Sex Determination

Sex determination is the process by which organisms develop as males or females. Some organisms reproduce only by asexual methods, and thus they may possess no system for sexual differentiation. For most species of plants and animals, however, sexual development is a basic element of the normal life cycle. In humans, sex is a fundamental characteristic that influences the development of many of the features of the body. This includes some obvious traits such as genital and breast development, but it also includes structures in the brain and other internal organs, the shape and mineral composition of bones, and a wide array of features observable at the cellular level.

The many clues, overt or subtle, that can be collected from careful examination of the bodies, organs, tissues, and even cells of the deceased remove much of the mystery of the sex of a victim whose remains are recovered from the scene of a crime, or the site of a fire, explosion or other disaster.

In humans, where there are two distinct sex chromosomes, the X and the Y chromosomes, it is the presence of the Y chromosome that specifies male development. More specifically, there is a gene on the Y chromosome called the sex-determining region of the Y chromosome (SRY) that causes male development. In fact, female development seems to be the default pathway, and in the absence of SRY, the urogenital tract develops as a female. The elementary structures for both male and female development are present in the early embryo, however, development of the female ductal system, called the Mullerian system, is inhibited by a substance produced by the early male embryo. Likewise, in females, the primordial male ductal system, called the Wolffian duct, degenerates as the Mullerian ductal system advances. The Mullerian ducts give rise to the fallopian tubes, uterus, and upper portion of the vagina. The Wolffian ducts give rise to the spermatic ducts and seminal vesicles which carry sperm from the mature testes during ejaculation. Although SRY, the primary sex-determining gene, is found on the Y chromosome, many of the genes responsible for development of both male and female reproductive structures and other sexual characteristics are found on the autosomes.

One of the earliest events in male development is the production of testis-determining factor within the sex cord cells. The sex cords begin to differentiate into Sertoli cells when SRY is present. The Sertoli cells secrete male-specific factors such as Mullerian inhibitory substance (MIS), which causes the female ductal system to degenerate. MIS also promotes the development of another male-specific cell population called Leydig cells, which produce testosterone. For female embryos, because of the absence of SRY, the sex cords develop along a different pathway to develop structures associated with the ovaries. As the embryo develops, hormones produced by the testes in males and the ovaries in females create a biochemical environment in which the more subtle elements of sexual development occur.

Sexual development is not always so straightforward in humans. Although people are usually considered either male or female, various disruptions can occur during sexual development and differentiation that give rise to atypical or mixed sexual development. These include sex chromosome abnormalities, where there are extra or missing copies of the sex chromosomes. This would include Turner syndrome, where females receive only a single X chromosome; Klinefelter syndrome, wherein males receive not only an X and Y chromosome but also an extra copy of the X chromosome; and a wide variety of other more rare numerical sex chromosome abnormalities where extra copies of the X and/or Y chromosomes are present. In addition, the SRY gene that is normally transmitted on the Y chromosome can become translocated to an X chromosome or an autosome, resulting in a reversal of sex. Also, when multiple cell lines are present, with different sex-chromosome allocations, individuals may develop both male and female characteristics. True hermaphrodites have both testes and ovaries, and may have both intact male and female external genital structures. Pseudohermaphrodites have external genital structures that are opposite of what would be expected on the basis of having either testes or ovaries internally. In addition, the development of the external genital structures can be incomplete, and it may initially be difficult to determine sex at birth. Occasionally, some of the male or female structures fail to form altogether for reasons that are not usually clear. In cases where external genitalia are ambiguous, it was common practice for many years to assign a female gender, and to perform surgical alterations to make the external genitals look more completely feminine. In recent years, it has been recognized that the sexual identity of genetic males after puberty is typically male regardless of whether the child was reared as a male or female, and thus more consideration is given to sex assignment now than in previous years.

