Evolutionary dynamics of bacteria in a human host environment
Evolutionary dynamics of bacteria in a human host environment
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DOI：
10.1073/pnas.1018249108
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发表时间：
2011-05-03
影响因子：
11.1
通讯作者：
Molin, Soren
中科院分区：
文献类型：
--
作者：
Yang, Lei;Jelsbak, Lars;Molin, Soren
实验室进化实验取得了有关生物适应和基因组进化的重要发现。然而，自然系统缺乏对长期演化的持续监测，限制了我们对这些原地过程的理解。在这里，我们描述了临床上重要的机会性细菌病原体铜绿假单胞菌谱系的进化动态，它在超过 200,000 个细菌代中适应了几个囊性纤维化患者的气道，并提供了自然环境中细菌突变率的估计。与基于体外进化实验的预测相反，尽管宿主环境高度结构化且复杂，但我们记录了进化谱系的有限多样化。值得注意的是，该谱系经历了由少量具有多效性效应的突变引起的快速适应的初始阶段，随后是一段具有有限表型变化和负选择基因组特征的遗传漂变时期，这表明不断进化的谱系已达到适应性景观的主要适应峰值。这与之前从长期体外进化实验中持续正向选择的发现形成鲜明对比。感染细菌的进化表型进一步表明，机会性病原体已转变为囊性纤维化患者的主要病原体。
Laboratory evolution experiments have led to important findings relating organism adaptation and genomic evolution. However, continuous monitoring of long-term evolution has been lacking for natural systems, limiting our understanding of these processes in situ. Here we characterize the evolutionary dynamics of a lineage of a clinically important opportunistic bacterial pathogen, Pseudomonas aeruginosa, as it adapts to the airways of several individual cystic fibrosis patients over 200,000 bacterial generations, and provide estimates of mutation rates of bacteria in a natural environment. In contrast to predictions based on in vitro evolution experiments, we document limited diversification of the evolving lineage despite a highly structured and complex host environment. Notably, the lineage went through an initial period of rapid adaptation caused by a small number of mutations with pleiotropic effects, followed by a period of genetic drift with limited phenotypic change and a genomic signature of negative selection, suggesting that the evolving lineage has reached a major adaptive peak in the fitness landscape. This contrasts with previous findings of continued positive selection from long-term in vitro evolution experiments. The evolved phenotype of the infecting bacteria further suggests that the opportunistic pathogen has transitioned to become a primary pathogen for cystic fibrosis patients.