Department of Biostatistics, Harvard School of Public Health, Boston, MA 02115, USA; Department for Computational Biology of Infection Research, Helmholtz Center for Infection Research, 38124 Braunschweig, Germany; Max von Pettenkofer-Institute for Hygiene and Clinical Microbiology, Ludwig-Maximilian University of Munich, 80336 Munich, Germany.
Department of Biostatistics, Harvard School of Public Health, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Cell Host Microbe. 2021 Jan 13;29(1):94-106.e4. doi: 10.1016/j.chom.2020.10.010. Epub 2020 Nov 19.
Many bacteria resist invasive DNA by incorporating sequences into CRISPR loci, which enable sequence-specific degradation. CRISPR systems have been well studied from isolate genomes, but culture-independent metagenomics provide a new window into their diversity. We profiled CRISPR loci and cas genes in the body-wide human microbiome using 2,355 metagenomes, yielding functional and taxonomic profiles for 2.9 million spacers by aligning the spacer content to each sample's metagenome and corresponding gene families. Spacer and repeat profiles agree qualitatively with those from isolate genomes but expand their diversity by approximately 13-fold, with the highest spacer load present in the oral microbiome. The taxonomy of spacer sequences parallels that of their source community, with functional targets enriched for viral elements. When coupled with cas gene systems, CRISPR-Cas subtypes are highly site and taxon specific. Our analysis provides a comprehensive collection of natural CRISPR-cas loci and targets in the human microbiome.
许多细菌通过将序列整合到 CRISPR 基因座中来抵抗入侵的 DNA，从而实现序列特异性降解。CRISPR 系统已经从分离基因组中得到了很好的研究，但非培养的宏基因组学为它们的多样性提供了一个新的视角。我们使用 2355 个宏基因组对人体微生物组的全身 CRISPR 基因座和 cas 基因进行了分析，通过将间隔物内容与每个样本的宏基因组和相应的基因家族进行比对，为 290 万个间隔物生成了功能和分类学特征。间隔物和重复序列的特征与从分离基因组中获得的特征基本一致，但它们的多样性扩展了约 13 倍，口腔微生物组中的间隔物负荷最高。间隔序列的分类与它们的来源群落的分类一致，功能靶标富集了病毒元件。当与 cas 基因系统结合使用时，CRISPR-Cas 亚型在靶位和分类上具有高度特异性。我们的分析提供了人类微生物组中天然 CRISPR-cas 基因座和靶标的综合集合。
