Local adaptation of Mycobacterium tuberculosis on the Tibetan Plateau
Local adaptation of Mycobacterium tuberculosis on the Tibetan Plateau
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DOI：
10.1073/pnas.2017831118
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发表时间：
2021-04-27
影响因子：
11.1
通讯作者：
Gao, Qian
中科院分区：
文献类型：
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作者：
Liu, Qingyun;Liu, Haican;Gao, Qian
结核分枝杆菌（Mycobacterium tuberculosis，Mtb）在全球传播过程中，经历了不同的地理环境和宿主种群。虽然当地的适应似乎是一个合理的模型来描述长期主机？病原体相互作用，这种模式的遗传证据是缺乏的。本研究对西藏高海拔地区576株结核分枝杆菌全基因组序列进行了分析。我们的研究结果表明，在连续引入一些祖先菌株后，西藏结核分枝杆菌种群在本地多样化，同时与中国低海拔平原地区的结核分枝杆菌种群保持严格的分离。目前的种群结构和估计的过去种群动态表明，现代北京亚系菌株，扩大了中国大部分地区和其他全球地区，并没有显示出在西藏的扩张优势。藏族菌株中的突变表现出比平原地区菌株更高的A > G/T > C转换比例，并且编码DNA修复酶的基因显示出正选择的证据。此外，长期西藏独家选择截短突变的巯基氧化还原酶编码sseA基因表明，结核分枝杆菌受到当地的选择压力与氧化应激。总的来说，西藏相对隔离人群中Mtb菌株的群体基因组学提供了Mtb适应当地环境的遗传证据。
During its global dispersal, Mycobacterium tuberculosis (Mtb) has encountered varied geographic environments and host populations. Although local adaptation seems to be a plausible model for describing long-term host?pathogen interactions, genetic evidence for this model is lacking. Here, we analyzed 576 wholegenome sequences of Mtb strains sampled from different regions of high-altitude Tibet. Our results show that, after sequential introduction of a few ancestral strains, the Tibetan Mtb population diversified locally while maintaining strict separation from the Mtb populations on the lower altitude plain regions of China. The current population structure and estimated past population dynamics suggest that the modern Beijing sublineage strains, which expanded over most of China and other global regions, did not show an expansion advantage in Tibet. The mutations in the Tibetan strains showed a higher proportion of A > G/T > C transitions than strains from the plain regions, and genes encoding DNA repair enzymes showed evidence of positive selection. Moreover, the long-term Tibetan exclusive selection for truncating mutations in the thiol-oxidoreductase encoding sseA gene suggests that Mtb was subjected to local selective pressures associated with oxidative stress. Collectively, the population genomics of Mtb strains in the relatively isolated population of Tibet provides genetic evidence that Mtb has adapted to local environments.