Bacteria and archaea are frequently attacked by viruses and other mobile genetic elements and rely on dedicated antiviral defense systems, such as restriction endonucleases and CRISPR, to survive. The enormous diversity of viruses suggests that more types of defense systems exist than are currently known. By systematic defense gene prediction and heterologous reconstitution, here we discover 29 widespread antiviral gene cassettes, collectively present in 32% of all sequenced bacterial and archaeal genomes, that mediate protection against specific bacteriophages. These systems incorporate enzymatic activities not previously implicated in antiviral defense, including RNA editing and retron satellite DNA synthesis. In addition, we computationally predict a diverse set of other putative defense genes that remain to be characterized. These results highlight an immense array of molecular functions that microbes use against viruses.

Host defense mechanisms evolve to alleviate the detrimental effect of parasites. They can be categorized into two components: resistance and tolerance (Råberg et al., 2009). Resistance is the ability of a host to reduce parasite burden, resulting from defense against parasite infection or proliferation early after infection (Schmid-Hempel, 2013). The negative effect of resistance on parasite fitness can lead to antagonistic coevolution. According to theoretical models, fluctuating host and parasite genotypes arise, and