Lien vers Pubmed [PMID] – 39208803
Lien vers HAL – hal-04735152
Lien DOI – 10.1016/j.chom.2024.08.002
Cell Host & Microbe, 2024, 32 (9), pp.1594-1607.e5. ⟨10.1016/j.chom.2024.08.002⟩
Deciphering the immune organization of eukaryotes is of importance for human health and for the understanding of ecosystems. The recent discovery of dozens novel antiphage systems revealed that various eukaryotic immune proteins originate from prokaryotic antiphage systems. Whether antiphage proteins of bacteria can be utilized to discover immune proteins in eukaryotes remains unexplored. Here, we use a phylogenydriven approach to uncover novel eukaryotic immune proteins by searching for homologs of bacterial antiphage systems. We demonstrate that proteins displaying sequence similarity with recently discovered antiphage systems are widespread in eukaryotes, and maintain a role in immunity in humans. Two eukaryotic proteins of the anti-transposon piRNA pathway are evolutionary linked to the antiphage system Mokosh. We uncover and experimentally validate human antiviral genes which are related to the Eleos and Lamassu prokaryotic systems. Our work illustrates how comparative genomics of immune mechanisms can be employed to uncover defence genes in eukaryotes.