链球菌和葡萄球菌超抗原的进化途径。

Evolutionary paths of streptococcal and staphylococcal superantigens.

机构信息

Department of Infectious Diseases, National Center for Global Health and Medicine, Tokyo 162-8655, Japan.

出版信息

BMC Genomics. 2012 Aug 17;13:404. doi: 10.1186/1471-2164-13-404.

BACKGROUND

Streptococcus pyogenes (GAS) harbors several superantigens (SAgs) in the prophage region of its genome, although speG and smez are not located in this region. The diversity of SAgs is thought to arise during horizontal transfer, but their evolutionary pathways have not yet been determined. We recently completed sequencing the entire genome of S. dysgalactiae subsp. equisimilis (SDSE), the closest relative of GAS. Although speG is the only SAg gene of SDSE, speG was present in only 50% of clinical SDSE strains and smez in none. In this study, we analyzed the evolutionary paths of streptococcal and staphylococcal SAgs.

RESULTS

We compared the sequences of the 12-60 kb speG regions of nine SDSE strains, five speG(+) and four speG(-). We found that the synteny of this region was highly conserved, whether or not the speG gene was present. Synteny analyses based on genome-wide comparisons of GAS and SDSE indicated that speG is the direct descendant of a common ancestor of streptococcal SAgs, whereas smez was deleted from SDSE after SDSE and GAS split from a common ancestor. Cumulative nucleotide skew analysis of SDSE genomes suggested that speG was located outside segments of steeper slopes than the stable region in the genome, whereas the region flanking smez was unstable, as expected from the results of GAS. We also detected a previously undescribed staphylococcal SAg gene, selW, and a staphylococcal SAg -like gene, ssl, in the core genomes of all Staphylococcus aureus strains sequenced. Amino acid substitution analyses, based on dN/dS window analysis of the products encoded by speG, selW and ssl suggested that all three genes have been subjected to strong positive selection. Evolutionary analysis based on the Bayesian Markov chain Monte Carlo method showed that each clade included at least one direct descendant.

CONCLUSIONS

Our findings reveal a plausible model for the comprehensive evolutionary pathway of streptococcal and staphylococcal SAgs.

背景

化脓性链球菌 (GAS) 在其基因组的前噬菌体区域中含有几种超抗原 (SAg)，尽管 speG 和 smez 并不位于该区域。SAg 的多样性被认为是在水平转移过程中产生的，但它们的进化途径尚未确定。我们最近完成了对 GAS 最接近的亲缘种无乳链球菌亚种 equisimilis (SDSE) 的全基因组测序。虽然 speG 是 SDSE 的唯一 SAg 基因，但 speG 仅存在于 50%的临床 SDSE 菌株中，而 smez 则不存在。在这项研究中，我们分析了链球菌和葡萄球菌 SAg 的进化途径。

结果

我们比较了 9 株 SDSE 菌株 12-60kb speG 区的序列，其中 5 株为 speG(+)，4 株为 speG(-)。我们发现，无论 speG 基因是否存在，该区域的基因排列高度保守。基于 GAS 和 SDSE 全基因组比较的基因排列分析表明，speG 是链球菌 SAg 共同祖先的直接后代，而 smez 则是在 SDSE 和 GAS 从共同祖先分离后从 SDSE 中缺失的。SDSE 基因组累积核苷酸倾斜分析表明，speG 位于基因组中较陡斜率段之外的位置，而 smez 侧翼区域则不稳定，这与 GAS 的结果一致。我们还在所有测序的金黄色葡萄球菌核心基因组中检测到了一个以前未描述的葡萄球菌 SAg 基因 selW 和一个葡萄球菌 SAg 样基因 ssl。基于 speG、selW 和 ssl 编码产物的 dN/dS 窗口分析的氨基酸取代分析表明，这三个基因都受到了强烈的正选择。基于贝叶斯马尔可夫链蒙特卡罗法的进化分析表明，每个分支至少包含一个直接后代。