The effect of a mutation on the organism often depends on what other mutations are already present in its genome. Geneticists refer to such mutational interactions as epistasis. Pairwise epistatic effects have been recognized for over a century, and their evolutionary implications have received theoretical attention for nearly as long. However, pairwise epistatic interactions themselves can vary with genomic background. This is called higher-order epistasis, and its consequences for evolution are much less well understood. Here, we assess the influence that higher-order epistasis has on the topography of 16 published, biological fitness landscapes. We find that on average, their effects on fitness landscape declines with order, and suggest that notable exceptions to this trend may deserve experimental scrutiny. We conclude by highlighting opportunities for further theoretical and experimental work dissecting the influence that epistasis of all orders has on fitness landscape topography and on the efficiency of evolution by natural selection.

中文翻译：

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高阶上位性对生物适应性景观地形的影响

突变对生物体的影响通常取决于其基因组中已经存在的其他突变。遗传学家将这种突变相互作用称为上位性。一个多世纪以来，人们已经认识到成对的上位效应，并且它们的进化意义也受到了几乎同样长的理论关注。然而，成对的上位相互作用本身可能因基因组背景而异。这被称为高阶上位性，它对进化的影响却鲜为人知。在这里，我们评估了高阶上位性对 16 个已发表的生物适应性景观的地形的影响。我们发现，平均而言，它们对适应度景观的影响随着顺序而下降，并表明这一趋势的显着例外可能值得进行实验审查。