Evolution and diversity of clonal bacteria: the paradigm of Mycobacterium tuberculosis.

Evolution and diversity of clonal bacteria: the paradigm of Mycobacterium tuberculosis.
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DOI:
10.1371/journal.pone.0001538
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发表时间:
2008-02-06
期刊:
影响因子:
3.7
通讯作者:
Gicquel B
Gicquel B
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Dos Vultos T;Mestre O;Rauzier J;Golec M;Rastogi N;Rasolofo V;Tonjum T;Sola C;Matic I;Gicquel B

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结核分枝杆菌复合种具有相对静态的基因组和99.9%的核苷酸序列同源性。研究这种单态细菌的进化史是一项艰巨而具有挑战性的任务。我们发现,对来自世界各地的结核分枝杆菌复合菌株进行DNA修复、重组和复制(3R)基因的单核苷酸多态性(SNP)分析,与看家基因相比,产生了令人惊讶的高水平多态,使得有可能区分本研究分析的80%的临床分离株。生物信息学分析表明,这些多态中的大量具有潜在的危害性。同义和非同义变异的位点频谱比较和Ka/Ks比率分析表明,对这些基因的一般负/净化选择可能导致次优的3R系统活性。反过来,3R基因的松弛保真度可能允许出现适应性变异,其中一些会存活下来。此外,基于3R的系统发育树是区分结核分枝杆菌复杂株系的新工具。这种情况,以及随之而来的基因组维护的保真度不足,可能是抗生素耐药性、生存适合性和致病性进化的起点,可能在某些压力情况下赋予选择性优势。这些发现表明,3R基因可能在结核分枝杆菌等高克隆细菌的进化过程中发挥重要作用。它们还通过开发高分辨率工具,促进对这些细菌的进一步流行病学研究。随着更多的微生物基因组被测序,我们的结果为基于3R基因的其他高度克隆细菌的适应和进化研究打开了大门。
Mycobacterium tuberculosis complex species display relatively static genomes and 99.9% nucleotide sequence identity. Studying the evolutionary history of such monomorphic bacteria is a difficult and challenging task. We found that single-nucleotide polymorphism (SNP) analysis of DNA repair, recombination and replication (3R) genes in a comprehensive selection of M. tuberculosis complex strains from across the world, yielded surprisingly high levels of polymorphisms as compared to house-keeping genes, making it possible to distinguish between 80% of clinical isolates analyzed in this study. Bioinformatics analysis suggests that a large number of these polymorphisms are potentially deleterious. Site frequency spectrum comparison of synonymous and non-synonymous variants and Ka/Ks ratio analysis suggest a general negative/purifying selection acting on these sets of genes that may lead to suboptimal 3R system activity. In turn, the relaxed fidelity of 3R genes may allow the occurrence of adaptive variants, some of which will survive. Furthermore, 3R-based phylogenetic trees are a new tool for distinguishing between M. tuberculosis complex strains. This situation, and the consequent lack of fidelity in genome maintenance, may serve as a starting point for the evolution of antibiotic resistance, fitness for survival and pathogenicity, possibly conferring a selective advantage in certain stressful situations. These findings suggest that 3R genes may play an important role in the evolution of highly clonal bacteria, such as M. tuberculosis. They also facilitate further epidemiological studies of these bacteria, through the development of high-resolution tools. With many more microbial genomes being sequenced, our results open the door to 3R gene-based studies of adaptation and evolution of other, highly clonal bacteria.
DOI: 10.1099/00221287-144-5-1189
发表时间: 1998-05-01
期刊: MICROBIOLOGY-UK
影响因子: --
作者:
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通讯作者: Meeker-O'Connell, WA
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发表时间: 1998-09-01
影响因子: 3.6
作者:
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