Chapter 2
Genes and DNA

In order to understand why the laws of inheritance work as they do, scientists had to look into the interior of cells. Cells are the building blocks of life, and all living things—from bacteria to human beings—are composed of them. The number of cells varies greatly from organism to organism: A bacterium has just one cell; an average-sized adult human has between 60 trillion and 100 trillion. Most cells are too small to be seen with the naked eye and must be viewed under a microscope. In the human body, almost all cells vary between ¹⁄25,000 of an inch and ¹⁄125,000 of an inch in diameter, although there is a nerve cell in the upper leg that, while extremely thin, is several feet long. Other cells are larger. A hen's egg, for example, is a single cell, and the largest cell of any organism on Earth is the ostrich egg, which weighs about a pound. Even the smallest cell contains a complete copy of the genetic information that gives an individual organism the traits that make it what it is and not some other thing. Cells have what are called life cycles. They are created, live, reproduce, and die. It is during the process of reproduction, or cell division, that genetic information is passed along from generation to generation.

Simple and Complex Cells

There are two types of cells, prokaryotes and eukaryotes. (The words are pronounced "pro-carry-oats" and "you-carry-oats.") Prokaryotes are the kind of cells of which bacteria and other single-celled organisms are composed. More complex forms of life, including plants and animals, are made of many eukaryotes. The two types of cells are distinguished from each other by their internal structure. Both are enclosed within an external membrane that separates them from their environment. All the internal components of a prokaryote float within this membrane. Eukaryotes, on the other hand, have a number of additional internal membranes that divide them into compartments.

The principal compartments of a eukaryotic cell are the nucleus and the cytoplasm. To use an analogy from the world of business, the nucleus is the cell's executive office and the cytoplasm is its factory. The nucleus generates instructions for a number of cellular processes that are, in turn, carried out in the cytoplasm. The nucleus of a eukaryotic cell is itself a complex structure. It is composed of DNA (deoxyribonucleic acid), which contains genetic information and combines with proteins to produce a substance called chromatin.

"Throughout most of the life cycle of the cell, chromatin exists as exceedingly long, thin, entangled threads that cannot be clearly distinguished by any microscope," says geneticist William K. Purves.

However, when the nucleus is about to divide, the chromatin condenses and coils tightly to form a precise number of readily visible objects called chromosomes. Each chromosome contains one long molecule of DNA. The chromosomes are the bearers of hereditary instructions; their DNA carries the information required to perform the functions of the cell and endow the cell's descendants with the same instructions.⁸

The number of chromosomes in each cell varies from organism to organism, but they always come in matched pairs called homologues. Human beings have 23 pairs of chromosomes for a total of 46. Chimpanzees, humanity's closest relative in the animal kingdom, have 24 pairs; dogs have 39; cats, 17; ferns, 256. Thus, in humans, the genetic information contained in DNA is divided among 23 pairs of homologous (matching) chromosomes in such a way that the nucleus of each individual cell contains a complete copy of the organism's entire genetic code. Each chromosome is a long molecule which is further divided into subsections of genetic information. These subsections are the factors that Mendel discovered—what today we call genes.

Chromosomes, DNA, and Genes

Although the chromosomes contain a copy of an individual's genetic makeup—all the genes necessary to produce all the individual's traits—the two members of each matching set of chromosomes are not exactly identical to each other. This is because one set of chromosomes is inherited from the maternal parent and its matching partner from the paternal parent. Thus, it is possible for homologous chromosomes to contain different alleles for the same gene. In Mendel's experiments with peas, with respect to height some of his plants contained two dominant alleles for tallness, some contained two recessive alleles for shortness, and some contained both a dominant and recessive allele.

This fact is crucial for an understanding of genetic inheritance. It explains why children are not identical to one or the other of their parents. It also explains why parents can pass on the genes for recessive traits, traits that they do not themselves exhibit, to their progeny and why a specific trait may lie dormant for generations before making its appearance in a family tree. That matching homologous chromosomes can contain different alleles for the same gene accounts for the pervasive fact of genetic diversity—how from a relatively limited number of genes a virtually unlimited number of unique individuals can be produced.

