After the bottleneck: Genome-wide diversification of the Mycobacterium tuberculosis complex by mutation, recombination, and natural selection
After the bottleneck: Genome-wide diversification of the Mycobacterium tuberculosis complex by mutation, recombination, and natural selection
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DOI：
10.1101/gr.129544.111
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发表时间：
2012-04-01
期刊：
影响因子：
7
通讯作者：
Rocha, Eduardo P. C.
中科院分区：
文献类型：
--
作者：
Namouchi, Amine;Didelot, Xavier;Rocha, Eduardo P. C.
许多最致命的细菌病原体表现出低遗传多样性和性隔离。因此，最致命的人类病原体结核分枝杆菌被认为是无性繁殖的，并通过遗传漂变而进化。然而，它的基因组几乎没有显示出伴随的基因组退化迹象。我们分析了24个基因组，发现在编码关键适应功能的区域，包括VII型分泌系统和古老的水平转移毒力相关区域，存在过量的遗传多样性。四种不同的方法在结核分枝杆菌中显示出明显的重组迹象。重组区增加了高密度的多态性，因此许多被预测来自进化枝的外部。其中一些束与卡奈蒂分枝杆菌的序列相匹配。一般来说，重组引入了过量的非同义多样性，甚至更多的是非同义多样性的基因，例如细胞壁成分基因。导致非同义snp的突变在MTBC中被有效清除。，表现出净化选择的优势。MTBC突变对AT核苷酸的偏倚并没有被偏倚的基因转换所补偿，这表明自然选择也对同义变化起作用。综上所述，所有这些观察结果都表明，基因组中存在强烈的重组和选择印记，影响着非同义和同义位置。因此，与其他一些病原体和先前关于结核分枝杆菌的建议相反，这一谱系可能已经走出了其祖先的瓶颈，作为一种非常成功的病原体，通过突变、重组和自然选择的作用迅速多样化。
Many of the most virulent bacterial pathogens show low genetic diversity and sexual isolation. Accordingly, Mycobacterium tuberculosis, the deadliest human pathogen, is thought to be clonal and evolve by genetic drift. Yet, its genome shows few of the concomitant signs of genome degradation. We analyzed 24 genomes and found an excess of genetic diversity in regions encoding key adaptive functions including the type VII secretion system and the ancient horizontally transferred virulence-related regions. Four different approaches showed evident signs of recombination in M. tuberculosis. Recombination tracts add a high density of polymorphisms, and many are thus predicted to arise from outside the clade. Some of these tracts match Mycobacterium canettii sequences. Recombination introduced an excess of non-synonymous diversity in general and even more in genes expected to be under positive or diversifying selection, e.g., cell wall component genes. Mutations leading to non-synonymous SNPs are effectively purged in MTBC., which shows dominance of purifying selection. MTBC mutation bias toward AT nucleotides is not compensated by biased gene conversion, suggesting the action of natural selection also on synonymous changes. Together, all of these observations point to a strong imprint of recombination and selection in the genome affecting both non-synonymous and synonymous positions. Hence, contrary to some other pathogens and previous proposals concerning M. tuberculosis, this lineage may have come out of its ancestral bottleneck as a very successful pathogen that is rapidly diversifying by the action of mutation, recombination, and natural selection.