central dogma expanded to include the phenomenon of reverse transcription after American virologist David Baltimore demonstrated that retroviruses were capable of reproducing themselves by copying their own RNA. Perhaps the greatest advancement in pure genetic research came in the form of the Human Genome Project. Launched in 1988 by the U. S. Department of Energy and the National Institutes of Health, the Human Genome Project succeeded in sequencing a human genome in 2000 and represents the new state of "big" biology—an international partnership of government, academic, and industrial research institutions. Although researchers expect that the project will deliver remarkable medical and biological applications, some outside observers worry about the potential for genetic discrimination, genetic racial typing (see Racial Science), and the revitalization of Eugenics, demonstrating both the promise and the danger of contemporary genetics.
Today genetics permeates both the biological sciences and American culture, surfacing in research laboratories, congressional hearings, and courtrooms as well as popular movies and books. Genetics has unified the biological sciences and led to the modern synthesis of evolutionary theory and biology by demonstrating that organisms share the same basic genetic materials and processes. DNA fingerprinting plays a vital role in criminal investigations and the establishment of paternity, while genetic screening and therapy provide hope for those suffering from inherited diseases like sickle-cell anemia, cystic fibrosis, or Huntington's disease. Entering the twenty-first century, transgenic crops may provide the best window into the future impact of genetics, as the rise of a transgenic agricultural industry, which produces crops with an increased pesticide resistance and shelf life, has also led to a counter industry based on organic, or non-genetically enhanced, crops.
Caulfield, Timothy A., and Bryn Williams-Jones, eds. The Commercialization of Genetic Research: Ethical, Legal, and Policy Issues. New York: Kluwer, 1999.
Kohler, Robert E. Lords of the Fly. Chicago: University of Chicago Press, 1994.
Olby, Robert. The Path to the Double Helix. Seattle: University of Washington Press, 1974. Reprint, New York: Dover, 1994.
Ridley, Matt. Genome: The Autobiography of a Species in 23 Chapters. New York: Harper Collins, 1999.
Sarkar, Sahotra. Genetics and Reductionism. Cambridge, U. K., and New York: Cambridge University Press, 1998.
Sturtevant, A. H. A History of Genetics. New York: Cold Spring Harbor Laboratory Press, 2001.
genetics, scientific study of the mechanism of heredity. While Gregor Mendel first presented his findings on the statistical laws governing the transmission of certain traits from generation to generation in 1856, it was not until the discovery and detailed study of the chromosome and the gene in the 20th cent. that scientists found the physical basis of hereditary characteristics. A brief summary of the basic laws of heredity and the terms used follows.
Basic Laws and Terminology
The gene is defined as the unit of inheritance. A gene is actually a sequence of DNA (see nucleic acid) contained by and arranged linearly along a chromosome. Each gene transmits chemical information that is expressed as a trait, e.g., tall or dwarf size in the garden pea plant. Each species has a genome, or characteristic set of genes, that contains the total genetic information for an individual organism. In many familiar organisms two genes for each trait are present in each individual, and these paired genes, both governing the same trait, are called alleles. The two allelic genes in any one individual may be alike (homozygous) or different (heterozygous). The chromosomes of animals and plants that reproduce sexually usually exist in pairs; the members of a chromosome pair are termed homologous (see reproduction). In humans there are 46 chromosomes, or 23 homologous pairs. Pairs of genes are borne on homologous chromosomes.
In the process of meiosis, by which ova and sperm are produced, the chromosomes are so divided that each mature sex cell contains half the original number of chromosomes, or one chromosome of each pair, and therefore one gene of each pair. Thus, when the ovum and the sperm fuse on fertilization, the fertilized egg (zygote) receives one allele from each parent. With many pairs of alleles that have contrasting effects (e.g., certain alleles produce different eye color), one is dominant and the other recessive: an individual heterozygous (carrying contrasting alleles) for a given characteristic invariably displays one aspect of that characteristic and not its alternative, although the gene for the aspect that does not appear (i.e., that is recessive) is present. This individual is called a hybrid.
In Mendelian law (see Mendel) the offspring—or first filial (called F1) generation—of parents each homozygous for different alleles of a given gene are all hybrids heterozygous for the characteristic governed by that gene and are said to be of the same phenotype, i.e., they are all similar in appearance to the homozygous dominant parent because the recessive characteristic is masked, although their gene composition, or genotype, is different from either parent. A cross of members of the F1 generation produces a second filial (F2) generation of which approximately three fourths show the dominant characteristic and one fourth the recessive. Note however, that great numbers of characteristics are inherited simultaneously and the patterns of transmission of genes are such that offspring strongly resembling one parent in certain traits can resemble the other parent in other traits.
