CONICET | Buscador de Institutos y Recursos Humanos

Sex-like genomic exchangehas been described for evolutionary distant archaeal species. Although thesegene transfer events point to the existence of cell-cell fusion in this domainof life no molecular or cellular actors have been identified so far. Ineukaryotes, sexual reproduction is ancestral and relies on HAP2(GCS1), a plasmamembrane protein that is necessary and sufficient to fuse gametes. Structuraland phylogenetic analysis demonstrates that HAP2 shares common ancestry withtwo apparently unrelated proteins: class II viral fusogens that catalyze membranefusion between enveloped viruses and host cells and FF proteins, which mediatesomatic cell-cell fusion during nematode development. We named this superfamilyFusexins: fusion proteins essential for sexual reproduction and exoplasmicmerger of plasma membranes. Fusexins present an intriguing evolutionary historythat trigger questions like: are these fusion proteins viral inventionscaptured by early eukaryotes to enable sexual reproduction or were theycaptured by the viruses from ancient hosts? Here we present evidence indicatingthat fusexins were an archaeal innovation. Using a comprehensivesearch strategy, based on highly sensitive similarity/homology search tools (PSI-BLAST,HMMER and HHpred) coupled with structural prediction algorithms, we were ableto identify fusexins in distantly related archaeal genomes. We selected ten candidate genes to determinewhether they are sufficient to fuse archaeal or eukaryotic cells. Some fusexinswere expressed in mammalian cells and induced multinucleation suggesting thatthey are indeed active in cell fusion. Structural, cellular and geneticcharacterization of archaeal fusexins is currently underway. Our hypothesis isthat fusexins originated in ancestral archaea to mediate sexual cell-cellfusion, later incorporated by unicellular protists for mating and finally,adopted by animals for fusion of somatic cells.