Population genomics of Mycobacterium tuberculosis in the Inuit
Population genomics of Mycobacterium tuberculosis in the Inuit
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DOI：
10.1073/pnas.1507071112
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发表时间：
2015-11-03
影响因子：
11.1
通讯作者：
Behr, Marcel A.
中科院分区：
文献类型：
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作者：
Lee, Robyn S.;Radomski, Nicolas;Behr, Marcel A.
魁北克省努纳维克患有流行性结核病 (TB)，发病率比加拿大平均水平高 50 倍。该地区的分子研究记录了结核分枝杆菌分离株中有限的细菌遗传多样性，这与创始菌株和/或持续传播一致。我们对来自 11 个地理位置偏僻的村庄的 163 株结核分枝杆菌分离株进行了全基因组测序，以提供该环境中细菌遗传多样性的高分辨率图像。所有分离株均为谱系 4（欧美），存在两个亚谱系（主要，n = 153；次要，n = 10）。在主要亚谱系分离株中，平均有 46 个成对单核苷酸多态性 (SNP)，最近的共同祖先 (MRCA) 出现在 20 世纪初。一个村庄内的分离株对的 SNP 显着少于来自不同村庄的分离株对（中位数：6 对 47，P < 0.00005），表明大多数传播发生在村庄内。努纳维克内结核分枝杆菌多样化后，非同义 SNP 过多：非同义替换率与同义替换率 (dN/dS) 之比 (dN/dS) 在 MRCA 之前为 0.534，但随后为 0.777 (P = 0.010)。在所有基因类别中均检测到非同义 SNP，反对正向选择并倾向于放松纯化选择的遗传漂变。自 MRCA 以来，有 28 个基因被部分或完全删除，包括先前报道的对结核分枝杆菌生长至关重要的基因，支持了后一种可能性。我们的研究结果表明，结核分枝杆菌在该地区的流行病学成功更有可能是由于有利于结核病传播的环境，而不是特别适应的菌株。
Nunavik, Quebec suffers from epidemic tuberculosis (TB), with an incidence 50-fold higher than the Canadian average. Molecular studies in this region have documented limited bacterial genetic diversity among Mycobacterium tuberculosis isolates, consistent with a founder strain and/or ongoing spread. We have used whole-genome sequencing on 163 M. tuberculosis isolates from 11 geographically isolated villages to provide a high-resolution portrait of bacterial genetic diversity in this setting. All isolates were lineage 4 (Euro-American), with two sublineages present (major, n = 153; minor, n = 10). Among major sublineage isolates, there was a median of 46 pairwise single-nucleotide polymorphisms (SNPs), and the most recent common ancestor (MRCA) was in the early 20th century. Pairs of isolates within a village had significantly fewer SNPs than pairs from different villages (median: 6 vs. 47, P < 0.00005), indicating that most transmission occurs within villages. There was an excess of nonsynonymous SNPs after the diversification of M. tuberculosis within Nunavik: The ratio of nonsynonymous to synonymous substitution rates (dN/dS) was 0.534 before the MRCA but 0.777 subsequently (P = 0.010). Nonsynonymous SNPs were detected across all gene categories, arguing against positive selection and toward genetic drift with relaxation of purifying selection. Supporting the latter possibility, 28 genes were partially or completely deleted since the MRCA, including genes previously reported to be essential for M. tuberculosis growth. Our findings indicate that the epidemiologic success of M. tuberculosis in this region is more likely due to an environment conducive to TB transmission than a particularly well-adapted strain.