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Natural CRISPR Systems and Targets in the Human Microbiome

89 Pages Posted: 24 Jun 2020 Publication Status: Published

See all articles by Philipp C. Münch

Philipp C. Münch

Harvard University - Department of Biostatistics

Eric A. Franzosa

Harvard University - Department of Biostatistics

Bärbel Stecher

Ludwig Maximilian University of Munich (LMU) - Max von Pettenkofer-Institute

Alice C. McHardy

Helmholtz Center for Infection Research - Department for Computational Biology of Infection Research

Curtis Huttenhower

Harvard University - Department of Biostatistics

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Abstract

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 provides a new window into their diversity. We profiled CRISPR loci and cas genes in the body-wide human microbiome using 2,355 metagenomes spanning 265 individuals, yielding functional and taxonomic profiles for 2.9 million spacers. Spacer and repeat profiles agreed qualitatively with those from isolate genomes but expanded their diversity by approximately 20-fold, with the highest spacer load present in the oral microbiome. Taxonomy of spacer carriage paralleled that of the communities in which they were contained, with functional targets enriched for viral elements but also including other microbial structural and enzymatic elements. When coupled with cas gene systems, CRISPR–Cas subtypes were highly site- and taxon-specific. Our analysis provides the first comprehensive collection of natural CRISPR–cas loci and targets in the human microbiome.

Keywords: CRISPR, cas genes, human host, metagenome, phage defense, bacterial defense mechanisms, bacteriophages, restriction modification system

Suggested Citation

Münch, Philipp C. and Franzosa, Eric A. and Stecher, Bärbel and McHardy, Alice C. and Huttenhower, Curtis, Natural CRISPR Systems and Targets in the Human Microbiome. Available at SSRN: https://ssrn.com/abstract=3617187 or http://dx.doi.org/10.2139/ssrn.3617187
This version of the paper has not been formally peer reviewed.

Philipp C. Münch

Harvard University - Department of Biostatistics ( email )

Boston, MA
United States

Eric A. Franzosa

Harvard University - Department of Biostatistics ( email )

Boston, MA
United States

Bärbel Stecher

Ludwig Maximilian University of Munich (LMU) - Max von Pettenkofer-Institute

Pettenkoferstraße 9A
München, 80336
Germany

Alice C. McHardy

Helmholtz Center for Infection Research - Department for Computational Biology of Infection Research ( email )

Curtis Huttenhower (Contact Author)

Harvard University - Department of Biostatistics ( email )

Boston, MA
United States

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