Science writer Laura Gould sums up the role of the cell nucleus and its contents in the production of the traits that distinguish one individual from another:

Chromosomes are thread-like structures in the nucleus of almost every cell [some red blood cells don't have a nucleus]; they are made in part of DNA. They come in matching pairs, one member of the pair providing genetic information from the mother, the other from the father. . . . Genes are just little pieces of chromosomes: tiny segments of DNA. . . . Each gene has a fixed location on its chromosome and helps to specify a trait.⁹

Genes determine traits because they function as a code that tells structures in the cytoplasm how to function. The cytoplasm is found outside the cell's nucleus. A computer analogy is useful: The DNA contained in genes performs like software, telling the hardware in the cytoplasm what to do. Specifically, it sends a message through the membrane that encloses the nucleus to entities called ribosomes in the cytoplasm to manufacture one or several of a wide range of proteins. It is these proteins that actually do the work of making peas tall or short, or humans brown-eyed or blue-eyed.

The Genetic Alphabet

DNA was discovered in 1869 by a German scientist named Friedrich Miescher. He found it while studying pus that had accumulated on the bandages of wounded soldiers. Miescher, along with other scientists, learned that DNA was a large molecule composed mostly of a type of sugar called deoxyribose, which is related to table sugar. They also found traces of phosphate, a chemical derived from the element phosphorous. But the most important discovery was that DNA also contained four substances called nucleotide bases. These bases are adenosine, cytosine, guanine, and thymine, and they are abbreviated A, C, G, and T.

Miescher suspected that these bases combined to form chemical messages, and in so doing he came close to discovering the genetic code that governs all life. In fact, later research has shown that the bases that compose DNA function exactly like an alphabet that encodes meaningful expressions. In the same way that the twenty-six letters of the English alphabet can be combined to form an enormous number of intelligible words, phrases, and sentences, the four letters of the genetic alphabet—A, C, G, and T—combine with each other to create chemical messages that are then transmitted to the ribosomes and other parts of the cell.

However, for a language to work as a method of communication, the various letters have to be associated with each other according to a set of rules. In human languages, these rules are called grammar and syntax. The genetic code also has a set of rules, but it took scientists a long time to discover exactly what it was. The first clue came in the early part of the twentieth century when they found that in any DNA molecule the number of As must equal the number of Ts and the number of Cs must equal the number of Gs, but the number of A-T, C-G combinations does not have to be equal.

The importance of this piece of information, however, was not understood for almost fifty years until scientists developed a complete description of how the various components of a DNA molecule fit together. This feat was accomplished by a process called X-ray crystallography, in which a substance is combined with salt and allowed to form crystals. When these crystals are viewed under a powerful electron microscope, the structure of molecules becomes apparent. However, electron microscopes do not produce precise visual images of what they are focused on. Instead, they generate data that have to be interpreted.

The Structure of DNA

In the 1940s, two British scientists, Rosalind Franklin and Maurice Wilkins, applied the techniques of X-ray crystallography to DNA. Two other scientists, American geneticist James Watson and British biophysicist

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Francis Crick, became aware of their work and began to construct a physical model of the DNA molecule. The 1953 paper in which Watson and Crick published the results of their painstaking research has been recognized as one of the most revolutionary and influential documents in the history of science.

Watson, Crick, and Wilkins each received a Nobel Prize for their work. Unfortunately, Franklin died before her invaluable contribution could be recognized in this way. Recently, historians of science have finally begun to recognize that without Franklin's groundbreaking work, the discovery of the structure of the DNA molecule would have been delayed by years, if not decades.

Watson and Crick concluded that the DNA molecule was shaped like a double helix, two strands spiraling around each other. Former New York Times science editor Boyce Rensberger explains:

A helix is the shape of a corkscrew. A double helix is the shape of two corkscrews, one intertwined with the other and curving parallel to it, like the railings of a spiral staircase. Another way to think of the double helix is to imagine a twisted rope ladder with rigid rungs, each rope forming a helix. The easiest way to think about DNA is to start by splitting the two helices [the plural form of the word helix] apart. Think of it as sawing down through the middles of the wooden rungs of a rope ladder. The result is two single ropes with half-rungs hanging off each rope.¹⁰

Watson and Crick's discovery of the double helix structure of DNA unlocked the secret of the rules that govern the genetic code. In every DNA molecule each A is associated with a T and each C with a G. "In all DNA the rope part of the ladder is the same up and down its length—a monotonous alteration of sugar and phosphate molecules," Rensberger continues. "The half-rungs, which stick out from the sugars, are the interesting parts. They serve as the four letters of the genetic alphabet. . . . As in the English language, the sequence of bases along one strand of DNA—the sequence of As, Ts, Cs, and Gs—spells out the genetic message. . . . Opposite every T would be an A (and vice versa) and opposite every G would be a C (and vice versa)."¹¹ Extending the comparison between the genetic code and human language, a gene, as a sequence of As, Ts, Cs, and Gs along the entwined strands of DNA that make up a chromosome, becomes the equivalent of a sentence.

