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Griffiths AJF, Miller JH, Suzuki DT, et al. An Introduction to Genetic Analysis. 7th edition. New York: W. H. Freeman; 2000.

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An Introduction to Genetic Analysis. 7th edition.

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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 one chromosomal position. 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 1-12). Allelic variation contributes to both.

Figure 1-12. Discontinuous and continuous variation in natural populations.

Figure 1-12

Discontinuous and continuous variation in natural populations. In populations showing discontinuous variation for a particular character, each member possesses one of several discrete alternatives. For example, in the left-hand panel, a population of (more...)

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. 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 subtropical ancestry. Although always rare, albinos are found in all races; they have a totally pigmentless skin and hair (Figure 1-13). The difference between pigmented and unpigmented is caused by two alleles of a gene taking part in melanin synthesis. The alleles of a gene are conventionally designated by letters. The allele that codes for the ability to make melanin is called A and the allele that codes for the inability to make melanin (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 they are a pair). The phenotype of A/A is pigmented, a/a is albino, and 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).

Figure 1-13. An albino.

Figure 1-13

An albino. The phenotype is caused by two doses of a recessive allele – a / a. The dominant allele A determines one step in the chemical synthesis of the dark pigment melanin in the cells of skin, hair, and eye retinas. In a / a individuals, this (more...)

Although allelic differences cause phenotypic differences such as pigmented and albino, this does not mean that only one gene affects skin color. It is known that there are several. However, the difference between pigmented, of whatever shade, and albino is caused by the difference at one gene; the state of all the other pigment genes is irrelevant.

In 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 white allele always results in albinism when homozygous. 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 on the basis of simple allelic differences. In a natural population, the existence of two or more common discontinuous variants is called polymorphism (Greek; many forms), and an example is shown in Figure 1-14a. The various forms are called morphs. It is often found that morphs are determined by the 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.

Figure 1-14. A dimorphism.

Figure 1-14

A dimorphism. (a) The fruits of two different forms of Plectritis congesta, the sea blush. Any one plant has either all wingless or all winged fruits. In every other way, the plants are identical. (b) A Drosophila mutant with abnormal wings and a normal (more...)

Rare, exceptional discontinuous variants are called mutants, whereas the more common “normal” companion phenotype is called the wild type. Figure 1-14b shows an example of a mutant phenotype. Again, in many cases, the wild-type and mutant phenotypes are determined by the alleles of one gene. Mutants can occur spontaneously in nature (for example, albinos) or they can be obtained after treatment with mutagenic chemicals or radiations. 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. Note that polymorphisms originally arise as mutations, but somehow the mutant allele becomes common.


In many cases, an allelic difference at a single gene may result in discrete phenotypic forms that make it easy to study the gene and its associated biological function.

Continuous variation of a character shows an unbroken range of phenotypes in the population (see Figure 1-12). Measurable characters such as height, weight, and color intensity are good examples of such variation. Intermediate phenotypes are generally more common than extreme phenotypes and, when phenotypic frequencies are plotted as a graph, a bell-shaped distribution is observed. In some such distributions, all the variation is environmental and has no genetic basis at all. In other cases, there is a genetic component caused by allelic variation of one or many genes. In most cases, there is both genetic and environmental variation. In continuous distributions, 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 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, have complex determination, and the phenotypes show continuous variation in populations. Animals or plants from one extreme end of the range are chosen and selectively bred. Before such selection is undertaken, the sizes of the genetic and environmental components of the variation must be known. We shall return to these specialized techniques 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.

Image ch1e5.jpg

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 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. Alleles are termed haplosufficient if roughly normal function is obtained when there is only a single copy of the normal gene. 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 functional alleles (in individuals of genotype A/a). The molecular basis of albinism is represented in Figure 1-15.

Figure 1-15. Molecular basis of albinism.

Figure 1-15

Molecular basis of albinism. Expression in cells containing 2, 1, and 0 copies of the normal tyrosinase allele on chromosome 14. Melanocytes are specialized melanin-producing cells.

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 duplication 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 shape and size. Such change in shape or size can result in no 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.


New alleles formed by mutation can result in no function, less function, or new function at the protein level.

By agreement with the publisher, this book is accessible by the search feature, but cannot be browsed.

Copyright © 2000, W. H. Freeman and Company.
Bookshelf ID: NBK22007


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