Continuous Variation, Molecular Basis Of Allelic Variation

CONTINUOUS VARIATION A character showing continuous variation has an unbroken range of phenotypes in a population (see Figure 1-10b). Measurable characters such as height, weight, and skin or hair color are good examples of such variation. Intermediate phenotypes are

generally more common than extreme phenotypes. In some cases, all the variation is environmental and has no genetic basis, as in the case of the different languages spoken by different human groups. In other cases, such as that of the various shades of human eye color, the differences are caused by allelic variation in one or many genes. For most continuously variable characters, both genetic and environmental variation contribute to differences in phenotype. In continuous variation, there is no one-to-one correspondence of genotype and phenotype. For this reason, little is known about the types of genes underlying continuous variation, and only recently have techniques become available for identifying and characterizing them.

Continuous variation is encountered more commonly than discontinuous variation in everyday life. We can all identify examples of continuous variation, such as variation in size or shape, in plant or animal populations that we have observed—many examples exist in human populations. One area of genetics in which continuous variation is important is in plant and animal breeding. Many of the characters that are under selection in breeding programs, such as seed weight or milk production, arise from many gene differences interacting with environmental variation, and the phenotypes show continuous variation in populations. We shall return to the specialized techniques for analyzing continuous variation in Chapter 20, but for the greater part of the book, we shall be dealing with the genes underlying discontinuous variation.

Molecular basis of allelic variation

Consider the difference between the pigmented and the albino phenotypes in humans. The dark pigment

melanin has a complex structure that is the end product of a biochemical synthetic pathway. Each step in the pathway is a conversion of one molecule into another, with the progressive formation of melanin in a step-by-step manner. Each step is catalyzed by a separate enzyme protein encoded by a specific gene. Most cases of albinism result from changes in one of these enzymes—tyrosinase. The enzyme tyrosinase catalyzes the last step of the pathway, the conversion of tyrosine into melanin.

To perform this task, tyrosinase binds to its substrate, a molecule of tyrosine, and facilitates the molecular changes necessary to produce the pigment melanin. There is a specific “lock-and-key” fit between tyrosine and the active site of the enzyme. The active site is a pocket formed by several crucial amino acids in the polypeptide. If the DNA of the tyrosinase-encoding gene changes in such a way that one of these crucial amino acids is replaced by another amino acid or is lost, then there are several possible consequences. First, the enzyme might still be able to perform its functions but in a less efficient manner. Such a change may have only a small effect at the phenotypic level, so small as to be difficult to observe, but it might lead to a reduction in the amount of melanin formed and, consequently, a lighter skin coloration. Note that the protein is still present more or less intact, but its ability to convert tyrosine into melanin has been compromised. Second, the enzyme might be incapable of any function, in which case the mutational event in the DNA of the gene would have produced an albinism allele, referred to earlier as an a allele. Hence a person of genotype a/a is an albino.

The genotype A/a is interesting. It results in normal pigmentation because transcription of one copy of the wild type allele (A) can provide enough tyrosinase for synthesis of normal amounts of melanin. Genes are termed haplosufficient if roughly normal function is obtained when there is only a single copy of the normal gene. Wild-type alleles commonly appear to be haplosufficient, in part because small reductions in function are not vital to the organism. Alleles that fail to code for a functional protein are called null (“nothing”) alleles and are generally not expressed in combination with func-

tional alleles (in individuals of genotype A/a). The molecular basis of albinism is represented in Figure 1-13. Third, more rarely, the altered protein may perform its function more efficiently and thus be the basis for future evolution by natural selection.

The mutational site in the DNA can be of a number of types. The simplest and most common type is

nucleotide-pair substitution, which can lead to amino acid substitution or to premature stop codons. Small deletions and duplications also are common. Even a single base deletion or insertion produces widespread damage at the protein level; because mRNA is read from one end “in frame” in groups of three, a loss or gain of one nucleotide pair shifts the reading frame, and all the amino acids translationally downstream will be incorrect. Such mutations are called frameshift mutations.

At the protein level, mutation changes the amino acid composition of the protein. The most important

outcomes are change in protein shape and size. Such change in shape or size can result in an absence of biological function (which would be the basis of a null allele) or reduced function. More rarely, mutation can lead to new function of the protein product.