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Evolution and classification of the CRISPR–Cas systems

Abstract

The CRISPR–Cas (clustered regularly interspaced short palindromic repeats–CRISPR-associated proteins) modules are adaptive immunity systems that are present in many archaea and bacteria. These defence systems are encoded by operons that have an extraordinarily diverse architecture and a high rate of evolution for both the cas genes and the unique spacer content. Here, we provide an updated analysis of the evolutionary relationships between CRISPR–Cas systems and Cas proteins. Three major types of CRISPR–Cas system are delineated, with a further division into several subtypes and a few chimeric variants. Given the complexity of the genomic architectures and the extremely dynamic evolution of the CRISPR–Cas systems, a unified classification of these systems should be based on multiple criteria. Accordingly, we propose a 'polythetic' classification that integrates the phylogenies of the most common cas genes, the sequence and organization of the CRISPR repeats and the architecture of the CRISPR–cas loci.

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Figure 1: The three stages of CRISPR–Cas action.
Figure 2: The relationship of the three major types and ten subtypes of CRISPR systems.
Figure 3: Phylogenetic tree for Cas1 (COG1518) proteins.

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Acknowledgements

The authors thank M. Terns for critical reading of the manuscript and useful discussions. K.S.M., Y.I.W. and E.V.K. are supported by the intramural funds of the US Department of Health and Human Services (National Library of Medicine); D.H.H. is supported by a US National Institutes of Health grant (1 R01 HG004881); E.C. acknowledges funding from Umeå University, Sweden, and the Swedish Research Council. S.M. acknowledges funding from the National Sciences and Engineering Research Council of Canada (the Discovery programme); F.J.M.M. acknowledges support from the University of Alicante, Spain, (Vicerrectorado de Investigacion, and Desarrollo e Innovacion) for the use of its research technical services; A.F.Y. is supported by the Government of Canada through Genome Canada and the Ontario Genomics Institute (grant 2009-OGI-ABC-1405). S.J.B. and J.O. are supported by Veni and TOP grants from the Netherlands Organization for Scientific Research (NWO).

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Correspondence to Eugene V. Koonin.

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Supplementary information

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Supplementary information S2 (figure)

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Supplementary information S3 (box)

The phylogenetic tree for Cas1/COG1518 proteins. (DOC 153 kb)

Supplementary information S4 (table)

Classification and nomenclature of CRISPR-associated genes* (updated TIGRFAMs profile identifiers included) (PDF 255 kb)

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Makarova, K., Haft, D., Barrangou, R. et al. Evolution and classification of the CRISPR–Cas systems. Nat Rev Microbiol 9, 467–477 (2011). https://doi.org/10.1038/nrmicro2577

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