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Evolution and classification of the CRISPR–Cas systems

Nature Reviews Microbiology volume 9, pages 467477 (2011) | Download Citation

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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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).

Author information

Affiliations

  1. Kira S. Makarova, Yuri I. Wolf & Eugene V. Koonin are at the National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, 8600 Rockville Pike, Bethesda, Maryland 20894, USA.

    • Kira S. Makarova
    • , Yuri I. Wolf
    •  & Eugene V. Koonin
  2. Daniel H. Haft is at The J. Craig Venter Institute, 9704 Medical Center Drive, Rockville, Maryland 20850, USA.

    • Daniel H. Haft
  3. Rodolphe Barrangou is at Danisco USA Inc., 3329 Agriculture Drive, Madison, Wisconsin 53716, USA.

    • Rodolphe Barrangou
  4. Stan J. J. Brouns and John van der Oost are at the Laboratory of Microbiology, Wageningen University, Dreijenplein 10, 6703 HB Wageningen, The Netherlands.

    • Stan J. J. Brouns
    •  & John van der Oost
  5. Emmanuelle Charpentier is at the Laboratory for Molecular Infection Medicine Sweden, Umeå Centre for Microbial Research, Department of Molecular Biology, Umeå University, S-90187 Umeå, Sweden.

    • Emmanuelle Charpentier
  6. Philippe Horvath is at Danisco France SAS, BP10, 86220 Dangé-Saint-Romain, France.

    • Philippe Horvath
  7. Sylvain Moineau is at the Département de Biochimie, Microbiologie et Bio-informatique, Faculté des Sciences et de Génie, Université Laval, Quebec City, Quebec G1V 0A6, Canada.

    • Sylvain Moineau
  8. Francisco J. M. Mojica is at the Departamento de Fisiología, Genética y Microbiología, Universidad de Alicante, 03080-Alicante, Spain.

    • Francisco J. M. Mojica
  9. Alexander F. Yakunin is at the Banting and Best Department of Medical Research, University of Toronto, Toronto, Ontario M5G 1L6, Canada.

    • Alexander F. Yakunin

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Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Eugene V. Koonin.

Supplementary information

Excel files

  1. 1.

    Supplementary information S1 (table)

PDF files

  1. 1.

    Supplementary information S2 (figure)

  2. 2.

    Supplementary information S4 (table)

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

Word documents

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    Supplementary information S3 (box)

    The phylogenetic tree for Cas1/COG1518 proteins.

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DOI

https://doi.org/10.1038/nrmicro2577

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