Imprecise Spacer Acquisition Generates CRISPR-Cas Immune Diversity through Primed Adaptation

• Published in: Cell host & microbe 2019-02, Vol.25 (2), p.250-260.e4
• Main Authors: Jackson, Simon A., Birkholz, Nils, Malone, Lucía M., Fineran, Peter C.
• Format: Article
• Language: English
• Subjects: adaptation; coevolution; CRISPR-Cas; diversity; phage; primed; priming; slipping; spacer acquisition
• ISSN: 1931-3128; 1934-6069
• DOI: 10.1016/j.chom.2018.12.014

Many prokaryotes possess CRISPR-Cas adaptive immune systems to defend against viruses and invading mobile genetic elements. CRISPR-Cas immunity relies on genetic memories, termed spacers, for sequence-specific recognition of infections. The diversity of spacers within host populations is important for immune resilience, but we have limited understanding of how CRISPR diversity is generated. Type I CRISPR-Cas systems use existing spacers to enhance the acquisition of new spacers through primed CRISPR adaptation (priming). Here, we present a pathway to priming that is stimulated by imprecisely acquired (slipped) spacers. Slipped spacers are less effective for immunity but increase priming compared with canonical spacers. The benefits of slipping depend on the relative rates of phage mutation and adaptation during defense. We propose that slipped spacers provide a route to increase population-level spacer diversity that pre-empts phage escape mutant proliferation and that the trade-off between adaptation and immunity is important in diverse CRISPR-Cas systems. [Display omitted] •Imprecisely acquired (slipped) spacers are impaired for CRISPR-Cas immunity•−1 and +1 slipped spacers stimulate primed CRISPR adaptation•Slipped spacers enhance priming before phage escape mutations arise•Slipping enhances CRISPR-Cas resilience to phage mutation by increasing immune diversity CRISPR-Cas prokaryotic immune systems acquire genetic memories, termed spacers, to facilitate defense against phages and mobile genetic elements. Jackson et al. (2018) discover that imprecisely acquired (slipped) spacers are less effective for defense but enhance the acquisition of new spacers, which pre-emptively increases immune diversity before phage escape mutants arise.