The basic building blocks and evolution of CRISPR–Cas systems

Abstract

CRISPR (clustered regularly interspaced short palindromic repeats)-Cas (CRISPR-associated) is an adaptive immunity system in bacteria and archaea that functions via a distinct self/non-self recognition mechanism that involves unique spacers homologous with viral or plasmid DNA and integrated into the CRISPR loci. Most of the Cas proteins evolve under relaxed purifying selection and some underwent dramatic structural rearrangements during evolution. In many cases, CRISPR-Cas system components are replaced either by homologous or by analogous proteins or domains in some bacterial and archaeal lineages. However, recent advances in comparative sequence analysis, structural studies and experimental data suggest that, despite this remarkable evolutionary plasticity, all CRISPR-Cas systems employ the same architectural and functional principles, and given the conservation of the principal building blocks, share a common ancestry. We review recent advances in the understanding of the evolution and organization of CRISPR-Cas systems. Among other developments, we describe for the first time a group of archaeal cas1 gene homologues that are not associated with CRISPR-Cas loci and are predicted to be involved in functions other than adaptive immunity.