1.2 Genetic variation

If all members of a species have the same set of genes, how can there be genetic variation? As indicated earlier, the answer is that genes come in different forms called alleles. In a population, for any given gene there can be from one to many different alleles; however, because most organisms carry only one or two chromosome sets per cell, any individual organism can carry only one or two alleles per gene. The alleles of one gene will always be found in the same position along the chromosome. Allelic variation is the basis for hereditary variation.

Types of variation

Because a great deal of genetics concerns the analysis of variants, it is important to understand the types of variation found in populations. A useful classification is into discontinuous and continuous variation (Figure 1-10). Allelic variation contributes to both.

DISCONTINUOUS VARIATION Most of the research in genetics in the past century has been on discontinuous variation because it is a simpler type of variation, and it is easier to analyze. In discontinuous variation, a character is found in a population in two or more distinct and separate forms called phenotypes. “Blue eyes” and “brown eyes” are phenotypes, as is “blood type A” or “blood type O.” Such alternative phenotypes are often found to be encoded by the alleles of one gene. A good example is albinism in humans, which concerns phenotypes of the character of skin pigmentation. In most people, the cells of the skin can make a dark-brown or black pigment called melanin, the substance that gives our skin its color ranging from tan color in people of European ancestry to brown or black in those of tropical and sub-tropical ancestry. Although always rare, albinos, who completely lack pigment in their skin and hair, are found in all races (Figure 1-11). The difference between pigmented and unpigmented skin is caused by different alleles of a gene that encodes an enzyme involved in melanin synthesis.

The alleles of a gene are conventionally designated by letters. The allele that codes for the normal form of the enzyme involved in making melanin is called A, and the allele that codes for an inactive form of that enzyme (resulting in albinism) is designated a, to show that they

are related. The allelic constitution of an organism is its genotype, which is the hereditary underpinning of the phenotype. Because humans have two sets of chromosomes in each cell, genotypes can be either A/A, A/a, or a/a (the slash shows that the two alleles are a pair). The phenotype of A/A is pigmented, that of a/a is albino, and that of A/a is pigmented. The ability to make pigment is expressed over inability (A is said to be dominant, as we shall see in Chapter 2).

Although allelic differences cause phenotypic differences such as pigmented and albino coloration, this does not mean that only one gene affects skin color. It is known that there are several, although the identity and number of these genes are currently unknown. However, the difference between pigmented, of whatever shade, and albinism is caused by the difference in the alleles of one gene—the gene that determines the ability to make melanin; the allelic composition of other genes is irrelevant.

In some cases of discontinuous variation, there is a predictable one-to-one relation between genotype and phenotype under most conditions. In other words, the two phenotypes (and their underlying genotypes) can almost always be distinguished. In the albinism example, the A allele always allows some pigment formation, whereas the a allele always results in albinism when present in two copies. For this reason, discontinuous variation has been successfully used by geneticists to identify the underlying alleles and their role in cellular functions.

Geneticists distinguish two categories of discontinuous variation. In a natural population, the existence of two or more common discontinuous variants is called polymorphism (Greek; many forms). The various forms are called morphs. It is often found that different morphs are determined by different alleles of a single gene. Why do populations show genetic polymorphism? Special types of natural selection can explain a few cases, but, in other cases, the morphs seem to be selectively neutral.

Rare, exceptional discontinuous variants are called mutants, whereas the more common “normal” phenotype is called the wild type. Figure 1-12 shows an example of a mutant phenotype. Again, in many cases, the wild-type and mutant phenotypes are determined by different alleles of one gene. Both mutants and polymorphisms originally arise from rare changes in DNA (mutations), but somehow the mutant alleles of a polymorphism become common. These rare changes in DNA may be nucleotide-pair substitutions or small deletions or duplications. Such mutations change the amino acid composition of the protein. In the case of albinism, for example, the DNA of a gene that encodes an enzyme involved in melanin synthesis is changed, such that a crucial amino acid is replaced by another amino acid or lost, yielding a nonfunctioning enzyme. Mutants (such as those that produce albinism) can occur spontaneously in nature, or they can be produced by treatment with mutagenic chemicals or radiation.

Geneticists regularly induce mutations artificially to carry out genetic analysis because mutations that affect some specific biological function under study identify the various genes that interact in that function.