title: An updated evolutionary classification of CRISPR-Cas systems.
abstract: 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.
authors.affiliation: National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, Maryland 20894, USA.
authors.forename: Kira S
authors.initials: KS
authors.lastname: Makarova
authors.affiliation: National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, Maryland 20894, USA.
authors.forename: Yuri I
authors.initials: YI
authors.lastname: Wolf
authors.affiliation: Bioinformatics group, Department of Computer Science, University of Freiberg, Georges-Kohler-Allee 106, 79110 Freiberg, Germany.
authors.forename: Omer S
authors.initials: OS
authors.lastname: Alkhnbashi
authors.affiliation: Bioinformatics group, Department of Computer Science, University of Freiberg, Georges-Kohler-Allee 106, 79110 Freiberg, Germany.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Costa
authors.affiliation: Archaea Centre, Department of Biology, Copenhagen University, Ole Maaløes Vej 5, DK2200 Copenhagen N, Denmark.
authors.forename: Shiraz A
authors.initials: SA
authors.lastname: Shah
authors.affiliation: Bioinformatics group, Department of Computer Science, University of Freiberg, Georges-Kohler-Allee 106, 79110 Freiberg, Germany.
authors.forename: Sita J
authors.initials: SJ
authors.lastname: Saunders
authors.affiliation: Department of Food, Bioprocessing and Nutrition Sciences, North Carolina State University, Raleigh, North Carolina 27606, USA.
authors.forename: Rodolphe
authors.initials: R
authors.lastname: Barrangou
authors.affiliation: Laboratory of Microbiology, Wageningen University, Dreijenplein 10, 6703HB Wageningen, Netherlands.
authors.forename: Stan J J
authors.initials: SJ
authors.lastname: Brouns
authors.affiliation: Department of Regulation in Infection Biology, Helmholtz Centre for Infection Research, D-38124 Braunschweig, Germany.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Charpentier
authors.affiliation: National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, Maryland 20894, USA.
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Haft
authors.affiliation: DuPont Nutrition and Health, BP10, Dangé-Saint-Romain 86220, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Horvath
authors.affiliation: Département de Biochimie, de Microbiologie et de Bio-informatique, Faculté des Sciences et de Génie, Groupe de Recherche en Écologie Buccale, Félix d'Hérelle Reference Center for Bacterial Viruses, Faculté de médecine dentaire, Université Laval, Québec City, Québec, Canada.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Moineau
authors.affiliation: Departamento de Fisiología, Genética y Microbiología. Universidad de Alicante. 03080-Alicante, Spain.
authors.forename: Francisco J M
authors.initials: FJ
authors.lastname: Mojica
authors.affiliation: Biochemistry and Molecular Biology, Genetics and Microbiology, University of Georgia, Davison Life Sciences Complex, Green Street, Athens, Georgia 30602, USA.
authors.forename: Rebecca M
authors.initials: RM
authors.lastname: Terns
authors.affiliation: Biochemistry and Molecular Biology, Genetics and Microbiology, University of Georgia, Davison Life Sciences Complex, Green Street, Athens, Georgia 30602, USA.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Terns
authors.affiliation: Biomedical Sciences Research Complex, University of St Andrews, North Haugh, St Andrews, KY16 9TZ, UK.
authors.forename: Malcolm F
authors.initials: MF
authors.lastname: White
authors.affiliation: Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, M5S 3E5, Canada.
authors.forename: Alexander F
authors.initials: AF
authors.lastname: Yakunin
authors.affiliation: Archaea Centre, Department of Biology, Copenhagen University, Ole Maaløes Vej 5, DK2200 Copenhagen N, Denmark.
authors.forename: Roger A
authors.initials: RA
authors.lastname: Garrett
authors.affiliation: Laboratory of Microbiology, Wageningen University, Dreijenplein 10, 6703HB Wageningen, Netherlands.
authors.forename: John
authors.initials: J
authors.lastname: van der Oost
authors.affiliation: Bioinformatics group, Department of Computer Science, University of Freiberg, Georges-Kohler-Allee 106, 79110 Freiberg, Germany.|BIOSS Centre for Biological Signaling Studies, Cluster of Excellence, University of Freiburg, Germany.
authors.forename: Rolf
authors.initials: R
authors.lastname: Backofen
authors.affiliation: National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, Maryland 20894, USA.
authors.forename: Eugene V
authors.initials: EV
authors.lastname: Koonin
mesh_terms: D001105:Archaea / Q000235:genetics*; D001419:Bacteria / Q000235:genetics*; D064113:CRISPR-Cas Systems / Q000235:genetics*; D019143:Evolution, Molecular; D020745:Genome, Archaeal; D016680:Genome, Bacterial; D010802:Phylogeny