Genetics is the area of biology concerned with the study of inheritance, the process by which certain characteristics of organisms are handed down from parent to offspring. Modern genetics began in 1865, when the Austrian monk Gregor \TMendel\t demonstrated the inheritance patterns of the garden pea, Pisum savitum, and provided a new way of looking at \Theredity\t. Mendel's theories were based on hereditary factors, or genes (see \Tgene\t), the existence of which he deduced without seeing them or having any notion of what they were or where they were located. Gregor Mendel's results and theories, however, went unnoticed until 1900, when Hugo De Vries in the Netherlands, Carl Correns in Germany, and Erich von Ischermak-Seysenegg in Austria--who almost simultaneously rediscovered Mendel's work and independently performed similar experiments--arrived at the same conclusions reached by Mendel. It is now known that genes dictate the characteristic structures and functions of all organisms, from viruses to redwood trees and elephants, and that these characteristics are in turn passed on from parent to offspring. It is also known that the variety of hereditary traits are caused by variations in the genes themselves. MENDEL'S EXPERIMENTS Mendel studied seven characteristics of the garden pea and obtained experimental results that suggested a similar hereditary mechanism for all. In one experiment, he crossed plants that differed in the characteristic of plant height. He had previously obtained a line of pea plants that always produced tall plants and a line that always produced short plants, and he crossed them by transferring pollen from one plant to another. He found that the progeny (the first filial generation) were all tall. He then allowed these to self-pollinate and produce another generation of progeny (the second filial generation), three-quarters of which were tall and one-quarter short. Mendel's Laws From these results, Mendel deduced an explanation for the mechanism of inheritance and assumed certain principles to be true: (1) hereditary factors (genes) must exist; (2) two factors exist for each characteristic; (3) at the time of sex-cell formation, the hereditary factors of a pair separate equally into the gametes (law of segregation); (4) the gametes bear only one factor for each characteristic; (5) hereditary factors for different traits sort independently of one another at gamete formation (law of independent assortment); and (6) gametes join randomly, irrespective of the factors that they carry. The characteristic that appeared in the first generation plants--in this case, tall plants--seemed to dominate over the one that did not appear. Mendel called tallness a dominant trait and shortness recessive; this phenomenon was referred to as the law of dominance. A capital A is now usually used to represent the gene that determines the dominant character, and a small a for one that determines the recessive character. When a pair of hereditary factors, or genes, are of the same type (AA), the condition is said to be homozygous for that character. On the other hand, if the two members of a pair are different (Aa), the condition is called heterozygous. The second generation plants of Mendel's experiment were composed of one-quarter AA, one-half Aa, and one-quarter aa. Since tallness is dominant, AA and Aa both appear tall, accounting for the three-quarter: one-quarter ratio of tall to short. The alternate forms of a gene, known as alleles, combine to produce different genetic types, or genotypes. Mendel demonstrated that the three-quarter: one quarter ratio existed for all seven characteristics of peas that he studied; he also showed that the separate gene pairs behaved independently of each other during gamete formation. CHROMOSOMES Mendel's knowledge of genes and their behavior was entirely theoretical. Subsequent studies of \Tcell\t structure and cell division have supplied physical evidence supporting his theories. It is now generally believed that genes behave as they do because of their location on chromosomes (see \Tgenetic code\t), structures found in the nucleus of each \Tcell\t of an organism. Chromosomes are not all the same length, and, when stained in the appropriate way, each may show characteristic bands, thickenings, or constrictions. The cells of each species contain a fixed and characteristic number of chromosomes. Some organisms, such as fungi and single-celled algae, have only a single set, or haploid number (n), of chromosomes in their cell nuclei. The somatic cells of most higher organisms, including humans, contain two sets, or a diploid number (2n), of chromosomes. Still other organisms, such as mosses, ferns, and horsetails, alternate between diploid and haploid during different stages of their life cycles. Meiosis In diploid cells, gene pairs are located at specific sites (loci) on each chromosome. These gene pairs can be composed either of two identical