Phylogenomic analysis of natural selection pressure in Streptococcus genomes.

Phylogenomic analysis of natural selection pressure in Streptococcus genomes.
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DOI:
10.1186/1471-2148-7-154
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发表时间:
2007-08-30
影响因子:
3.4
通讯作者:
Yang Z
Yang Z
中科院分区:
生物学2区
文献类型:
--
作者:
Anisimova M;Bielawski J;Dunn K;Yang Z

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在细菌病原体的比较分析中,通常的做法是区分两种类型的基因:(i)病原体及其非致病性亲属共享的基因(核心基因),以及(ii)仅在病原体中发现的基因(病原体特异性辅助基因)。我们没有试图先验地将基因划分成与致病性或多或少相关的集合,而是通过调查所有同源基因簇中自然选择的强度来分析链球菌属物种。链球菌属是由各种各样的致病性和寄生性谱系,我们将我们的研究结果与链球菌毒力因子的预先存在的知识。我们对1730个基因簇的分析揭示了136例阳性达尔文选择,我们认为这最有可能是由于宿主和病原体之间在分子水平上的拮抗相互作用。一个两步验证程序表明,积极的选择是稳健地确定在我们的基因组调查。我们发现没有证据支持病原体特异性辅助基因比核心基因更容易受到正选择的观点。事实上,我们甚至发现了一些通过正向选择进行的必要基因进化的案例。在正选择的基因簇中,很大一部分(29%)与毒力有关。最引人注目的发现是,已知相当一部分阳性选择基因在侵袭性疾病期间具有组织特异性表达模式。由于目前的表达数据远不全面,我们认为这一比例被低估了。我们的研究结果表明,病原体特异性基因,虽然一个流行的研究重点,并没有提供一个完整的图片毒力的进化动力学。这项研究和其他研究的结果支持这样一种观点,即核心基因和辅助基因的产物都参与了构成毒力分子基础的复杂网络。未来的工作应该寻求理解的核心和辅助基因的进化动力学作为一个功能的网络,他们参与。
In comparative analyses of bacterial pathogens, it has been common practice to discriminate between two types of genes: (i) those shared by pathogens and their non-pathogenic relatives (core genes), and (ii) those found exclusively in pathogens (pathogen-specific accessory genes). Rather than attempting to a priori delineate genes into sets more or less relevant to pathogenicity, we took a broad approach to the analysis of Streptococcus species by investigating the strength of natural selection in all clusters of homologous genes. The genus Streptococcus is comprised of a wide variety of both pathogenic and commensal lineages, and we relate our findings to the pre-existing knowledge of Streptococcus virulence factors. Our analysis of 1730 gene clusters revealed 136 cases of positive Darwinian selection, which we suggest is most likely to result from an antagonistic interaction between the host and pathogen at the molecular level. A two-step validation procedure suggests that positive selection was robustly identified in our genomic survey. We found no evidence to support the notion that pathogen specific accessory genes are more likely to be subject to positive selection than core genes. Indeed, we even uncovered a few cases of essential gene evolution by positive selection. Among the gene clusters subject to positive selection, a large fraction (29%) can be connected to virulence. The most striking finding was that a considerable fraction of the positively selected genes are also known to have tissue specific patterns of expression during invasive disease. As current expression data is far from comprehensive, we suggest that this fraction was underestimated. Our findings suggest that pathogen specific genes, although a popular focus of research, do not provide a complete picture of the evolutionary dynamics of virulence. The results of this study, and others, support the notion that the products of both core and accessory genes participate in complex networks that comprise the molecular basis of virulence. Future work should seek to understand the evolutionary dynamics of both core and accessory genes as a function of the networks in which they participate.
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