Department of Biology and Biochemistry, University of Bath, Bath, UK.
Mol Biol Evol. 2011 Aug;28(8):2339-49. doi: 10.1093/molbev/msr054. Epub 2011 Feb 24.
Changes in effective population size impinge on patterns of molecular evolution. Notably, slightly deleterious mutations are more likely to drift to fixation in smaller populations, which should typically also lead to an overall acceleration in the rates of evolution. This prediction has been validated empirically for several endosymbiont and island taxa. Here, we first show that rate accelerations are also evident in bacterial pathogens whose recent shifts in virulence make them prime candidates for reduced effective population size: Bacillus anthracis, Bordetella parapertussis, Mycobacterium leprae, Salmonella enterica typhi, Shigella spp., and Yersinia pestis. Using closely related genomes to analyze substitution rate dynamics across six phylogenetically independent bacterial clades, we demonstrate that relative rates of coding sequence evolution are biased according to gene functional category. Notably, genes that buffer against slightly deleterious mutations, such as chaperones, experience stronger rate accelerations than other functional classes at both nonsynonymous and synonymous sites. Although theory predicts altered evolutionary dynamics for buffer loci in the face of accumulating deleterious mutations, to observe even stronger rate accelerations is surprising. We suggest that buffer loci experience elevated substitution rates because the accumulation of deleterious mutations in the remainder of the genome favors compensatory substitutions in trans. Critically, the hyper-acceleration is evident across phylogenetically independent clades, supporting the hypothesis that reductions in effective population size predictably induce epistatic responses in genes that buffer against slightly deleterious mutations.
有效种群大小的变化影响着分子进化的模式。值得注意的是，稍微有害的突变在较小的种群中更有可能随机固定，这通常也会导致进化速度的整体加速。这一预测已经在几种内共生体和岛屿分类群中得到了经验验证。在这里，我们首先表明，在细菌病原体中也存在着速率加速的现象，这些病原体的毒力最近发生了变化，使其成为有效种群大小减少的主要候选者：炭疽杆菌、副百日咳博德特氏菌、麻风分枝杆菌、伤寒沙门氏菌、志贺氏菌和鼠疫耶尔森菌。我们使用密切相关的基因组来分析六个独立的细菌进化枝中的替代率动态，证明编码序列进化的相对速率根据基因功能类别而存在偏差。值得注意的是，缓冲轻微有害突变的基因，如伴侣蛋白，在非同义位点和同义位点的相对速率加速都比其他功能类别更强。尽管理论预测了在积累有害突变的情况下缓冲基因的进化动态会发生改变，但观察到甚至更强的速率加速是令人惊讶的。我们认为，缓冲基因经历了更高的替代率，因为基因组其余部分有害突变的积累有利于在转位中发生补偿性替换。关键的是，这种超加速在独立的进化枝中都很明显，支持了有效种群大小减少可预测地诱导缓冲稍微有害突变的基因的上位性反应的假说。
