title: Chromosomal targeting by CRISPR-Cas systems can contribute to genome plasticity in bacteria.
abstract: The clustered regularly interspaced short palindromic repeats (CRISPR) and their associated (Cas) proteins form adaptive immune systems in bacteria to combat phage and other foreign genetic elements. Typically, short spacer sequences are acquired from the invader DNA and incorporated into CRISPR arrays in the bacterial genome. Small RNAs are generated that contain these spacer sequences and enable sequence-specific destruction of the foreign nucleic acids. Occasionally, spacers are acquired from the chromosome, which instead leads to targeting of the host genome. Chromosomal targeting is highly toxic to the bacterium, providing a strong selective pressure for a variety of evolutionary routes that enable host cell survival. Mutations that inactivate the CRISPR-Cas functionality, such as within thecasgenes, CRISPR repeat, protospacer adjacent motifs (PAM), and target sequence, mediate escape from toxicity. This self-targeting might provide some explanation for the incomplete distribution of CRISPR-Cas systems in less than half of sequenced bacterial genomes. More importantly, self-genome targeting can cause large-scale genomic alterations, including remodeling or deletion of pathogenicity islands and other non-mobile chromosomal regions. While control of horizontal gene transfer is perceived as their main function, our recent work illuminates an alternative role of CRISPR-Cas systems in causing host genomic changes and influencing bacterial evolution.
authors.affiliation: Department of Microbiology and Immunology; University of Otago; Dunedin, New Zealand.
authors.forename: Ron L
authors.initials: RL
authors.lastname: Dy
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Pitman
authors.forename: Peter C
authors.initials: PC
authors.lastname: Fineran
keywords: CRISPR; Cas; bacterial evolution; bacteriophages; chromosomal targeting; genomic islands; horizontal gene transfer; integrative and conjugative elements; plasmids