The Interfaces of Genetic Conflict Are Hot Spots for Innovation

Abstract

RNA-guided Cas9 endonucleases protect bacteria from viral infection and have been creatively repurposed as programmable molecular scalpels for surgical manipulation of DNA. Now, two papers in Cell (Pawluk et al. and Rauch et al.) identify viral proteins that suppress Cas9 and may function like molecular sheaths for the Cas9 scalpel.

Figure. An evolutionary tit-for-tat between host CRISPRs and viral anti-CRISPRs

Schematic representation of a virus infecting a bacterial cell. The cell contains an active type II CRISPR system—typified by Cas9—and a CRISPR locus with a spacer (red) complementary to a target in the viral genome (red). However, in some cases a phage (a virus that infect bacteria) is able to integrate the bacterial genome. The integrated phage is now called a prophage (blue) and the cell is referred to as a lysogen. If the host CRISPR locus contains a spacer (green) that targets the prophage, then this may elicit an autoimmune reaction that results in the degradation of the host genome. Some (pro)phages encode anti-CRISPR (Acr, red arrow) proteins that blocks Cas9 cleavage, preventing CRISPR-induced autoimmunity. In this case, the host and the prophage have a shared interest in preventing Cas9 degradation, but the trade-off is that Acr-mediated blocking of the immune systems also make the cell more susceptible infection by subsequent viruses.