Evolution of Genetic Architecture

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Cheverud 9726433 The effects of genes may differ depending on which genes are present at other loci. This phenomenon is known as epistasis. The collective effect of epistatic interactions on gene effects is referred to as the effect of genetic background. An important problem in microevolution and speciation revolves around whether this genetic background itself evolves, thereby changing the effects of the genes placed in them. Whether a particular genetic variant is favored or not depends on which genetic background it is expressed in. In previous studies, we have found substantial epistasis among genes affecting adult body size in the cross between Large (LG/J) and Small (SM/J) mouse strains. Thus, whether a gene makes an individual larger than average depends on which other genes are present (the genetic background). We have also found differential effects for jaw characters, meaning that whether a specific gene affects both overall jaw size and local jaw traits depends on either the genetic or environmental background. The presence of epistatic interactions facilitates the evolution of the genetic background. In the proposed work, we will examine the opportunity for genetic background evolution in two experiments. First, we will test for genetic interactions between specific loci affecting the size and shape of the jaw and their varying genetic backgrounds, represented by 200 independent full-sib families. This will allow us to determine whether differential effects on sets of jaw characters are due to genetic or environmental backgrounds. If the differential effects are due to genetic background, then it is possible for the multiple effects of single gene loci (pleiotropy) to evolve. Second, we will prepare a series of replicate recombinant inbred lines from the cross of Large and Small mouse strains. With epistasis, it is expected that these recombinant inbred lines will evolve different genetic backgrounds. This will be tested by mating males from sever al inbred strains into each of the Large x Small recombinant inbred lines. If the effect of these "migrant" males differs depending on which recombinant inbred strain it is mated to, the genetic background of the recombinant inbred strains has evolved. The effect of mutations, or migrants, entering each strain will vary, depending on the genetic background. The evolution of genetic background during population divergence and/or speciation can result in the same gene (introduced by migration or mutation) having a different effect in different subpopulations resulting in the evolutionary divergence and even reproductive isolation of the populations, even under similar selection pressures.