Systems Biology Program, Centre for Genomic Regulation, Barcelona Institute of Science and Technology, 08003 Barcelona, Spain; email:
Universitat Pompeu Fabra, 08003 Barcelona, Spain.
Annu Rev Genomics Hum Genet. 2019 Aug 31;20:433-460. doi: 10.1146/annurev-genom-083118-014857. Epub 2019 May 13.
The same mutation can have different effects in different individuals. One important reason for this is that the outcome of a mutation can depend on the genetic context in which it occurs. This dependency is known as epistasis. In recent years, there has been a concerted effort to quantify the extent of pairwise and higher-order genetic interactions between mutations through deep mutagenesis of proteins and RNAs. This research has revealed two major components of epistasis: nonspecific genetic interactions caused by nonlinearities in genotype-to-phenotype maps, and specific interactions between particular mutations. Here, we provide an overview of our current understanding of the mechanisms causing epistasis at the molecular level, the consequences of genetic interactions for evolution and genetic prediction, and the applications of epistasis for understanding biology and determining macromolecular structures.
相同的突变在不同个体中可能产生不同的影响。造成这种情况的一个重要原因是，突变的结果可能取决于其发生的遗传背景。这种依赖性被称为上位性。近年来，人们通过对蛋白质和 RNA 进行深度诱变，齐心协力地量化了突变之间的成对和更高阶遗传相互作用的程度。这项研究揭示了上位性的两个主要组成部分：由基因型到表型映射中的非线性引起的非特异性遗传相互作用，以及特定突变之间的特异性相互作用。在这里，我们概述了我们目前对分子水平上引起上位性的机制、遗传相互作用对进化和遗传预测的影响，以及上位性在理解生物学和确定大分子结构方面的应用的理解。
