Molecular and Computational Biology Section, Department of Biological Sciences, University of Southern California, Los Angeles, CA, 90089-2910, USA.
Nat Commun. 2018 Sep 17;9(1):3548. doi: 10.1038/s41467-018-06023-5.
Genetic interactions between mutations and standing polymorphisms can cause mutations to show distinct phenotypic effects in different individuals. To characterize the genetic architecture of these so-called background effects, we genotype 1411 wild-type and mutant yeast cross progeny and measure their growth in 10 environments. Using these data, we map 1086 interactions between segregating loci and 7 different gene knockouts. Each knockout exhibits between 73 and 543 interactions, with 89% of all interactions involving higher-order epistasis between a knockout and multiple loci. Identified loci interact with as few as one knockout and as many as all seven knockouts. In mutants, loci interacting with fewer and more knockouts tend to show enhanced and reduced phenotypic effects, respectively. Cross-environment analysis reveals that most interactions between the knockouts and segregating loci also involve the environment. These results illustrate the complicated interactions between mutations, standing polymorphisms, and the environment that cause background effects.
遗传突变与等位基因多态性之间的相互作用可能导致突变在不同个体中表现出不同的表型效应。为了描述这些所谓的背景效应的遗传结构，我们对 1411 个野生型和突变酵母杂交后代进行了基因型分析，并在 10 种环境中测量了它们的生长情况。利用这些数据，我们绘制了 1086 个分离位点与 7 种不同基因敲除之间的相互作用图谱。每个敲除体都表现出 73 到 543 个相互作用，其中 89%的相互作用涉及敲除体与多个位点之间的高阶上位性。鉴定出的位点与少至一个敲除体和多达七个敲除体相互作用。在突变体中，与较少和较多敲除体相互作用的位点分别倾向于表现出增强和降低的表型效应。跨环境分析表明，敲除体与分离位点之间的大多数相互作用也涉及环境。这些结果说明了突变、等位基因多态性和环境之间复杂的相互作用，导致了背景效应。
