<p>Assembly and annotation statistics.</p>
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Murine typhus, caused by infection with Rickettsia typhi, is a neglected disease contributing to infectious disease burden in south- and southeast Asia. Despite its importance, we have minimal knowledge of the genomics of R. typhi, with only four complete genomes being sequenced prior to this work. We sequenced a further 25 genomes including historical strains collected before 1976 from both human and rat hosts, and recent genomes isolated from patients at a single hospital in Laos. Whole genome SNP analysis reveals extremely low levels of genetic diversity across the 29 genomes, with overall nucleotide diversity (π) of 1.27e-05 and evidence of purifying selection, and a minimal pan-genome. Phylogenetic analysis shows clustering of the genome by historic or modern origin, with the exception of one modern strain which is most closely related to historic strains from Thailand, and no clustering by host origin. The highly conserved genome of R. typhi suggests strong constraints on genome evolution in this obligate intracellular parasite, and has implications for the design of future murine typhus diagnostic tools and vaccines.
由斑疹伤寒立克次体(Rickettsia typhi)感染所致的鼠型斑疹伤寒,是一类被忽视的传染病,在南亚及东南亚地区构成了传染病负担的重要组成部分。尽管该病具有重要公共卫生意义,学界对斑疹伤寒立克次体的基因组学认知仍极为匮乏,此前仅完成4株完整基因组的测序工作。本研究新增测序25株基因组,其中涵盖1976年前采集的、分别来源于人类与啮齿类宿主的历史菌株,以及近期从老挝某医院患者体内分离得到的毒株。全基因组单核苷酸多态性(Single Nucleotide Polymorphism, SNP)分析显示,29株基因组的遗传多样性水平极低,整体核苷酸多样性(π)为1.27×10^-5,且存在纯化选择迹象,泛基因组规模极小。系统发育分析表明,基因组按历史或现代来源聚类,但有1株现代毒株与泰国的历史菌株亲缘关系最近,属于例外,且未出现按宿主来源聚类的情况。斑疹伤寒立克次体基因组的高度保守性,提示这种专性胞内寄生细菌的基因组演化受到极强约束,该发现对未来鼠型斑疹伤寒诊断工具与疫苗的研发具有重要指导价值。




