An updated evolutionary classification of CRISPR–Cas systems

Key Points CRISPR–Cas systems provide archaea and bacteria with adaptive immunity against viruses and plasmids. CRISPR–Cas genomic loci show extreme diversity in sequence and gene arrangement. We developed a computational approach for CRISPR–Cas classification, combining comparisons of Cas protein sequences and locus architectures. Two classes, five types and 16 subtypes of CRISPR–Cas systems were identified based on this approach. An automated classifier was developed for assigning CRISPR–Cas loci from sequenced genomes to specific subtypes. The evolution of CRISPR–Cas systems is marked by extensive horizontal transfer and recombination of functional modules. CRISPR–Cas systems provide bacteria and archaea with adaptive immunity to invading foreign DNA. In an Analysis article, Koonin and colleagues update a previous classification of these systems to incorporate the large volume of genomic data generated in recent years. 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.