Center of Life Sciences, Skolkovo Institute of Science and Technology, Skolkovo, 143028, Russia.
Institute for Information Transmission Problems (Kharkevich Institute), Russian Academy of Sciences, Moscow, 127051, Russia.
Nat Commun. 2020 Sep 14;11(1):4603. doi: 10.1038/s41467-020-18366-z.
Amino acid propensities at a site change in the course of protein evolution. This may happen for two reasons. Changes may be triggered by substitutions at epistatically interacting sites elsewhere in the genome. Alternatively, they may arise due to environmental changes that are external to the genome. Here, we design a framework for distinguishing between these alternatives. Using analytical modelling and simulations, we show that they cause opposite dynamics of the fitness of the allele currently occupying the site: it tends to increase with the time since its origin due to epistasis ("entrenchment"), but to decrease due to random environmental fluctuations ("senescence"). By analysing the genomes of vertebrates and insects, we show that the amino acids originating at negatively selected sites experience strong entrenchment. By contrast, the amino acids originating at positively selected sites experience senescence. We propose that senescence of the current allele is a cause of adaptive evolution.
在蛋白质进化过程中，某个位置的氨基酸倾向性会发生变化。这可能有两个原因。变化可能是由基因组中其他上位相互作用位点的取代引发的。或者，它们可能是由于基因组外部的环境变化而产生的。在这里，我们设计了一个框架来区分这些替代方案。通过分析建模和模拟，我们表明它们导致了当前占据该位置的等位基因的适应性的相反动态：由于上位性（“根深蒂固”），它随着起源以来的时间而增加，但由于随机环境波动而减少（“衰老”）。通过分析脊椎动物和昆虫的基因组，我们发现负选择位点起源的氨基酸经历强烈的根深蒂固。相比之下，正选择位点起源的氨基酸经历衰老。我们提出，当前等位基因的衰老可能是适应性进化的原因。
