Tera Levin

Our new article, “The Prokaryotic Roots of Eukaryotic Immune Systems,” is out. Immune factors from both prokaryotes (e.g., restriction-modification, CRISPR/Cas systems) and eukaryotes (antibodies) have been central reagents for the very emergence of modern biochemistry and molecular biology. But this historical course superficially indicated that the immune systems of prokaryotes and eukaryotes might have little in common. However, starting from our early work on domains involved in eukaryotic apoptosis in the late 1990s, it started becoming increasingly clear to us that there were deep evolutionary connections between eukaryotic and prokaryotic immune systems despite the extreme divergence that is a natural feature of them. These connections take multiple forms: 1. Direct homologies, where immune components were either vertically inherited or laterally transferred from the prokaryotic superkingdoms. This group includes the growing body of evidence regarding domains at the interface of immunity and apoptosis; 2. Then there are homologous domains that were drawn from different prokaryotic conflict systems e.g., those involved in interorganismal conflict and incorporated into eukaryotic immunity – e.g., the mutagenic AID/APOBEC -like deaminases. 3. Finally, there are the analogs that have convergently acquired comparable immune functions in the different superkingdoms. Together they make up a tangled tale of immunity of which we provide a brief account here. You will find little sketches of many domains of interest to the connoisseur and first-time explorer alike: SMODS and friends, TIR, Sirtuin, ADP-ribosyltransferase fold, Schlafen, base deaminases, viperins, caspases, FGS, ricin, GTPases, STANDs, TRADD-N, the Death-like fold and more. doi.org/10.1146/annurev-gene…