genes or two alleles. A diploid cell therefore contains two genes for each hereditary characteristic. The gametes (sex cells) of diploid organisms, however, contain only a haploid (n) number of chromosomes; the union of two gametes, one from each parent, produces a diploid (2n) zygote, from which the offspring develops. The process of cell division by which such gametes are produced is called meiosis. It takes place in the testes and ovaries of animals, in the anthers and ovaries of higher plants, and in the sporophyte (2n) stage of organisms that alternate between haploid and diploid. In meiosis a single diploid cell divides into two diploid cells, each of which divides into two haploid cells. During this process, the two sets of chromosomes separate, thereby separating the members of the gene pairs. Each of the four resulting gametes therefore contains only one gene for each characteristic, and different gametes from the same parent may carry different alleles. Mendel's postulates may therefore be restated in physical terms as follows: (1) genes are located on chromosomes; (2) genes occur in pairs, occupying specific loci on a chromosome pair; (3) the first meiotic division separates the chromosome pairs, producing an equal division of the members of a gene pair in the product cells; (4) since there are two cell divisions and only one replication of chromosomes, the chromosome number is halved; (5) different gene pairs on separate chromosome pairs behave independently of each other; and (6) collision of egg and sperm is a chance process. Linkage and Crossing-Over In the early 1900s, Thomas Hunt \TMorgan\t used the fruit fly Drosophila melanogaster to test a situation that Mendel did not encounter, in which two gene pairs are located on the same chromosome pair. In this case they do not behave independently, since genes on the same chromosome tend to stay together during meiosis. This is called linkage. The combinations can be separated by the simultaneous breaking of homologous chromosomes during the first meiotic division, and the joining of the broken segments from each chromosome to the homologous broken segments. This process, called crossing-over, occurs regularly during meiosis and randomly between any chromosome pair in a bundle of four. Crossovers can be detected genetically if they involve two heterozygous gene pairs (the alleles producing distinct gene products). Under a microscope, they appear as cross-shaped structures called chiasmata. Mapping Crossing-over can be used to produce a chromosome map showing the relative positions of the loci of the known gene pairs. Two organisms having homozygous gene pairs are bred, and the offspring (first generation) has heterozygous gene peirs (AaBb). This heterozygote is then crossed with a tester strain of the genotype aabb, a standard tool known as a testcross. The progeny of a testcross are screened for the appearance of the genotype Aabb and aaBb, which can only arise from crossovers. The frequency of these types is a standard measure and is assumed to be proportional to the distance between the two loci on their chromosome. Using different combinations of gene pairs, an internally self-consistent map can be constructed in which the number of map units is defined as the percentage of progeny in a testcross derived from a crossover. The Role of Chromosomes It is now known that genes are lengths of a threadlike chemical called deoxyribonucleic acid (\TDNA\t) and form a continuous string that constitutes the chromosomes. Several researchers have attempted to explain the significance of the long assemblages of genes in chains, or chromosomes. First, some combinations of genes have adaptive value and need to be inherited as a package. Having them linked closely on one chromosome is one way of ensuring this. Second, genes with related functions often need to be activated simultaneously; their proximity allows them to be activated by one common switch mechanism. Third, the packaging of genes into units facilitates the orderly production of daughter cells in cell division. Crossing-over and independent assortment of genes result in combinations of genes in progeny that are different from the parental arrangements. This process, called recombination, is believed to be an important mechanism for generating new genotypes. Recombination most frequently occurs among genes widely separated from each other; closely linked genes, however, have a random chance of rearrangement. POLYGENES AND GENE-ENVIRONMENT INTERACTION Mendel explained the phenomenon of discontinuous hereditary variation, which is expressed in separate and distinct forms that are associated with one kind of allele, such as tall versus short or wrinkled versus smooth. Continuous variations occur in many phenotypes, however, such as length or weight, is also commonly observed in nature and forms an apparently unbroken range from one extreme to another. This phenomenon, known as