Abstract

Abstract Dozens of new antiviral systems have been recently characterized in bacteria. Some of these systems are present in eukaryotes and appear to have originated in prokaryotes, but little is known about these defense mechanisms in archaea. Here, we explore the diversity and distribution of defense systems in archaea and identify 2610 complete systems in Asgardarchaeota , a group of archaea related to eukaryotes. The Asgard defense systems comprise 89 unique systems, including argonaute, NLR, Mokosh, viperin, Lassamu, and CBASS. Asgard viperin and argonaute proteins have structural homology to eukaryotic proteins, and phylogenetic analyses suggest that eukaryotic viperin proteins were derived from Asgard viperins. We show that Asgard viperins display anti-phage activity when heterologously expressed in bacteria. Eukaryotic and bacterial argonaute proteins appear to have originated in Asgardarchaeota , and Asgard argonaute proteins have argonaute-PIWI domains, key components of eukaryotic RNA interference systems. Our results support that Asgardarchaeota played important roles in the origin of antiviral defense systems in eukaryotes.