J-Western Forms of Helicobacter pylori cagA Constitute a Distinct Phylogenetic Group with a Widespread Geographic Distribution
J-Western Forms of Helicobacter pylori cagA Constitute a Distinct Phylogenetic Group with a Widespread Geographic Distribution
复制标题
DOI：
10.1128/jb.06340-11
复制
发表时间：
2012-03-01
影响因子：
3.2
通讯作者：
Cover, Timothy L.
中科院分区：
文献类型：
--
作者：
Duncan, Stacy S.;Valk, Pieter L.;Cover, Timothy L.
表达细菌癌蛋白CagA的幽门螺杆菌菌株的慢性感染可增加胃癌的风险。虽然对西方、东亚和美洲印第安人cagA序列的起源和分子进化了解很多，但对第四组被称为“J-Western”的cagA序列的了解相对较少，该序列主要在日本冲绳的菌株中检测到。我们在这里表明，J-Western cagA序列具有比以前认识到的更广泛的全球分布，发生在具有多个不同祖先来源的菌株中（基于多位点序列分型[MLST]分析），并且最近没有出现。如通过比较Western和J-Western形式的CagA所示，存在45个固定或几乎固定的氨基酸差异，并且J-Western形式含有独特的4个氨基酸插入。同义位点的平均核苷酸多样性（pi（s））在J-Western组中略低于西方和东亚组（分别为0.066、0.086和0.083），这表明三组具有可比性，但不相等，有效的群体大小。J-Western组的降低的pi（s）归因于cagA的5'区域内的祖先重组事件。人口遗传学分析表明，在cagA区域编码EPIYA图案，东亚组进行了显着减少，有效的人口规模相比，西方和J-西方组，与积极的选择。最后，我们发现，J-Western cagA序列主要是在菌株生产的m2形式的分泌型VacA毒素，并提出这些功能相互作用的蛋白质共同进化，以优化胃定植能力的H。幽门。
Chronic infection with Helicobacter pylori strains expressing the bacterial oncoprotein CagA confers an increased risk of gastric cancer. While much is known about the ancestry and molecular evolution of Western, East Asian, and Amerindian cagA sequences, relatively little is understood about a fourth group, known as "J-Western," which has been detected mainly in strains from Okinawa, Japan. We show here that J-Western cagA sequences have a more widespread global distribution than previously recognized, occur in strains with multiple different ancestral origins (based on multilocus sequence typing [MLST] analysis), and did not arise recently. As shown by comparisons of Western and J-Western forms of CagA, there are 45 fixed or nearly fixed amino acid differences, and J-Western forms contain a unique 4-amino-acid insertion. The mean nucleotide diversity of synonymous sites (pi(s)) is slightly lower in the J-Western group than in the Western and East Asian groups (0.066, 0.086, and 0.083, respectively), which suggests that the three groups have comparable, but not equivalent, effective population sizes. The reduced pi(s) of the J-Western group is attributable to ancestral recombination events within the 5' region of cagA. Population genetic analyses suggest that within the cagA region encoding EPIYA motifs, the East Asian group underwent a marked reduction in effective population size compared to the Western and J-Western groups, in association with positive selection. Finally, we show that J-Western cagA sequences are found mainly in strains producing m2 forms of the secreted VacA toxin and propose that these functionally interacting proteins coevolved to optimize the gastric colonization capacity of H. pylori.