Lewis-Sigler Institute for Integrative Genomics and Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA.
Nature. 2013 Aug 29;500(7464):571-4. doi: 10.1038/nature12344. Epub 2013 Jul 21.
The dynamics of adaptation determine which mutations fix in a population, and hence how reproducible evolution will be. This is central to understanding the spectra of mutations recovered in the evolution of antibiotic resistance, the response of pathogens to immune selection, and the dynamics of cancer progression. In laboratory evolution experiments, demonstrably beneficial mutations are found repeatedly, but are often accompanied by other mutations with no obvious benefit. Here we use whole-genome whole-population sequencing to examine the dynamics of genome sequence evolution at high temporal resolution in 40 replicate Saccharomyces cerevisiae populations growing in rich medium for 1,000 generations. We find pervasive genetic hitchhiking: multiple mutations arise and move synchronously through the population as mutational 'cohorts'. Multiple clonal cohorts are often present simultaneously, competing with each other in the same population. Our results show that patterns of sequence evolution are driven by a balance between these chance effects of hitchhiking and interference, which increase stochastic variation in evolutionary outcomes, and the deterministic action of selection on individual mutations, which favours parallel evolutionary solutions in replicate populations.
适应的动态决定了哪些突变在种群中固定,因此也决定了可重复性进化的程度。这对于理解抗生素耐药性进化中恢复的突变谱、病原体对免疫选择的反应以及癌症进展的动态至关重要。在实验室进化实验中,可明显证明有益的突变被反复发现,但通常伴随着其他没有明显益处的突变。在这里,我们使用全基因组全种群测序技术,以高时间分辨率在富含营养的培养基中生长 1000 代的 40 个重复酿酒酵母种群中研究了基因组序列进化的动态。我们发现普遍存在遗传连锁:多个突变作为突变“群体”同时出现并在种群中同步移动。多个克隆群体经常同时存在,在同一群体中相互竞争。我们的研究结果表明,序列进化的模式是由连锁和干涉的随机效应与选择对单个突变的确定性作用之间的平衡所驱动的,这种平衡增加了进化结果的随机变异,而选择有利于在重复种群中出现平行的进化解决方案。