3.4 Polygenic Inheritance

So far, our analysis in this book has focused on single-gene differences, with the use of sharply contrasting phenotypes such as red versus white petals, smooth versus wrinkled seeds, and long- versus vestigial-winged Drosophila. However, much of the variation found in nature is continuous, in which a phenotype can take any measurable value between two extremes. Height, weight, and color intensity are examples of such metric, or quantitative, phenotypes. Typically, when the metric value is plotted against frequency in a natural population, the distribution curve is shaped like a bell (Figure 3-14). The bell shape is due to the fact that average values in the middle are the most common, whereas extreme values are rare. At first it is difficult to see how continuous distributions can be influenced by genes inherited in a Mendelian manner; after all Mendelian analysis is facilitated by using clearly distinguishable categories. However, we shall see in this section that the independent assortment of several-to-many heterozygous genes affecting a continuous trait can produce a bell curve.

Figure 3-14: Continuous variation in a natural population
Figure 3-14: In a population, a metric character such as color intensity can take on many values. Hence, the distribution is in the form of a smooth curve, with the most common values representing the high point of the curve. If the curve is symmetrical, it is bell shaped, as shown.

Of course many cases of continuous variation have a purely environmental basis, little affected by genetics. For example, a population of genetically homozygous plants grown in a plot of ground often show a bell-shaped curve for height, with the smaller plants around the edges of the plot and the larger plants in the middle. This variation can be explained only by environmental factors such as moisture and amount of fertilizer applied. However, many cases of continuous variation do have a genetic basis. Human skin color is an example: all degrees of skin darkness can be observed in populations from different parts of the world, and this variation clearly has a genetic component. In such cases, from several to many alleles interact with a more or less additive effect. The interacting genes underlying hereditary continuous variation are called polygenes or quantitative trait loci (QTLs). (The term quantitative trait locus needs some definition: quantitative is more or less synonymous with continuous; trait is more or less synonymous with character or property; locus, which literally means place on a chromosome, is more or less synonymous with gene.) The polygenes, or QTLs, for the same trait are distributed throughout the genome; in many cases, they are on different chromosomes and show independent assortment.

Let’s see how the inheritance of several heterozygous polygenes (even as few as two) can generate a bell-shaped distribution curve. We can consider a simple model that was originally used to explain continuous variation in the degree of redness in wheat seeds. The work was done by Hermann Nilsson-Ehle in the early twentieth century. We will assume two independently assorting gene pairs R1/r1 and R2 /r2. Both R1 and R2 contribute to wheat-seed redness. Each “dose” of an R allele of either gene is additive, meaning that it increases the degree of redness proportionately. An illustrative cross is a self of a dihybrid R1/r1 ; R2 /r2. Both male and female gametes will show the genotypic proportions as follows:

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Overall, in this gamete population, one-fourth have two doses, one-half have one dose, and one-fourth have zero doses. The union of male and female gametes both showing this array of R doses is illustrated in Figure 3-15. The number of doses in the progeny ranges from four (R1/R1; R2/R2) down to zero (r1/r2; r2/r2), with all values between.

Figure 3-15: Polygenes in progeny of a dihybrid self
Figure 3-15: The progeny of a dihybrid self for two polygenes can be expressed as numbers of additive allelic “doses.”

The proportions in the grid of Figure 3-15 can be drawn as a histogram, as shown in Figure 3-16. The shape of the histogram can be thought of as a scaffold that could be the underlying basis for a bell-shaped distribution curve. When this analysis of redness in wheat seeds was originally done, variation was found within the classes that allegedly represented one polygene “dose” level. Presumably, this variation within a class is the result of environmental differences. Hence, the environment can be seen to contribute in a way that rounds off the sharp shoulders of the histogram bars, resulting in a smooth bell-shaped curve (the red line in the histogram). If the number of polygenes is increased, the histogram more closely approximates a smooth continuous distribution. For example, for a characteristic determined by three polygenes, the histogram is as shown in Figure 3-17.

Figure 3-17: Histogram of polygenes from a trihybrid self
Figure 3-17: The progeny of a polygene trihybrid can be graphed as a frequency histogram of contributing polygenic alleles (“doses”).
Figure 3-16: Histogram of polygenes from a dihybrid self
Figure 3-16: The progeny shown in Figure 3-15 can be represented as a frequency histogram of contributing polygenic alleles (“doses”).

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In our illustration, we used a dihybrid self to show how the histogram is produced. But how is our example relevant to what is going on in natural populations? After all, not all crosses could be of this type. Nevertheless, if the alleles at each gene pair are approximately equal in frequency in the population (for example, R1 is about as common as r1), then the dihybrid cross can be said to represent an average cross for a population in which two polygenes are segregating.

Identifying polygenes and understanding how they act and interact are important challenges for geneticists in the twenty-first century. Identifying polygenes will be especially important in medicine. Many common human diseases such as atherosclerosis (hardening of the arteries) and hypertension (high blood pressure) are thought to have a polygenic component. If so, a full understanding of these conditions, which affect large proportions of human populations, requires an understanding of these polygenes, their inheritance, and their function. Today, several molecular approaches can be applied to the job of finding polygenes, and we will consider some in subsequent chapters. Note that polygenes are not considered a special functional class of genes. They are identified as a group only in the sense that they have alleles that contribute to continuous variation.

KEY CONCEPT

Variation and assortment of polygenes can contribute to continuous variation in a population.