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比较基因组学视角下的立克次体进化。

Rickettsial evolution in the light of comparative genomics.

机构信息

Unit for Research on Emergent and Tropical Infectious Diseases, CNRS-IRD UMR 6236 IFR48, Faculty of Medicine, University of the Mediterranean, Marseilles, France.

出版信息

Biol Rev Camb Philos Soc. 2011 May;86(2):379-405. doi: 10.1111/j.1469-185X.2010.00151.x. Epub 2010 Aug 17.

DOI:10.1111/j.1469-185X.2010.00151.x
PMID:20716256
Abstract

Rickettsia are best known as strictly intracellular vector-borne bacteria that cause mild to severe diseases in humans and other animals. Recent advances in molecular tools and biological experiments have unveiled a wide diversity of Rickettsia spp. that include species with a broad host range and some species that act as endosymbiotic associates. Molecular phylogenies of Rickettsia spp. contain some ambiguities, such as the position of R. canadensis and relationships within the spotted fever group. In the modern era of genomics, with an ever-increasing number of sequenced genomes, there is enhanced interest in the use of whole-genome sequences to understand pathogenesis and assess evolutionary relationships among rickettsial species. Rickettsia have small genomes (1.1-1.5 Mb) as a result of reductive evolution. These genomes contain split genes, gene remnants and pseudogenes that, owing to the colinearity of some rickettsial genomes, may represent different steps of the genome degradation process. Genomics reveal extreme genome reduction and massive gene loss in highly vertebrate-pathogenic Rickettsia compared to less virulent or endosymbiotic species. Information gleaned from rickettsial genomics challenges traditional concepts of pathogenesis that focused primarily on the acquisition of virulence factors. Another intriguing phenomenon about the reduced rickettsial genomes concerns the large fraction of non-coding DNA and possible functionality of these "non-coding" sequences, because of the high conservation of these regions. Despite genome streamlining, Rickettsia spp. contain gene families, selfish DNA, repeat palindromic elements and genes encoding eukaryotic-like motifs. These features participate in sequence and functional diversity and may play a crucial role in adaptation to the host cell and pathogenesis. Genome analyses have identified a large fraction of mobile genetic elements, including plasmids, suggesting the possibility of lateral gene transfer in these intracellular bacteria. Phylogenetic analyses have identified several candidates for horizontal gene acquisition among Rickettsia spp. including tra, pat2, and genes encoding for the type IV secretion system and ATP/ADP translocase that may have been acquired from bacteria living in amoebae. Gene loss, gene duplication, DNA repeats and lateral gene transfer all have shaped rickettsial genome evolution. A comprehensive analysis of the entire genome, including genes and non-coding DNA, will help to unlock the mysteries of rickettsial evolution and pathogenesis.

摘要

立克次体是众所周知的严格细胞内的载体传播细菌,可引起人类和其他动物的轻度至重度疾病。分子工具和生物实验的最新进展揭示了广泛的立克次体多样性,包括具有广泛宿主范围的物种和一些作为内共生伙伴的物种。立克次体的分子系统发育存在一些模糊性,例如 R. canadensis 的位置和斑点热群内的关系。在基因组学的现代时代,随着越来越多的基因组测序,人们对手册基因组序列的使用越来越感兴趣,以了解发病机制并评估立克次体物种之间的进化关系。由于还原进化,立克次体的基因组很小(1.1-1.5 Mb)。这些基因组包含分裂基因、基因残基和假基因,由于一些立克次体基因组的共线性,这些基因可能代表基因组降解过程的不同步骤。基因组学揭示了高度脊椎动物致病性的立克次体与低毒力或内共生物种相比,基因组的极度减少和大量基因丢失。从立克次体基因组学中获取的信息挑战了主要关注毒力因子获取的传统发病机制概念。关于简化的立克次体基因组的另一个有趣现象是,大量非编码 DNA 的存在以及这些“非编码”序列的可能功能,因为这些区域的高度保守性。尽管基因组简化,立克次体仍包含基因家族、自私 DNA、重复回文元件和编码真核样基序的基因。这些特征参与序列和功能多样性,并可能在适应宿主细胞和发病机制中发挥关键作用。基因组分析确定了大量移动遗传元件,包括质粒,表明这些细胞内细菌可能存在横向基因转移。系统发育分析确定了 Rickettsia spp. 之间水平基因获取的几个候选者,包括 tra、pat2 和编码 IV 型分泌系统和 ATP/ADP 易位酶的基因,这些基因可能来自生活在变形虫中的细菌。基因丢失、基因复制、DNA 重复和横向基因转移都塑造了立克次体基因组的进化。对整个基因组,包括基因和非编码 DNA 的全面分析,将有助于揭示立克次体进化和发病机制的奥秘。

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