Evolution of Genetic Architecture

基因的作用可能因其他基因座上存在哪些基因而有所不同。这种现象被称为上位。上位相互作用对基因效应的集体效应被称为遗传背景效应。微进化和物种形成的一个重要问题是，这种遗传背景本身是否会进化，从而改变其中基因的影响。一种特定的基因变异是否受到青睐取决于它在哪种遗传背景中表达。在之前的研究中，我们发现在大（LG/J）和小（SM/J）小鼠品系杂交中，影响成年鼠体型的基因存在显著的上位性。因此，一个基因是否使个体大于平均水平取决于存在哪些其他基因（遗传背景）。我们还发现了颌骨特征的差异效应，这意味着特定基因是否影响整体颌骨大小和局部颌骨特征取决于遗传或环境背景。上位性相互作用的存在促进了遗传背景的进化。在提议的工作中，我们将在两个实验中检查遗传背景进化的机会。首先，我们将测试影响下颌大小和形状的特定位点及其不同遗传背景之间的遗传相互作用，以200个独立的全同胞家庭为代表。这将使我们能够确定对颌骨特征集的差异影响是由于遗传还是环境背景。如果差异效应是由遗传背景造成的，那么单个基因位点的多重效应（多效性）就有可能进化。其次，我们将从大鼠和小鼠的杂交中制备一系列重复的重组自交系。随着上位性，这些重组自交系有望进化出不同的遗传背景。这将通过将几个自交系的雄性交配到每个大x小重组自交系中来测试。如果这些“迁移”雄性的影响取决于它与哪一种重组自交系交配，那么重组自交系的遗传背景已经进化。根据遗传背景的不同，进入每个菌株的突变或迁移的影响会有所不同。在种群分化和/或物种形成过程中，遗传背景的演变可能导致同一基因（通过迁移或突变引入）在不同的亚种群中具有不同的作用，从而导致种群的进化分化甚至生殖隔离，即使在相似的选择压力下也是如此。

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.