Data from: Mutator genomes decay, despite sustained fitness gains, in a long-term experiment with bacteria

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 Escherichia coli, 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.

尽管演化生物学领域长期以来围绕自然选择、突变与随机漂变的相对重要性存在诸多争论，但解析细菌基因组间的极端差异仍是一道尚未解决的科学难题。一个可能带来重要混淆效应的因素是不同谱系间以及演化历程中突变率的差异，这一现象已在多个物种中被观测记录。突变积累实验已证实，高突变性可在短时间尺度上对基因组造成侵蚀。然而，这类实验结果均是在选择压极弱的条件下获得的，这使得其普适性受到了质疑。本研究通过分析大肠杆菌（Escherichia coli）长期演化实验中出现的突变体种群基因组，规避了上述局限——该实验中的种群已适应性演化超过50000代。我们构建了一套分析框架，用于量化突变与选择在塑造基因组特征过程中的相对贡献，并分别以高突变率弱选择条件下演化的基因组（即突变积累实验样本）与低突变率强选择条件下演化的基因组（即自然分离株样本）对该框架进行了验证。研究结果显示，尽管该长期实验中的种群经历了持续的适应性演化，但在突变体基因组中，选择留下的分子信号远弱于突变偏倚所带来的信号。这一发现表明，相对短暂的高突变阶段，可能在现存细菌基因组的塑造过程中发挥远超预期的重要作用。总体而言，本研究结果凸显了基因组搭车效应（genomic draft）的重要性——在该效应下，紧密连锁会限制选择清除有害突变的能力。这些研究结论同样适用于其他处于强连锁与高突变率环境下演化的生物系统，例如病毒与癌细胞。