Bacterial Genetic Signatures of Human Social Phenomena among M-tuberculosis from an Aboriginal Canadian Population
Bacterial Genetic Signatures of Human Social Phenomena among M-tuberculosis from an Aboriginal Canadian Population
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DOI：
10.1093/molbev/msp261
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发表时间：
2010-02-01
影响因子：
10.7
通讯作者：
Feldman, Marcus W.
中科院分区：
文献类型：
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作者：
Pepperell, Caitlin;Hoeppner, Vernon H.;Feldman, Marcus W.
尽管全球分布广泛且疾病表型高度可变，但结核分枝杆菌分离株之间几乎没有 DNA 序列多样性。此外，许多区域人口遗传调查揭示了一种刻板结构，其中单一克隆、谱系或进化枝构成了人口的大多数。通常认为显性克隆具有高度适应性，即结核分枝杆菌种群的整体结构是正选择的结果。为了检验这一假设，我们分析了加拿大萨斯喀彻温省原住民社区现存细菌种群的遗传数据。细菌种群的人口统计参数是根据东道社区流行性结核病发病以来近 130 年来收集的流行病学档案数据估算得出的。根据中性理论预期测试细菌遗传数据，并通过系统发育分析研究结核分枝杆菌的局部进化史。我们的研究结果与细菌群体的正选择不一致。相反，我们发现了持续数十年的创始人效应以及细菌群体内基因流动的障碍。模拟实验表明，这些中性影响的结合可能会导致结核分枝杆菌种群的刻板结构。种群结构的某些方面暗示了背景选择，数据总体上与种群瓶颈、细分和背景选择的综合影响一致。中性现象，即种群内的瓶颈和分区，是对结核分枝杆菌进化的显着影响，并可能导致该物种内观察到的遗传多样性受到限制。考虑到这些影响，需要一个复杂的进化模型来定义不同结核分枝杆菌谱系的相对适应性，并最终揭示其作为病原体成功的遗传基础。
Despite a widespread global distribution and highly variable disease phenotype, there is little DNA sequence diversity among isolates of Mycobacterium tuberculosis. In addition, many regional population genetic surveys have revealed a stereotypical structure in which a single clone, lineage, or clade makes up the majority of the population. It is often assumed that dominant clones are highly adapted, that is, the overall structure of M. tuberculosis populations is the result of positive selection. In order to test this assumption, we analyzed genetic data from extant populations of bacteria circulating in Aboriginal communities in Saskatchewan, Canada. Demographic parameters of the bacterial population were estimated from archival epidemiological data collected over similar to 130 years since the onset of epidemic tuberculosis in the host communities. Bacterial genetic data were tested against neutral theory expectations and the local evolutionary history of M. tuberculosis investigated by phylogenetic analysis. Our findings are not consistent with positive selection on the bacterial population. Instead, we uncovered founder effects persisting over decades and barriers to gene flow within the bacterial population. Simulation experiments suggested that a combination of these neutral influences could result in the stereotypical structure of M. tuberculosis populations. Some aspects of population structure were suggestive of background selection, and data were on the whole consistent with combined effects of population bottlenecks, subdivision, and background selection. Neutral phenomena, namely, bottlenecks and partitions within populations, are prominent influences on the evolution of M. tuberculosis and likely contribute to restricted genetic diversity observed within this species. Given these influences, a complex evolutionary model will be required to define the relative fitness of different M. tuberculosis lineages and, ultimately, to uncover the genetic basis for its success as a pathogen.