Unité Mixte de Recherche 1137, Infection, Antimicrobiens, Modélisation, Evolution, INSERM, Université Paris Diderot, 75018 Paris, France.
Unité Mixte de Recherche 5525, Technologies de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications Grenoble, Université Grenoble Alpes, CNRS, 38000 Grenoble, France.
Proc Natl Acad Sci U S A. 2017 Oct 24;114(43):E9026-E9035. doi: 10.1073/pnas.1705887114. Epub 2017 Oct 10.
Understanding the extreme variation among bacterial genomes remains an unsolved challenge in evolutionary biology, despite long-standing debate about the relative importance of natural selection, mutation, and random drift. A potentially important confounding factor is the variation in mutation rates between lineages and over evolutionary history, which has been documented in several species. Mutation accumulation experiments have shown that hypermutability can erode genomes over short timescales. These results, however, were obtained under conditions of extremely weak selection, casting doubt on their general relevance. Here, we circumvent this limitation by analyzing genomes from mutator populations that arose during a long-term experiment with , in which populations have been adaptively evolving for >50,000 generations. We develop an analytical framework to quantify the relative contributions of mutation and selection in shaping genomic characteristics, and we validate it using genomes evolved under regimes of high mutation rates with weak selection (mutation accumulation experiments) and low mutation rates with strong selection (natural isolates). Our results show that, despite sustained adaptive evolution in the long-term experiment, the signature of selection is much weaker than that of mutational biases in mutator genomes. This finding suggests that relatively brief periods of hypermutability can play an outsized role in shaping extant bacterial genomes. Overall, these results highlight the importance of genomic draft, in which strong linkage limits the ability of selection to purge deleterious mutations. These insights are also relevant to other biological systems evolving under strong linkage and high mutation rates, including viruses and cancer cells.
尽管关于自然选择、突变和随机漂变的相对重要性的争论由来已久，但理解细菌基因组之间的极端变异仍然是进化生物学中的一个未解决的挑战。一个潜在的重要混杂因素是谱系之间和进化历史中突变率的变化，这在几个物种中已经有记录。突变积累实验表明，超突变性可以在短时间内侵蚀基因组。然而，这些结果是在极其微弱的选择条件下获得的，这使得它们的普遍相关性受到怀疑。在这里，我们通过分析在一个长期的实验中产生的突变体种群的基因组来规避这一限制，在这个实验中，种群已经适应进化了超过 50000 代。我们开发了一种分析框架来量化突变和选择在塑造基因组特征方面的相对贡献，并使用在弱选择（突变积累实验）下具有高突变率和在强选择（自然分离株）下具有低突变率的条件下进化的基因组对其进行了验证。我们的结果表明，尽管在长期实验中持续进行适应性进化，但选择的特征比突变体基因组中突变偏倚的特征弱得多。这一发现表明，相对短暂的高突变性时期可以在塑造现存细菌基因组方面发挥重要作用。总的来说，这些结果强调了基因组草图的重要性，其中强连锁限制了选择清除有害突变的能力。这些见解也与其他在强连锁和高突变率下进化的生物系统相关，包括病毒和癌细胞。
