Self-targeting by CRISPR: gene regulation or autoimmunity?

Abstract

The recently discovered prokaryotic immune system known as CRISPR (clustered regularly interspaced short palindromic repeats) is based on small RNAs ('spacers') that restrict phage and plasmid infection. It has been hypothesized that CRISPRs can also regulate self gene expression by utilizing spacers that target self genes. By analyzing CRISPRs from 330 organisms we found that one in every 250 spacers is self-targeting, and that such self-targeting occurs in 18% of all CRISPR-bearing organisms. However, complete lack of conservation across species, combined with abundance of degraded repeats near self-targeting spacers, suggests that self-targeting is a form of autoimmunity rather than a regulatory mechanism. We propose that accidental incorporation of self nucleic acids by CRISPR can incur an autoimmune fitness cost, and this could explain the abundance of degraded CRISPR systems across prokaryotes.