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Modern Genetic Analysis Chapter 6. Gene Interaction
From Genes to Phenotypes

At one level, geneticists tend to think of genes in isolation. Every time we do a cross of a red-eyed (wild-type) strain of Drosophila with a white-eyed mutant strain, each parent and each offspring contain some 20,000 or so genes. Nonetheless, in such a cross, we would take note only of the one segregating genetic difference that we care aboutthe eye color of each fly. In reality, genes don't act in isolation. The proteins and RNAs they encode contribute to specific cellular pathways that also receive input from the products of many other genes. Furthermore, expression of a single gene is dependent on many factors, including the specific genetic backgrounds of the flies and a range of environmental conditionstemperature, nutritional conditions, population density, and so on. (Such dependence of gene expression on environmental factors was discussed in Chapter 1 in the section on the norm of reaction.)

Gene action is a term that covers a very complex set of events, and there is probably no case where we understand all the events that transpire from the level of expression of a single gene to the level of an organism's phenotype. In this chapter, we will discuss some of the methods geneticists use to unravel the mechanistic strands that connect gene to final phenotype.

We can start by making a couple of generalizations about the complexity of gene action.

1. There is a one-to-many relationship of genes to phenotypes.

This relationship is called pleiotropy. Pleiotropy is inferred from the observation that mutations selected for their effect on one specific character are often found to affect other characters of the organism. This might mean that there are related physiological pathways contributing to a similar phenotype in several tissues. For example, the white eye-color mutation in Drosophila results in lack of pigmentation not only in compound eyes but also in ocelli (simple eyes), sheaths of tissue surrounding the male gonad, and the Malpighian tubules (the fly's kidneys). In all these tissues, pigment formation requires the uptake of pigment precursors by the cells. The white allele causes a defect in this uptake, thereby blocking pigment formation in all these tissues.

Often, pleiotropy involves multiple events that are not obviously physiologically related. For example, the dominant Drosophila mutation Dichaete causes the wings to be held out laterally but also removes certain hairs on the back of the fly; furthermore, the mutation is inviable when homozygous. This example shows a real limitation in the way dominant and recessive mutations are named. The reality is that a single mutation can be both dominant and recessive, depending on which aspect of its pleiotropic phenotype is under consideration. In general, genetic terminology is not up to the task of representing this level of pleiotropy and complexity in one symbol, and as we will discuss below, there is a certain arbitrary or historical aspect as to how we name alleles. In this chapter, we will consider some of the variations on the general theme of dominance/recessiveness and some of the traditional ways that alleles are named.

2. There is a one-to-many relationship of phenotypes to genes.

This idea, the converse of the first, is based on the observation that many different genes can affect a single phenotype. This is easy to understand in terms of a character such as eye color, in which there are complex metabolic pathways with numerous enzymatic steps, each encoded by one or more gene products. Thus, in Drosophila, there are estimated to be 100 or more genes that contribute to pigmentation of the compound eye of the fly. For more complex processes, such as the development of the structure of the compound eye, there are probably many hundreds that contribute to the process.

One goal of genetic analysis is to identify all the genes that affect a specific phenotype and to understand their genetic, cellular, developmental, and molecular roles. To do this, we need ways of sorting mutations and genes. In the first section of this chapter, we will be discussing how we can use genetic analysis to determine if two mutants are caused by mutational hits in the same gene (that is, they are alleles) or in different genes. Later in the chapter, we will consider how genetic analysis can be used to make inferences about gene interactions in developmental and biochemical pathways.

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