Laboratory of Genetics, Wageningen University, Wageningen, The Netherlands.
Proc Biol Sci. 2011 Dec 22;278(1725):3617-24. doi: 10.1098/rspb.2011.1537. Epub 2011 Oct 5.
Since Bateson's discovery that genes can suppress the phenotypic effects of other genes, gene interactions-called epistasis-have been the topic of a vast research effort. Systems and developmental biologists study epistasis to understand the genotype-phenotype map, whereas evolutionary biologists recognize the fundamental importance of epistasis for evolution. Depending on its form, epistasis may lead to divergence and speciation, provide evolutionary benefits to sex and affect the robustness and evolvability of organisms. That epistasis can itself be shaped by evolution has only recently been realized. Here, we review the empirical pattern of epistasis, and some of the factors that may affect the form and extent of epistasis. Based on their divergent consequences, we distinguish between interactions with or without mean effect, and those affecting the magnitude of fitness effects or their sign. Empirical work has begun to quantify epistasis in multiple dimensions in the context of metabolic and fitness landscape models. We discuss possible proximate causes (such as protein function and metabolic networks) and ultimate factors (including mutation, recombination, and the importance of natural selection and genetic drift). We conclude that, in general, pleiotropy is an important prerequisite for epistasis, and that epistasis may evolve as an adaptive or intrinsic consequence of changes in genetic robustness and evolvability.
自贝特森发现基因可以抑制其他基因的表型效应以来，基因相互作用——称为上位性——一直是大量研究的主题。系统生物学家和发育生物学家研究上位性以了解基因型-表型图谱，而进化生物学家则认识到上位性对进化的基本重要性。根据其形式，上位性可能导致分歧和物种形成，为性提供进化优势，并影响生物体的稳健性和可进化性。最近才意识到，上位性本身可以被进化所塑造。在这里，我们回顾了上位性的经验模式，以及可能影响上位性形式和程度的一些因素。根据它们不同的后果，我们将具有或不具有平均效应的相互作用以及那些影响适应度效应幅度或其符号的相互作用区分开来。在代谢和适应度景观模型的背景下，实证工作已经开始在多个维度上量化上位性。我们讨论了可能的近似原因（如蛋白质功能和代谢网络）和最终因素（包括突变、重组以及自然选择和遗传漂变的重要性）。我们的结论是，一般来说，多效性是上位性的一个重要前提，并且上位性可能作为遗传稳健性和可进化性变化的适应性或内在结果而进化。
