Adaptation in CRISPR-Cas Systems

Clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated (Cas) proteins constitute an adaptive immune system in prokaryotes. The system preserves memories of prior infections by integrating short segments of foreign DNA, termed spacers, into the CRISPR array in a process termed adaptation. During the past 3 years, significant progress has been made on the genetic requirements and molecular mechanisms of adaptation. Here we review these recent advances, with a focus on the experimental approaches that have been developed, the insights they generated, and a proposed mechanism for self- versus non-self-discrimination during the process of spacer selection. We further describe the regulation of adaptation and the protein players involved in this fascinating process that allows bacteria and archaea to harbor adaptive immunity. Sternberg et al. review how CRISPR-Cas immune systems acquire memory of infections. They discuss recent advances in the field, including methods to detect memorization, features of the process in the different CRISPR-Cas subtypes, structural insights of the memorization machinery, and mechanisms to avoid self-memorization.