Good Benjamin H, Desai Michael M
Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, Massachusetts 02138.
Department of Physics, Harvard University, Cambridge, Massachusetts 02138.
Genetics. 2016 Nov;204(3):1249-1266. doi: 10.1534/genetics.116.193565. Epub 2016 Sep 19.
Mutator and antimutator alleles often arise and spread in both natural microbial populations and laboratory evolution experiments. The evolutionary dynamics of these mutation rate modifiers are determined by indirect selection on linked beneficial and deleterious mutations. These indirect selection pressures have been the focus of much earlier theoretical and empirical work, but we still have a limited analytical understanding of how the interplay between hitchhiking and deleterious load influences the fates of modifier alleles. Our understanding is particularly limited when clonal interference is common, which is the regime of primary interest in laboratory microbial evolution experiments. Here, we calculate the fixation probability of a mutator or antimutator allele in a rapidly adapting asexual population, and we show how this quantity depends on the population size, the beneficial and deleterious mutation rates, and the strength of a typical driver mutation. In the absence of deleterious mutations, we find that clonal interference enhances the fixation probability of mutators, even as they provide a diminishing benefit to the overall rate of adaptation. When deleterious mutations are included, natural selection pushes the population toward a stable mutation rate that can be suboptimal for the adaptation of the population as a whole. The approach to this stable mutation rate is not necessarily monotonic: even in the absence of epistasis, selection can favor mutator and antimutator alleles that "overshoot" the stable mutation rate by substantial amounts.
突变体和抗突变体等位基因经常在自然微生物群体和实验室进化实验中出现并传播。这些突变率修饰因子的进化动态由对连锁的有益和有害突变的间接选择决定。这些间接选择压力一直是早期许多理论和实证研究的重点，但我们对搭便车和有害负荷之间的相互作用如何影响修饰因子等位基因的命运仍缺乏深入的分析理解。当克隆干扰普遍存在时，我们的理解尤其有限，而克隆干扰正是实验室微生物进化实验中主要关注的情况。在这里，我们计算了在快速适应的无性群体中突变体或抗突变体等位基因的固定概率，并展示了这个量如何依赖于群体大小、有益和有害突变率以及典型驱动突变的强度。在没有有害突变的情况下，我们发现克隆干扰提高了突变体的固定概率，即使它们对整体适应率的益处逐渐减少。当纳入有害突变时，自然选择会将群体推向一个稳定的突变率，而这个突变率对整个群体的适应来说可能并非最优。达到这个稳定突变率的过程不一定是单调的：即使在没有上位性的情况下，选择也可能青睐那些大幅“超过”稳定突变率的突变体和抗突变体等位基因。