It has also become clear that an individual organism's heredity and environment interact in the manifestation of many traits: a pea plant with a genetic tendency toward tallness will not achieve its full size if deprived of adequate water and minerals for growth. However, true alterations in gene and chromosome structure are the product of mutation and are not produced by environmental conditions, as was postulated by the theory of acquired characteristics. The discovery by H. J. Muller in 1927 of methods for artificially inducing mutations by means of ionizing radiations and other mutagens opened the way for much new genetics research.
Modifications of Mendel's Principles
Modification of Mendel's principles developed as knowledge of the chromosomes increased; many discoveries have helped to account for apparent deviations from Mendelian ratios. For example, Mendel's studies emphasized genes that behave independently from one another during transmission to offspring. But we now know that genes are transmitted as constituents of chromosomes, each of which carries many different genes, which sheds light on the tendency of certain characteristics to appear in combination with one another (linkage). It also has been found that some characteristics are sex-linked, i.e., are transmitted by genes carried by the sex chromosomes (see sex); and that a non-sex-linked gene inherited from the father may differ in its expression from the same gene inherited from the mother, a phenomenon called "imprinting." Other research has shown that there may be multiple alleles (more than two alternative genes) for a given characteristic: the human blood groups are determined by a combination of several possible alleles. It is apparent that homologous portions of paired chromosomes may be interchanged during meiosis (crossing over) and that the interaction of many genes is responsible for determining many of the traits of individuals. Since the discovery (1953) of the structure of DNA, work on nucleic acids has begun to explain how genes determine life processes by directing the synthesis of proteins. It has also explained mutations as alterations in gene or chromosome structure. It has been found, for example, that mutations in the form of repeated sequences of otherwise normal chemical bases, can grow in length with succeeding generations, in some cases causing diseases (e.g., myotonic muscular dystrophy) that increase in severity each time they are inherited.
Most of the knowledge of chromosome structure and the behavior of genes has come from studies of the vinegar, or fruit, fly (Drosophila melanogaster), which reproduces so rapidly that many generations can be studied over a short time. The work of T. H. Morgan and his associates on Drosophila was the basis of much of the early progress of genetics in the United States. Certain other small laboratory animals, plants, and microorganisms such as the E. coli bacteria are now used, also largely because of their ability to reproduce rapidly. For obvious reasons human beings are poor subjects for experimental genetic studies; however, much that aids understanding heredity in humans has been learned from the "lower" forms of life. Also, by tracing the appearance of certain abnormal characteristics (e.g., hemophilia, color blindness, and certain mental disorders and anatomical defects) and blood groups through a number of generations the hereditary pattern of these conditions has been established. The increasing ability of scientists to decode genetic information (see Human Genome Project) has led to a considerable expansion of knowledge about the nature and role of genes in humans and other organisms. Application of this knowledge has played an important role in the fields of gene therapy, genetic engineering, and evolutionary studies, and has resulted in a better understanding of the genetic components of disease, physical characteristics, mental illness, and even personality.
The study of mutations, together with the analyses of population genetics, has been used to explain the mechanism of evolution. The elementary process of evolution is considered to be the changes in the frequency of occurrence of alleles in a population. Mutation, which causes the appearance of new alleles or changes the relative frequency of already existing alleles, is one important mechanism by which evolution occurs. Natural selection (see selection), by affecting reproductive success, influences the frequencies of alleles and other genetic variants in successive generations. For example, if the presence of a particular allele makes a homozygous individual unable to mate, the allele may be eliminated from the population.
Genetic drift —the random fluctuation in the frequency of an allele, resulting mainly from the vagaries of chance mating—is also an evolutionary mechanism. Although in large populations drift varies only a little above and below a statistical mean, in small breeding populations an entire generation might, by chance alone, be born with the same genotype with respect to a particular allelic pair of genes, thus leading to either the elimination or dominance of a particular gene. Because fluctuations in the proportions of alleles are more significant in the gene pools of small, isolated breeding populations, genetic drift is a mechanism of species diversity and evolution in such groups.
See T. Beebe and J. Burke, Gene Structure and Transcription (1988); R. McKie, The Genetic Jigsaw (1988); G. L. Stine, The New Human Genetics (1988); G. W. Burns and P. J. Bottino, The Science of Genetics (1989); C. Wills, The Wisdom of the Genes (1989); G. Edlin, Human Genetics (1990); B. Lewin, Genes IV (1990).