polygenic inheritance, results from the complex interaction among a set of genes. Human skin color, shades ranging from black through brown and yellow to white, is a good example of a trait determined by polygenes. Only an infinite number of polygenes, however, could give a perfectly continuous variation. The phenotype of an organism is shaped not only by its genotype but also by the interaction of that genotype with the environment. It is often difficult to determine the relative contribution of genetic and environmental variation to a particular phenotype. SEX DETERMINATION The sex of an organism is usually an inherited phenotype. In haploid forms, alleles of one gene pair can determine sex, but in higher organisms sex is often associated with a special pair of chromosomes called sex chromosomes. For example, human cells contain 22 pairs of autosomes, or nonsex chromosomes, and one pair of sex chromosomes. Women possess two identical sex chromosomes (X and X), and men possess two different sex chromosomes (X and Y). The presence or absence of the Y chromosome determines sex in humans; therefore, the Y contains the genes for male sex determination, called the "testis determining factor" (tdf). In many higher plants, anthers and ovaries are located on separate plants (dioecism), and some of these have an X/Y-like chromosomal determination of sex. In humans, the X chromosome bears genes that affect traits having nothing to do with the sex. Because they are located on the X, however, they show a special inheritance pattern different from autosomal gene inheritance; the Y chromosome apparently has no counterpart to these genes. Red-green color blindness and hemophilia are two genetic traits determined by X-linked genes. The X and the Y genes are able to separate into equal numbers of sperm in the male and produce a 1:1 ratio of males to females in the eggs that they fertilize. THE NATURE OF THE GENE The genetic material for most organisms, \TDNA\t, is a double-stranded helix comprising a long chain of nucleotide bases with a sugar-phosphate backbone, as proposed by James D. \TWatson\t and Francis H. C. \TCrick\t in 1953. Eukaryotic cells contain two kinds of \TDNA\t sequences: unique \TDNA\t, one copy present in a haploid gene set; and repetitive \TDNA\t, identical copies (one million or more) found dispersed throughout the chromosome. The unique segments probably contain regular genes. The function of repetitive \TDNA\t segments is not known, although they may be involved either in the process of chromosome pairing or in regulating the activity of the unique sequence. \TDNA\t of eukaryotic organisms appears to be wound around nucleosomes--small, beadlike units that each consist of about 200 base pairs of \TDNA\t and a complex structure of proteins known as histones. Nucleosomes help package the \TDNA\t into the chromosome--an average human chromosome is about 0.005 mm in length and contains 50 mm of \TDNA\t. During mitotic cell division chromosomal replication produces two identical daughter cells, each of which contains identical \TDNA\t, assuring the stability of the hereditary material. The \TDNA\t replication is semiconservative. This means that free nucleotides hydrogen-bond to each half of the separate \TDNA\t strands, resulting in two new \TDNA\t double helices each consisting of one-half old and one-half newly formed strands. Genes of the \TDNA\t in eukaryotic organisms (\TRNA\t in some viruses) control phenotype by coding for the structure of \Tproteins\t, which are the main structural and catalytic molecules in an organism; hair, muscle, skin, tendons, and enzymes are all proteinaceous. The order of the nucleotide bases in \TDNA\t dictates the corresponding order of amino acids that give proteins their specific shape and function during \Tprotein\t \Lsynthe\lsis. The protein-building information in \TDNA\t is copied into a single-stranded molecule, called messenger \TRNA\t (m\TRNA\t), that then moves to the cytoplasm, where protein synthesis occurs. The nucleotides in m\TRNA\t can be thought of as letters that are read in groups of three, called codons, each codon standing for an amino acid. The amino acids are transported to the m\TRNA\t by transfer \TRNA\t molecules, and the protein is assembled on the surface of ribosomes. In humans the \TDNA\t in each cell contains about 3 billion base pairs, distributed among 22 sets of autosomal chromosomes and one set of sex chromosomes in the nucleus as well as one set of chromosomes in each mitochondrion. If all of this \TDNA\t were stretched out, it would have a length of about 1 m (3 ft), but the \TDNA\t is tightly compressed into the chromosome. Only about 2 percent of a person's \TDNA\t forms the actual genes, as well; the rest constitutes either noncoding "spacer" regions between genes or noncoding "intron" regions within genes. The amount of \TDNA\t per cell varies tremendously within both animal and plant kingdoms and is unrelated