An updated evolutionary classification of CRISPR–Cas systems

The evolution of CRISPR–cas loci, which encode adaptive immune systems in archaea and bacteria, involves rapid changes, in particular numerous rearrangements of the locus architecture and horizontal transfer of complete loci or individual modules. These dynamics complicate straightforward phylogenetic classification, but here we present an approach combining the analysis of signature protein families and features of the architecture of cas loci that unambiguously partitions most CRISPR–cas loci into distinct classes, types and subtypes. The new classification retains the overall structure of the previous version but is expanded to now encompass two classes, five types and 16 subtypes. The relative stability of the classification suggests that the most prevalent variants of CRISPR–Cas systems are already known. However, the existence of rare, currently unclassifiable variants implies that additional types and subtypes remain to be characterized.

K.S.M., Y.I.W., D.H. and E.V.K. are supported by the National Institutes of Health (NIH) Intramural Research Program at the National Library of Medicine, US Department of Health and Human Services. R.M.T. and M.P.T. are supported by NIH grants RO1 GM54682 and RO1 GM99876. J.v.d.O. was partly supported by SIAM Gravitation Grant 024.002.002 from the Netherlands Organization for Scientific Research (N.W.O.). S.J.J.B. was financially supported by an NWO Vidi grant (864.11.005) and European Research Council (ERC) Stg (639707). A.F.Y. is supported by the Natural Sciences and Engineering Research Council (NSERC) Strategic Network Grant IBN and NSERC Discovery grant. S.M. acknowledges funding from Natural Sciences and Engineering Research Council of Canada (Discovery program) and holds a Tier 1 Canada Research Chair in Bacteriophages. F.J.M.M. is supported by the Ministerio de Economía y Competitividad (BIO2014‑53029). R.B. is supported by the Deutsche Forschungsgemeinschaft (DFG) grant (BA 2168/5‑2). S.A.S. and R.A.G. were funded primarily by the Danish Natural Science Research Council.