Sexual determination is not always as straightforward in other species as it is in humans, and there are many different basic mechanisms by which sex is determined. In fruit flies (Drosophila melanogaster), for example, sex is determined by the ratio of X chromosomes to the number of sets of autosomes. Normal females have a ratio of 1:1, usually having two X chromosomes and two complete sets of autosomes. Males typically have one X chromosome and two sets of autosomes for a ratio of 1:2. Any ratio greater than 1.0 will result in female sex development, and any ratio below 0.5 results in male development. In between 0.5 and 1.0, the pattern of development is intermediate, bearing some aspects of both femaleness and maleness.

In most species, female development is associated with the presence of two X chromosomes, and male development with the presence of an X and a Y chromosome. Females are therefore typically the homogametic sex, meaning that their sex chromosomes are identical to one another. Males are said to be the heterogametic sex, have two different sex chromosomes. In some species, most notably in certain birds and butterflies, the male is homogametic, and the female is the heterogametic sex. In these species, the male sex chromosomes are referred to as Z chromosomes, and the females are said to have a W chromosome and a Z chromosome.

Sex determination in plants is also variable. The male-associated structures in flowering plants are the stamen and pollen. Female associated structures are the pistil and ovaries. Most plants exist as hermaphrodites, producing both male and female structures, often in the same flower. Other plants may exist as male or female individuals, producing only male or female flowers. The common sexual differentiation schemes among plants that produce seeds encased in ovaries are dioecy and gynodioecy. In dioecy, plants can be either male or female. In gynodioecy, plants are either female or hermaphroditic. Sex determination in plants is often less genetically deterministic than in humans. That is, genetic factors may not sufficiently specify the sex of the plant. This results in male, female, or hermaphroditic development being somewhat dependent on environmental conditions.

Sex determination in animals can also be heavily influenced by the environment in some species. For example, sex-determination in some species appears to be primarily dependent upon temperature at the time of development rather than on the presence or absence of specific genes or chromosomes. In certain species of fish, sexual development can change over time with individuals functioning as females for part of the life cycle and as males for other parts of the life cycle. This can be influenced by the relative abundance of individuals of the same or opposite sex in the environment, even when the other individuals are separated by an insuperable barrier such as a glass partition in an aquarium. Environmental pollutants can also influence sexual development in many species.

Bacteria are generally considered to be asexual reproducers, however, Escherichia coli sometimes contain a plasmid called the F-factor that contains 30 or so genes in a small plasmid. The presence of the F-factor permits a bacterium to conjugate with another bacterium lacking the F-factor. During conjugation, copies of the F-factor are transmitted to recipient cells, converting them from F^- to F⁺. This system is reminiscent of sexual systems in higher organisms.

There are many other unusual systems for sexual development and differentiation, and there seem to be as many exceptions as there are rules. For example, the parasitic wasp, Habrobracon juglandis can reproduce without a partner. This process is called parthenogenesis. Female wasps produce eggs at maturity and begin laying eggs regardless of whether there are males in the environment with which to mate. Both fertilized and unfertilized eggs hatch out and produce viable offspring. Eggs that are not fertilized contain only a single copy of each chromosome, a state that is called haploidy. Haploid offspring are male, and will produce sperm at maturity, and will mate with females to fertilize their eggs. The fertilized eggs receive two copies of each chromosome, one from each parent. This is called diploidy. Diploid offspring develop as females. Thus in this species, sex determination is dependent on the number of copies of each chromosome that are present at the time embryogenesis begins. When few males are present in the environment, most eggs will go unfertilized and the offspring will be haploid and thus male. When many males are present in the environment, most eggs are fertilized, giving rise to diploid offspring, which develop as females. While this system for sexual development is not common in nature, it illustrates one of the many innovative ways that sex can be determined in nature.

The benefits of sexual systems for reproduction are not very well understood in nature, but the presence of such elaborate and complex systems for development suggests that there must be benefits to sexual reproduction compared with asexual methods.

see also Anthropometry; Chromosome; Gene.

sex determination Theories and myths about what might cause a child to be boy or girl, and what action might be taken to select one or the other, have no doubt been part of all human cultures. Of those that are recorded, we know that it was a common Hippocratic view, believed by Galen, that the right testicle and the right side of the womb produced male children, and the left counterparts, female. This was disputed by Aristotle, who contended that the male determined the sex of the offspring. And he proved to be correct: the sex of a child is determined by the father's sperm.

