Unité Mixte de Recherche 1137 (IAME-INSERM), Université Paris Diderot, 75018, Paris, France.
Department of Life Sciences, Imperial College London, London, SW7 2AZ, UK.
Nat Commun. 2019 Jul 15;10(1):3114. doi: 10.1038/s41467-019-11217-6.
Mutators represent a successful strategy in rapidly adapting asexual populations, but theory predicts their eventual extinction due to their unsustainably large deleterious load. While antimutator invasions have been documented experimentally, important discrepancies among studies remain currently unexplained. Here we show that a largely neglected factor, the mutational idiosyncrasy displayed by different mutators, can play a major role in this process. Analysing phylogenetically diverse bacteria, we find marked and systematic differences in the protein-disruptive effects of mutations caused by different mutators in species with different GC compositions. Computer simulations show that these differences can account for order-of-magnitude changes in antimutator fitness for a realistic range of parameters. Overall, our results suggest that antimutator dynamics may be highly dependent on the specific genetic, ecological and evolutionary history of a given population. This context-dependency further complicates our understanding of mutators in clinical settings, as well as their role in shaping bacterial genome size and composition.
突变体代表了一种在快速适应无性种群方面取得成功的策略，但理论预测它们最终会因不可持续的大量有害负荷而灭绝。虽然已经在实验中记录了抗突变体的入侵，但目前仍有一些重要的差异无法解释。在这里，我们表明，一个被广泛忽视的因素，即不同突变体所表现出的突变体独特性，可以在这个过程中发挥主要作用。通过分析系统发育上多样化的细菌，我们发现不同 GC 组成的物种中，不同突变体引起的突变对蛋白质的破坏作用存在显著且系统的差异。计算机模拟表明，这些差异可以解释在现实参数范围内，抗突变体适应性的数量级变化。总的来说，我们的研究结果表明，抗突变体的动态可能高度依赖于特定种群的具体遗传、生态和进化历史。这种背景依赖性进一步增加了我们对临床环境中突变体的理解，以及它们在塑造细菌基因组大小和组成方面的作用。