The question then arises: How can just four letters create code for the thousands of proteins that the body produces and the correspondingly large number of traits they govern? The answer lies in the astonishingly large number of A-T, C-G combinations, or base pairs as they are called, that make up a gene. If all the DNA compacted into a cell were stretched out, it would be about seven feet long. Thus, says R. Scott Hawley, "The average human DNA molecule is 65 million base pairs in length for a total DNA content of six trillion base pairs."¹² So, although the four genetic letters can be put together in only a few unique ways, the fact that each pairing on the 6 million rungs of the DNA ladder can be different from creature to creature or plant to plant accounts for the complexity of life.

DNA and RNA

The sequences of DNA that make up genes communicate instructions to the ribosomes to manufacture proteins that work together to produce an organism's traits. However, genes do not perform this function directly. First, a process called transcription must occur. In transcription, a single gene, which could contain thousands of base pairs, unravels from the chromosome on which it is located. The DNA that constitutes that gene then splits into its two complementary strands. A special type of protein called an enzyme moves along one of the strands letter by letter and creates a corresponding strand of a substance called ribonucleic acid (RNA).

RNA is similar to DNA in that it that it has four nucleotide bases. Three of these bases—A, C, and G—are the same in both, but in place of thymine (T), RNA has a base called uracil, which is abbreviated with the letter U. As the enzyme creeps along the gene's DNA, it transcribes each base it encounters into a corresponding base on the newly emerging strand of RNA. Thus, a C on the DNA strand becomes a G on the RNA strand, a G becomes a C, a T becomes an A, but the As are transcribed not into Ts but into Us. For example, a strand of DNA that reads ACGGCAT would be transcribed as UGCCGUA.

Once the strand of RNA has been completely transcribed, it travels through the membrane that encloses the cell's nucleus into the cytoplasm. There, it attaches itself to a ribosome, providing the instructions needed to manufacture a protein. This process is called translation, and it works like this. The thousands of proteins that any organism contains are made up of various combinations of twenty substances called amino acids. Each three-letter sequence of RNA tells the ribosome to make one of these amino acids. The process continues in sequence, each three letters of RNA bringing into existence a new amino acid, which attaches itself to those already made. At the conclusion of the process, a complete protein has been manufactured and is ready to do its part in producing the traits that characterize the organism in which all this activity has been taking place.

The three-letter sequence of RNA that codes for an amino acid is called a condon. Together, the condons form a set of instructions—the genetic code mentioned earlier. This code is the basis for all the forms that life can take. It bridges the gap between the hereditary information that genes contain and the biochemical processes that give each individual organism the traits that define it.

Mitosis

The way genes encode instructions for the manufacture of proteins is similar to the mechanism they use to pass from generation to generation. A key part of the life cycle of every cell takes place when the cell reproduces, or makes a copy of itself. Eukaryotic cells, those that make up complex organisms like plants and animals, come in two types. These types are somatic cells and sex cells, also called gametes. Somatic cells combine with each other to make up a body's tissues and organs. Sex cells combine with the sex cells of another organism to produce offspring.

The two sorts of eukaryotes reproduce in different ways. When somatic cells divide, they include a complete copy of all the genetic information contained in the original cell. That is, both corresponding sets of chromosomes are replicated in the new cell. On the other hand, when sex cells divide, only one of the two sets of chromosomes is reproduced. When the sex cell combines with the opposite sex cell of another organism—a sperm cell with an egg cell—the new cell produced by this union will then contain two matching sets of chromosomes, but one will have come from the father and the other will have come from the mother.

The reproduction of somatic cells is called mitosis; that of sex cells is termed meiosis. The purpose of mitosis is growth, so that organs and other body parts can form completely as an organism progresses from infancy to adulthood. Mitosis also creates new cells to replace those that die off at the end of their life cycles. The purpose of meiosis is to create an entirely new organism.