to the taxonomic group concerned (see \Tgenetic code\t; \Tgenome\t). MUTATION \Tmutation\t is the process by which genes change from one form to another. Mutations may be caused by such mutagens as X rays, ultraviolet rays, nitrous acid, ethyl methane sulfonate, and nitrosoguanidine; less frequently, mutations may occur spontaneously as a result of accidental changes in the chemistry of the cell. Because mutation is random, haphazard change, most mutants contain damaged genes that are nonfunctional. Mutants usually do not live long in nature; geneticists and breeders, however, may keep mutants alive for study or for use in producing new plant and animal forms in agriculture. A mutation in \TDNA\t usually results in an altered nucleotide sequence, either by substitution, addition, deletion, or insertion, which is translated into an altered amino-acid sequence that usually produces a change in the organism's normal body function. The alteration of amino acids can have a drastic effect on function, as in the case of sickle-cell hemoglobin. A mutation of the chromosome by transposition, translocation, or insertion can cause similar effects. Mutations of cells other than sex cells are considered to be a primary cause of cancer in those tissues. All humans carry quite a large number of deleterious and lethal mutant genes that are recessive. Each mating is a kind of a lottery, in which the offspring reveal whether or not the parents' mutations are at identical loci. For example, if both parents are heterozygous (Aa) for a gene pair in which the recessive allele is deleterious, then one-fourth of their children will show genetic disease of the kind controlled by that locus. Genetic counseling can often help prospective mates in determining whether such diseases will manifest in their offspring (see also \Tgenetic imprinting\t). GENES IN DEVELOPMENT Most organisms start life as single cells (zygotes) and grow into massive multicellular bodies with cells of considerable differences in form and function. This process, which involves growth and differentiation, is called \Tdevelopment\t. Although skin cells, liver cells, brain cells, and so on, are highly differentiated, they are all derived from the original zygote as a result of the high-fidelity copying of \TDNA\t during mitotic division. This is achieved by a complex, little-understood process whereby different genes are active in different tissues. The best examples of gene regulation are found in bacteria, where genes of related function are grouped on the chromosome together with a special class of regulatory genes to form an operon, which is a kind of control unit. The operon theory was proposed by Francois Jacob and Jacques Monod in 1961. Regulatory genes, usually responding to environmental cues, either assist or prevent the passage of the m\TRNA\t synthesis enzyme, \TRNA\t polymerase, along the operon, thereby controlling gene activity. No satisfactory examples of operons have been found at present in higher organisms, but several examples of regulatory genes are known, although these are not necessarily linked to a controlled locus. Repetitive \TDNA\t that is interspersed between unique \TDNA\t has been postulated as a site of a vast system of regulatory genes. GENES IN CYTOPLASMIC ORGANELLES Although most genes are found in the chromosomes of the nucleus, two kinds of cytoplasmic organelles, mitochondria and chloroplasts, also contain certain genes. Phenotypes determined by these genes are inherited through the female parent. Maternal or uniparental inheritance has been extensively studied in microorganisms, notably the unicellular algae, chlamydomonas, and several fungi. In Chlamydomonas, a variety of drug-resistant and morphological phenotypes are involved. In fungi, sensitivity to certain drugs, such as erythromycin, paramomycin, and oligoomycin, can be cytoplasmically inherited, as can some kinds of poor growth phenotypes ("petites" in yeast and "poky" in the bread mold Neurospora). The mitochondria and chloroplasts carry their own \TDNA\t, which is circular and unlike nuclear \TDNA\t in nucleotide composition. They also contain their own autonomous protein-synthesizing system, many parts of which are coded by organellar \TDNA\t genes. Many other components of the mitochondria and chloroplasts, such as cytochromes, are coded by genes of nuclear \TDNA\t. These organelles are therefore composed of a mixture of components with \TDNA\t blueprints located in both the nucleus and the organelle. The specific synthesizing machinery of mitochondrion, together with its shape and size, have suggested to some that the mitochondrion is a vestige of a primitive symbiotic association with bacteria. Similarly, the structure and functions of a chloroplast are reminiscent of the primitive blue-green algae. This kind of evolution, in which complexity results from the adoption of an internal collection of simpler cells, is called hereditary