High frequency of hotspot mutations in core genes of Escherichia coli due to short-term positive selection
High frequency of hotspot mutations in core genes of Escherichia coli due to short-term positive selection
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DOI：
10.1073/pnas.0906217106
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发表时间：
2009-07-28
影响因子：
11.1
通讯作者：
Sokurenko, Evgeni V.
中科院分区：
文献类型：
--
作者：
Chattopadhyay, Sujay;Weissman, Scott J.;Sokurenko, Evgeni V.
构成细菌基因组的普遍存在的骨架的核心基因不受频繁的水平转移的影响，并且通常不被认为有助于细菌病原体的适应性进化。然而，我们确定，大肠杆菌基因组中至少有三分之一，甚至可能超过一半的核心基因是通过在相同氨基酸位置重复替换取代而靶向的热点突变。热点突变的发生是由正选择驱动的，因为它们的发生率显著高于单独随机机会的预期，并且基因内重组和增加的突变性都不能解释观察到的模式。另外，Escherichia E.大肠杆菌菌株具有比致病菌株显著更低的突变基因频率和每个基因组的突变。E.引起肠外感染的大肠杆菌菌株以最高的速率积累热点突变，而在志贺氏菌分离株中发现的突变基因总数最多，表明这种突变的病理适应性。绝大多数热点突变是最近的进化起源，这意味着短期的正选择，其中适应性突变反复出现，但不会在自然循环中持续很长时间。这种动态模式与毒力进化的源库模型相一致。
Core genes comprising the ubiquitous backbone of bacterial genomes are not subject to frequent horizontal transfer and generally are not thought to contribute to the adaptive evolution of bacterial pathogens. We determined, however, that at least one-third and possibly more than one-half of the core genes in Escherichia coli genomes are targeted by repeated replacement substitutions in the same amino acid positions-hotspot mutations. Occurrence of hotspot mutations is driven by positive selection, as their rate is significantly higher than expected by random chance alone, and neither intragenic recombination nor increased mutability can explain the observed patterns. Also, commensal E. coli strains have a significantly lower frequency of mutated genes and mutations per genome than pathogenic strains. E. coli strains causing extra-intestinal infections accumulate hotspot mutations at the highest rate, whereas the highest total number of mutated genes has been found among Shigella isolates, suggesting the pathoadaptive nature of such mutations. The vast majority of hotspot mutations are of recent evolutionary origin, implying short-term positive selection, where adaptive mutations emerge repeatedly but are not sustained in natural circulation for long. Such pattern of dynamics is consistent with source-sink model of virulence evolution.