Latrille Thibault, Joseph Julien, Hartasánchez Diego A, Salamin Nicolas
Department of Computational Biology, Université de Lausanne, Lausanne, Switzerland.
Laboratoire de Biométrie et Biologie Evolutive, UMR5558, Université Lyon 1, Villeurbanne, France.
PLoS Genet. 2024 Dec 26;20(12):e1011536. doi: 10.1371/journal.pgen.1011536. eCollection 2024 Dec.
Mutations can be beneficial by bringing innovation to their bearer, allowing them to adapt to environmental change. These mutations are typically unpredictable since they respond to an unforeseen change in the environment. However, mutations can also be beneficial because they are simply restoring a state of higher fitness that was lost due to genetic drift in a stable environment. In contrast to adaptive mutations, these beneficial non-adaptive mutations can be predicted if the underlying fitness landscape is stable and known. The contribution of such non-adaptive mutations to molecular evolution has been widely neglected mainly because their detection is very challenging. We have here reconstructed protein-coding gene fitness landscapes shared between mammals, using mutation-selection models and a multi-species alignments across 87 mammals. These fitness landscapes have allowed us to predict the fitness effect of polymorphisms found in 28 mammalian populations. Using methods that quantify selection at the population level, we have confirmed that beneficial non-adaptive mutations are indeed positively selected in extant populations. Our work confirms that deleterious substitutions are accumulating in mammals and are being reverted, generating a balance in which genomes are damaged and restored simultaneously at different loci. We observe that beneficial non-adaptive mutations represent between 15% and 45% of all beneficial mutations in 24 of 28 populations analyzed, suggesting that a substantial part of ongoing positive selection is not driven solely by adaptation to environmental change in mammals.
突变可以通过为其携带者带来创新而具有益处，使其能够适应环境变化。这些突变通常是不可预测的，因为它们是对环境中不可预见的变化做出反应。然而，突变也可能是有益的，因为它们只是恢复了由于在稳定环境中的遗传漂变而丧失的更高适应性状态。与适应性突变不同，如果潜在的适应性景观是稳定且已知的，那么这些有益的非适应性突变是可以预测的。这种非适应性突变对分子进化的贡献一直被广泛忽视，主要是因为其检测极具挑战性。我们在此利用突变选择模型和87种哺乳动物的多物种比对，重建了哺乳动物之间共享的蛋白质编码基因适应性景观。这些适应性景观使我们能够预测在28个哺乳动物种群中发现的多态性的适应性效应。使用在种群水平上量化选择的方法，我们证实了有益的非适应性突变在现存种群中确实受到正选择。我们的工作证实，有害替代在哺乳动物中不断积累并正在被逆转，从而形成一种平衡，即基因组在不同位点同时受到破坏和修复。我们观察到，在分析的28个种群中的24个种群中，有益的非适应性突变占所有有益突变的15%至45%，这表明正在进行的正选择的很大一部分并非仅仅由哺乳动物对环境变化的适应所驱动。
