Analysis of streptococcal CRISPRs from human saliva reveals substantial sequence diversity within and between subjects over time
Analysis of streptococcal CRISPRs from human saliva reveals substantial sequence diversity within and between subjects over time
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DOI：
10.1101/gr.111732.110
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发表时间：
2011-01-01
期刊：
影响因子：
7
通讯作者：
Relman, David A.
中科院分区：
文献类型：
--
作者：
Pride, David T.;Sun, Christine L.;Relman, David A.
病毒可能在人类微生物群落的进化中发挥重要作用。成簇的规则间隔的短回文重复序列 (CRISPR) 为细菌和古细菌提供了针对先前遇到的病毒的适应性免疫。人们对人类微生物群落成员中的 CRISPR 组成、CRISPR 位点变化的相对速率或不同个体的微生物群之间 CRISPR 位点有何不同知之甚少。我们在 11 至 17 个月的时间内收集了四名牙周健康受试者的唾液，并分析了具有相应链球菌重复序列的 CRISPR 序列，以提高我们对口腔链球菌适应性免疫库主要特征的理解。我们总共分析了 6859 个带有 CRISPR 的读数和 427,917 个细菌 16S rRNA 基因序列。我们发现共享 CRISPR 间隔区的核心（范围从 7% 到 22%）在每个受试者体内随着时间的推移保持稳定，但近三分之一的 CRISPR 间隔区在不同时间点之间发生变化。我们记录了每个受试者内的高间隔区多样性，表明不断添加新的 CRISPR 间隔区。受试者之间共享的 CRISPR 间隔区不超过 2%，这表明每个人都暴露于不同的病毒种群。我们检测到 CRISPR 间隔序列多样性随时间的变化，这可能归因于基因座多样化或链球菌种群结构的变化，但受试者体内种群的组成保持相对稳定。 CRISPR 间隔互补体的个体特异性和可追踪特性可能为个性化医疗领域扩展到口腔微生物组开辟道路，其中谱系可以根据健康和其他因素进行追踪。
Viruses may play an important role in the evolution of human microbial communities. Clustered regularly interspaced short palindromic repeats (CRISPRs) provide bacteria and archaea with adaptive immunity to previously encountered viruses. Little is known about CRISPR composition in members of human microbial communities, the relative rate of CRISPR locus change, or how CRISPR loci differ between the microbiota of different individuals. We collected saliva from four periodontally healthy human subjects over an 11- to 17-mo time period and analyzed CRISPR sequences with corresponding streptococcal repeats in order to improve our understanding of the predominant features of oral streptococcal adaptive immune repertoires. We analyzed a total of 6859 CRISPR bearing reads and 427,917 bacterial 16S rRNA gene sequences. We found a core (ranging from 7% to 22%) of shared CRISPR spacers that remained stable over time within each subject, but nearly a third of CRISPR spacers varied between time points. We document high spacer diversity within each subject, suggesting constant addition of new CRISPR spacers. No greater than 2% of CRISPR spacers were shared between subjects, suggesting that each individual was exposed to different virus populations. We detect changes in CRISPR spacer sequence diversity over time that may be attributable to locus diversification or to changes in streptococcal population structure, yet the composition of the populations within subjects remained relatively stable. The individual-specific and traceable character of CRISPR spacer complements could potentially open the way for expansion of the domain of personalized medicine to the oral microbiome, where lineages may be tracked as a function of health and other factors.