High-throughput sequencing provides insights into genome variation and evolution in Salmonella Typhi.
High-throughput sequencing provides insights into genome variation and evolution in Salmonella Typhi.
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DOI：
10.1038/ng.195
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发表时间：
2008-08
期刊：
影响因子：
30.8
通讯作者：
Dougan, Gordon
中科院分区：
文献类型：
--
作者：
Holt, Kathryn E.;Parkhill, Julian;Mazzoni, Camila J.;Roumagnac, Philippe;Weill, Francois-Xavier;Goodhead, Ian;Rance, Richard;Baker, Stephen;Maskell, Duncan J.;Wain, John;Dolecek, Christiane;Achtman, Mark;Dougan, Gordon
伤寒沙门氏菌血清型伤寒杆菌（Typhi）是一种仅感染人类并引发伤寒的细菌病原体，其分离株显示出有限的基因变异。我们使用454（罗氏）和Solexa（因美纳）技术对19株伤寒杆菌分离株进行了全基因组测序。所选取的分离株包括先前已测序的CT18和Ty2分离株，以代表系统发育树中的主要分支节点。比较分析显示，几乎没有证据表明分离株之间存在净化选择、抗原变异或重组。相反，伤寒杆菌种群的进化似乎以基因功能的持续丧失为特征，这与有效种群规模较小相符。缺乏由免疫选择驱动的抗原变异的证据，这与伤寒杆菌中对抗生素耐药性突变的强烈适应性选择形成对比。所观察到的基因隔离和漂变模式与所提出的伤寒杆菌无症状携带者作为这种病原体的主要储存库的关键作用相符，这凸显了识别和治疗携带者的必要性。
Isolates of Salmonella enterica serovar Typhi (Typhi), a human-restricted bacterial pathogen that causes typhoid, show limited genetic variation. We generated whole-genome sequences for 19 Typhi isolates using 454 (Roche) and Solexa (Illumina) technologies. Isolates, including the previously sequenced CT18 and Ty2 isolates, were selected to represent major nodes in the phylogenetic tree. Comparative analysis showed little evidence of purifying selection, antigenic variation or recombination between isolates. Rather, evolution in the Typhi population seems to be characterized by ongoing loss of gene function, consistent with a small effective population size. The lack of evidence for antigenic variation driven by immune selection is in contrast to strong adaptive selection for mutations conferring antibiotic resistance in Typhi. The observed patterns of genetic isolation and drift are consistent with the proposed key role of asymptomatic carriers of Typhi as the main reservoir of this pathogen, highlighting the need for identification and treatment of carriers.
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