The germinal cell from which the sperm was formed contained, like all other cells in the man's body, 22 pairs of chromosomes plus another dissimilar pair of sex chromosomes — an X and a Y. The split that resulted in sperms meant that each sperm carried one of these two alternative chromosomes: either an X or a Y, and one copy of each of the other 22 chromosomes. The mother's germinal cells had 22 pairs plus paired X chromosomes, so that every ovum had an X. Fertilization may therefore result in an embryo carrying either two X chromosomes (one from the father, one from the mother), when development will be female (XX), or an X chromosome from the mother and a Y from the father chromosome, when development will be male (XY).

How does this happen? Sometimes the inheritance of the sex chromosomes is disturbed, and this provides clues to the normal mechanism. A person with only one X chromosome and no Y chromosome (XO) develops as a female, whereas an individual with one or more X chromosomes but also at least one Y chromosome develops as a male. An experiment by the French physiologist Jost provided the basis of our understanding of the processes underlying male or female development. He operated on fetal rabbits to remove their gonads at a stage before they had developed in either a male or female direction. All fetuses from whom the testis rudiment had been removed developed as though they were female, as also did those from whom the developing ovary was removed. Thus female development is the default. It is the presence of a testis which causes male development. The testis itself develops as a result of the presence of a Y chromosome. Thus the Y chromosome determines male development by the possession of some testis determining factor (TDF).

Analysis of individual people who have either inherited an altered Y chromosome and are still female, or who apparently have 2 XX chromosomes but are male, revealed that it was only a small region of the Y chromosome which was responsible as TDF. Pieces of the Y chromosome were either missing or located in another place, and it was therefore possible to identify the gene responsible, by a positional cloning approach. At the same time as this work was progressing a mouse was discovered with a Y chromosome with a mutation that made its TDF non-functional.

Other workers isolated a candidate human gene that fulfilled all the criteria for the TDF. The scientist who had isolated the mutant mice was able to show that the equivalent gene was mutated and that its normal expression was at a critical early stage of testis development. The final proof that this was the gene responsible for sex determination came when the two groups collaborated to make mice carrying an extra copy of the human gene. These mice developed as males.

This is therefore an example of a gene which causes a switch in developmental direction. We now need to know how this gene function is turned on at the critical point of gonad development and what downstream functions it itself controls to cause male development.

Martin Evans

sex determination The mechanism by which sex is determined. In many species, sex is determined at fertilization by the nature of the male gamete that fertilizes the egg, a Y-bearing male gamete producing the male zygotes, and an X-bearing male gamete, female zygotes. In plants, this question has received considerable attention. Many plants are monoecious. In some of these, sex is influenced and perhaps determined by hormones. Only some diploid, dioecious plants (e.g. willows) have an XX/XY pattern of sex determination; some others have a single gene with 2 alleles that are concerned with sex determination. In most plants it is not clear whether primary sexual determination is under direct genetic control or is the result of a disposition (itself genetically determined) to the appropriate hormone balance for maleness or femaleness. See also SEX CHROMOSOME.

sex determination The method by which the distinction between males and females is established in a species. It is usually under genetic control. Equal numbers of males and females are produced when sex is determined by sex chromosomes or by a contrasting pair of alleles. In some species (e.g. bees) females develop from fertilized eggs and males from unfertilized eggs. This does not produce equal numbers. Environmental factors can also be crucial in governing the sex of developing individuals. For example, temperature can affect the sex ratios of broods of certain turtles. High incubation temperatures (>28°C) produce a preponderance of males, while lower temperatures (<26°C) give rise to more females.

sex determination The mechanism by which sex is determined. In many species, sex is determined at fertilization by the nature of the chromosomes in the sperm that fertilizes the egg. In some species Y-chromosome sperm produces the male (i.e. XY) zygotes and X-chromosome sperm female (i.e. XX) zygotes; in other species (e.g. birds) males are XX and females XY. See also SEX CHROMOSOME.