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Modern Genetic Analysis Chapter 1. Genetics and the Organism
Genetics begins with Variation

Mendel's concept of the gene was based on the analysis of hereditary variantsorganisms that show identifiable and persistent differences for specific characters. He was the first to establish rules for the genetic analysis of such distinct variants. This was an important step because questions about variation dominate the field of heredity, and most genetic analysis begins with variants of some type. Two central questions of heredity focus on variation. What determines the fundamental characteristics of different species (that is, what causes variation between species)? Secondly, what determines variation within a species? Genes are key components of the answers to both questions. A species is unique because of the unique set of genes that it owns. Even though it is now known that there is considerable overlap in the genomes of different species, nevertheless the genome of each species is unique. One of the goals of genetics is to understand precisely how genes do shape the characteristics of a species. This goal has been made considerably more attainable through advances in understanding the molecular nature of genes and how they work.

Variation within a species is a common everyday observation. For example, we use such variation to identify individual human beings and to distinguish our pets from those of others. However, variation within a species has two possible causes, variation of genes and variation of the environment; so in any particular case experimental analysis is needed to measure the relative components of variation. How is it possible for there to be variation of the gene set that is characteristic of a species? That is, if all members of a species have the same gene set, how can there be genetic variation? The answer is that genes come in different forms called alleles. For example, there may be a single gene for flower color, but several alleles, each producing a flower of a different color. In a population there can be from one to many different alleles of one gene, but since organisms carry only one or two chromosome sets per cell, any individual can carry only one or two alleles of a gene. The alleles of a given gene will always be found at the same chromosomal position. Alleles of a gene represent different levels of activity, new activity, or no activity of that gene. An allele is produced by mutation, involving changes of one or more nucleotide pairs in its DNA. This allelic variation is the basis for hereditary variation.

It is important to understand the types of variation found within a species. One useful classification system divides variation into discontinuous and continuous variation. In discontinuous variation a character is found in a population in two or more distinct and separate forms. The expressed form of a character is called the phenotype. For example, one of the characters Mendel studied was flower color in peas, of which there were two distinct phenotypes, purple and white. These are caused by two different alleles of a single gene for color: the purple allele stands for the ability to make purple pigment, and the white allele stands for a lack of ability to form purple pigment, resulting in whiteness. Indeed in general it is often found that contrasting phenotypes are determined by different alleles of a single gene, as Mendel found for petal color. The specific set of alleles carried by an individual is called the genotype, which is the hereditary underpinning of the phenotype. However, the DNA of a gene obviously cannot produce a phenotype unaided; DNA in a test tube is inert. To have any influence on phenotype, the DNA of an allele of a single gene must act in a cell in concert with other genes and with the environment. The general range of phenotypic impacts of a genotype under different genetic and environmental backgrounds is called its norm of reaction (Figure 1-12). In most cases of discontinuous variation that can be shown to be based on alleles of a single gene, the norms of reaction of the different alleles are generally nonoverlapping. This results in a predictable one-to-one relationship between genotype and phenotype in most environments and genetic backgrounds (Figure 1-13). In the above example from Mendel's work, the purple allele will virtually always result in purple petals, whereas the white allele always produces white. For this reason discontinuous variation has been successfully used by geneticists to identify the underlying alleles and their cellular functions. Indeed allele-based discontinuous variants are the starting point of most genetic research.

In a natural population, the existence of two or more common alternative phenotypes is called polymorphism (Greek: "many forms"); an example is shown in Figure 1-14a. The various phenotypes are sometimes called morphs. Often such 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.

Rare, exceptional discontinuous variant phenotypes are designated 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 alleles of one gene. Mutants can occur spontaneously in nature, or they can be obtained after treatment of laboratory populations with mutagenic chemicals or radiation.

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Discrete phenotypic forms of one character are often found to be determined by alleles of a single gene.

Continuous variation of a character shows an unbroken range of phenotypes in the population. Metric characters such as height, weight, and color intensity provide good examples of continuous variation. Intermediate phenotypes are generally more common than extreme phenotypes, and when phenotypic frequencies are plotted as a graph, a bell-shaped phenotypic distribution is observed. (Continuous variation is represented and contrasted with discontinuous variation in a natural population in Figure 1-15.) In some continuous 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 a small or a large number of genes. In most cases there is both genetic and environmental variation. In continuous distributions the norms of reactions of individual genotypes are complex and there is no one-to-one correspondence of genotype and phenotype (Figure 1-16). For this reason little is known about the types of genes underlying continuous variation. However, recently new and more powerful molecular techniques have become available for identifying and characterizing them.

Continuous variation is encountered more commonly than discontinuous variation in everyday life. We can all point to cases of continuous variation we have observed in plant or animal populations (fruit size, crop yield, etc.); human populations provide many examples as well. 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, show continuous variation in populations. Animals or plants from one extreme end of the range are chosen and selectively bred. Before undertaking such selection, it is necessary to perform analyses to estimate the sizes of the genetic and environmental components of the variation.

Some discontinuous variant phenotypes have a complex inheritance that resembles that of continuous variation. Examples in human populations are heart disease, diabetes, cleft lip and palate, and pyloric stenosis (blocked exit from the stomach). The risk of a child's being born with these conditions is higher in families in which relatives are affected; hence, there seems to be a genetic component, but the inheritance does not follow the simple allelic pattern shown by Mendel. It is believed that these phenotypes are based on multiple gene and environmental interactions, with some type of physiological threshold beyond which the variant phenotype is expressed.

We return to quantitative inheritance in Chapters 12 and 18, but for the greater part of the book we will be dealing with the genes underlying simple discontinuous variation determined by alleles of single genes.

© 1999 by W. H. Freeman and Company. All rights reserved.