Type IV CRISPR-Cas systems are highly diverse and involved in competition between plasmids

Abstract

CRISPR-Cas systems provide prokaryotes with adaptive immune functions against viruses and other genetic parasites by leveraging small non-coding RNAs for nuclease-dependent degradation of their nucleic acid targets. In contrast to all other types of CRISPR-Cas systems, the mechanisms and biological roles of type IV systems have remained largely overlooked. Here, we describe a previously uncharted diversity of type IV gene cassettes, distributed across diverse prokaryotic genome backgrounds, and propose their classification into subtypes and variants. Congruent with recent findings, type IV modules were primarily found on plasmid-like elements. Remarkably, via a comprehensive analysis of their CRISPR spacer content, these systems were found to exhibit a strong bias towards the targeting of other plasmids. Our data indicate that the functions of type IV systems have diverged from those of other host-related CRISPR-Cas immune systems to adopt a yet unrecognised role in mediating conflicts between plasmids that compete to monopolize their hosts. Furthermore, we find evidence for cross-talk between certain type IV and type I CRISPR-Cas systems that co-exist intracellularly, thus providing an answer to the enigmatic absence of adaptation modules in these systems. Collectively, our results lead to the expansion and reclassification of type IV systems and provide novel insights into the biological function and evolution of these elusive systems.