Compared to meiosis, mitosis is a relatively straightforward process. First, the chromosomes become thicker and double into cross-shaped forms, each limb of the cross containing a complete copy of the DNA in all of the organism's genes. Biochemists Paul Berg and Maxine Singer describe how the phenomenon continues: "All of the chromosomes eventually line up in the central plane of the cell and then divide into two groups; the two groups then move to opposite ends of the cell. Two cells are formed when a membrane grows and separates the two ends of the original cell. Each of the new cells (referred to as daughter cells) has a full set of chromosome pairs."¹³

Meiosis

Because sex cells combine to form a new organism, they cannot each have a full complement of matching chromosomes. If they did, the offspring resulting from the union of two sex cells would have twice the number of chromosomes—and twice the amount of genetic information—as either of the two parent cells. In humans, for example, each child would have not the required forty-six chromosomes but two times that number, or ninety-two. Human offspring with more or less than the necessary forty-six chromosomes usually do not survive; consequently the human race would have died out after the first generation.

Therefore, sex cells divide twice. The first division is like mitosis, except that during the stage when the number of chromosomes doubles, individual genes often jump from one chromosome to the other. This is possible because similar genes occur at the same location on each of the chromosomes. The process, known as crossing over or recombination, plays a key role in genetic engineering and also promotes genetic diversity. Since one member of each pair of chromosomes has been inherited from the mother and the other from the father and since each gene has two forms (alleles), recombination creates a novel arrangement of genetic information to be passed on to future generations.

Once the chromosomes have doubled and two new cells have been formed, a further division takes place to guarantee that each sex cell produced has only one set of chromosomes (in humans, twenty-three rather than forty-six). "These two paired sets of recombined chromosomes now separate in the phase known as meiosis-II, or reduction division," says Colin Tudge. "Without further doubling of chromosome material, each pair of chromosomes from each set separates from its homologue [matching partner]. Meiosis results in four cells, each . . . containing just one set of chromosomes, and each of those chromosomes is a unique new entity, combining genetic material from both parents."¹⁴

When each individual sex cell meets up with its partner of the opposite sex during reproduction, a new cell is formed that contains the chromosomes, and the recombined genes on those chromosomes, from each of the parent cells. Thus a new creature is created. It is similar to its parents because it has the same genes as they did, but it is also different because each of those genes may contain alleles different from the ones that constituted the genetic makeup of the parents. As this process continues from generation to generation, the individuals produced tend to differ to an ever-greater degree from the original parent pair. These differences enable subsequent generations to adapt to changing environment and form the genetic basis of evolution, explaining how species have changed, and new species have arisen, during the course of the history of life on Earth.

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Sex Determination

There is one exception to the rule that all chromosomes come in matching pairs, and that exception determines whether newly conceived organisms develop into males or females. The pair of dissimilar chromosomes have been designated X and Y. It is important to remember that although they have different names, they do form a pair in the same way their more alike counterparts do. The Y chromosome is shorter than the X. That is just another way of saying that it has fewer genes, or less genetic material. But it does contain one gene that the X does not, and that is the TDF gene—the gene that causes maleness.

Every normal human female has two X chromosomes; every normal male has both an X and a Y. (There are variations to this rule in some other types of organisms.) When eggs, the female sex cells, are formed during the first stage of meiosis, each one gets two copies of the X chromosome. When sperm cells are formed, each gets an X and a Y. When these cells divide again during the second stage of meiosis to create a cell with only one copy of each chromosome, the egg must have an X and only an X because that is all it had to start with. A sperm cell can have either an X or a Y.

When egg and sperm combine during the conception of a new individual, the cell that is produced must therefore inherit one X chromosome from its mother. From its father, however, it can inherit either an X or a Y. Whether a sperm cell has an X or a Y chromosome is random, accounting for the roughly equal number of males and females born.

For the first six weeks of life, the human embryo, whether it is to become a male or female, develops in the same way. Sometime during the seventh or eighth week of pregnancy, the TDF gene provided by the Y chromosome, if there is one, becomes active. During this period of activity, which lasts only during this phase of the embryo's growth, the gene sends chemical instructions to other genes, telling them to produce the proteins that will cause certain cells to mature into male testicles. The testicles produce hormones which create other male sexual characteristics. If only X chromosomes are present, this process does not occur and the embryo develops into a female.