High mutation rates limit evolutionary adaptation in Escherichia coli

Mutation is fundamental to evolution, because it generates the genetic variation on which selection can act. In nature, genetic changes often increase the mutation rate in systems that range from viruses and bacteria to human tumors. Such an increase promotes the accumulation of frequent deleterious or neutral alleles, but it can also increase the chances that a population acquires rare beneficial alleles. Here, we study how up to 100-fold increases in Escherichia coli’s genomic mutation rate affect adaptive evolution. To do so, we evolved multiple replicate populations of asexual E. coli strains engineered to have four different mutation rates for 3000 generations in the laboratory. We measured the ability of evolved populations to grow in their original environment and in more than 90 novel chemical environments. In addition, we subjected the populations to whole genome population sequencing. Although populations with higher mutation rates accumulated greater genetic diversity, this d...突变是演化的核心基础，因其产生了选择作用所依赖的遗传变异。在自然界中，从病毒、细菌到人类肿瘤的各类生物系统中，遗传改变往往会提升突变率。这类突变率的提升会促进高频有害或中性等位基因的积累，但同时也会增加种群获得稀有有益等位基因的概率。本研究聚焦于大肠杆菌（Escherichia coli）基因组突变率最高提升100倍时，对适应性演化的影响。为此，我们在实验室中对经过基因编辑、拥有四种不同突变率的无性繁殖大肠杆菌菌株的多个重复种群进行了3000代的演化培养。我们检测了演化后的种群在原始培养环境以及90余种新型化学环境中的生长能力。此外，我们还对这些种群进行了全基因组群体测序。尽管突变率更高的种群积累了更高的遗传多样性，但这一……