symbiosis and may have been important in the development of modern cells. GENES IN POPULATIONS Mendelian genetics can predict the inheritance patterns within families, but one should not expect to see similar patterns and ratios in populations, which are complex mixtures of different families. A different approach, sometimes called population genetics, is used to analyze genetic distribution in populations. Each locus contains two alleles (A and a) of one gene. The gene pool of a population is derived by considering each diploid individual to be one cell bearing two genes at that locus. The total number of A and a genes in a population is calculated and an allele frequency for each is obtained. Usually, the frequency of A is called p, and the frequency of a is called q, where p + q = 1 (or 100%). The allele frequencies are the main determinants of the genetic structure of populations. If mating is random for example, there will be pp of AA, 2 pq of Aa, and qq of aa. This genotype distribution, which is stable if all other factors are constant, is called Hardy-Weinberg equilibrium, named after its discoverers. At its most fundamental level, evolution is little more than a change in relative allele frequencies. The actual values of p and q at each locus are determined by the complex interaction of many forces, including mutation from A to a, mutation from a to A (reversion, which is usually less frequent than forward mutation), chance fluctuation due to small populations (producing genetic drift of allele frequencies), and natural selection for or against certain genotypes. In turn, selection can be directional, ultimately eliminating one allele from the population, or stabilizing, favoring intermediate genotypes and tending to maintain several alleles and phenotypes in an interbreeding population, a phenomenon called genetic polymorphism. Preliminary results of a different form of genetic study of human evolution aroused controversy at the 1987 meeting of the American Anthropological Association. The research involved analyses of mitochondrial \TDNA\t in placental samples from women with a worldwide distribution of ancestry. Such \TDNA\t is inherited only from the mother, and through mutation studies the researchers hoped to trace human ancestry back to a "single" source--some generation of first humans. The results of a team of geneticists working at the University of California, Berkeley, suggested a human family tree with roots in sub-Saharan Africa some 140,000 to 200,000 years ago. Another team, at Emory University, proposed a common ancestor of similar age but in southeastern Asia. Anthropologists expressed considerable skepticism, however, about these results of what came to be known as the "Eve" hypothesis. Most anthropologists consider that the first true humans appeared much longer ago (see \Tprehistoric humans\t). MODERN GENETICS Genetics is an important aspect of many areas of pure and applied biology. Viral genetics, microbial genetics, plant genetics, animal genetics, and human genetics focus research on specific types of organisms. Research in molecular genetics involves studies on chemical structure and function; cytogenetics on location of the genetic material in cells and on cell division; developmental genetics on the genetic function in embryological phenomena; behavior genetics on the role of the gene in regulating behavior; and population genetics on the evolutionary process. At the applied level, genetics is of direct use in understanding genetic diseases and environmental mutation. It is used in plant and animal breeding to improve the quality and quantity of food. It also is a tool in basic research by which complex biological processes can be analyzed, often at the molecular level. A. J. W. Griffiths Bibliography: Ayala, F. J., Population and Evolutionary Genetics (1982); Briggs, David, and Walters, Max, Plant Variation and Evolution (1969); Burnet, Frank Macfarlane, Endurance of Life: The Implications of Genetics for Human Life (1978); Dobzhansky, Theodosius, Genetics of the Evolutionary Process (1970); Goodenough, U., Genetics, 3d ed. (1983); Lerner, I. Michael, and Libby, William J., Heredity, Evolution, and Society, 2d ed. (1976); Levine, Louis, Biology of the Gene, 3d ed. (1980); Lewontin, R. C., Rose, Steven, and Kamin, L. J., Not in Our Genes: Biology, Ideology and Human Nature (1984); McKusick, V. S., Mendelian Inheritance in Man, 7th ed. (1986); Mertens, Thomas R., ed., Human Genetics: Readings on the Implications of Genetic Engineering (1975); Scandalious, J. G., Molecular Genetics of Development (1987); Smith, Anthony, The Human Pedigree (1976); Spiess, E. B., Genes in Populations (1977); Suzuki, David T., and Griffiths, A. J., An Introduction to Genetic Analysis, 3d ed. (1986); Stent, G. S., and Calendar, R., Molecular Genetics (1978); Watson, James D., The Double Helix (1968); Watson, J. D., et al, The Molecular Biology of the Gene, 2 vols. (1987).