McCandlish David M, Epstein Charles L, Plotkin Joshua B
Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania, 19104.
Evolution. 2014 May;68(5):1351-64. doi: 10.1111/evo.12350. Epub 2014 Mar 4.
Studies on the genetics of adaptation from new mutations typically neglect the possibility that a deleterious mutation might fix. Nonetheless, here we show that, in many regimes, the first mutation to fix is most often deleterious, even when fitness is expected to increase in the long term. In particular, we prove that this phenomenon occurs under weak mutation for any house-of-cards model with an equilibrium distribution. We find that the same qualitative results hold under Fisher's geometric model. We also provide a simple intuition for the surprising prevalence of unconditionally deleterious substitutions during early adaptation. Importantly, the phenomenon we describe occurs on fitness landscapes without any local maxima and is therefore distinct from "valley crossing." Our results imply that the common practice of ignoring deleterious substitutions leads to qualitatively incorrect predictions in many regimes. Our results also have implications for the substitution process at equilibrium and for the response to a sudden decrease in population size.
关于新突变适应遗传学的研究通常忽略了有害突变可能固定下来的可能性。然而，我们在此表明，在许多情况下，即使从长远来看适应度预期会增加，第一个固定下来的突变往往是有害的。特别是，我们证明了对于任何具有平衡分布的纸牌屋模型，在弱突变情况下都会出现这种现象。我们发现在费希尔几何模型下也有相同的定性结果。我们还为早期适应过程中无条件有害替代的惊人普遍性提供了一个简单的直观解释。重要的是，我们所描述的现象发生在没有任何局部最大值的适应度景观上，因此不同于“跨越山谷”。我们的结果表明，在许多情况下，忽略有害替代的常见做法会导致定性错误的预测。我们的结果还对平衡状态下的替代过程以及对种群大小突然减少的反应有影响。
