Fraser Christophe, Hanage William P, Spratt Brian G
Department of Infectious Disease Epidemiology, St. Mary's Hospital Campus, Imperial College London, Norfolk Place, London W2 1PG, United Kingdom.
Proc Natl Acad Sci U S A. 2005 Feb 8;102(6):1968-73. doi: 10.1073/pnas.0406993102. Epub 2005 Jan 31.
Understanding bacterial population genetics is vital for interpreting the response of bacterial populations to selection pressures such as antibiotic treatment or vaccines targeted at only a subset of strains. The evolution of transmissible bacteria occurs by mutation and localized recombination and is influenced by epidemiological as well as molecular processes. We demonstrate that the observed population genetic structure of three important human pathogens, Streptococcus pneumoniae, Neisseria meningitidis, and Staphylococcus aureus, can be explained by using a simple evolutionary model that is based on neutral mutational drift, modulated by recombination, and which incorporates the impact of epidemic transmission in local populations. The predictions of this neutral "microepidemic" model are found to closely fit observed genetic relatedness distributions of bacteria sampled from their natural population, and it provides estimates of the relative rate of recombination that agree well with empirical estimates. The analysis suggests the emergence of neutral bacterial population structure from overlapping microepidemics within clustered host populations and provides insight into the nature and size distribution of these clusters. These findings challenge the assumption that strains of bacterial pathogens differ markedly in relative fitness.
了解细菌群体遗传学对于解释细菌群体对诸如抗生素治疗或仅针对部分菌株的疫苗等选择压力的反应至关重要。可传播细菌的进化通过突变和局部重组发生,并受到流行病学以及分子过程的影响。我们证明,通过使用一个简单的进化模型可以解释三种重要人类病原体——肺炎链球菌、脑膜炎奈瑟菌和金黄色葡萄球菌——所观察到的群体遗传结构。该模型基于中性突变漂移,受重组调节,并纳入了局部群体中流行传播的影响。发现这个中性“微流行”模型的预测与从自然群体中采样的细菌所观察到的遗传相关性分布非常吻合,并且它提供的重组相对速率估计与经验估计值非常一致。分析表明,在聚集的宿主群体中,重叠的微流行导致了中性细菌群体结构的出现,并深入了解了这些群体的性质和大小分布。这些发现挑战了细菌病原体菌株在相对适应性上存在显著差异的假设。