Archaeal origins of gamete fusion

Sexual reproduction in Eukarya consists of genome reduction by meiosis and subsequent gamete fusion. The presence of meiotic genes in Archaea and Bacteria suggests that prokaryotic DNA repair mechanisms evolved towards meiotic recombination. However, the evolutionary origin of gamete fusion is less clear because fusogenic proteins resembling those found in Eukarya have so far not been identified in prokaryotes. Here, using bioinformatics, we identified archaeal genes encoding candidates of fusexins, a superfamily of fusogens mediating somatic and gamete fusion in multiple eukaryotic lineages. Crystallographic structure determination of a candidate archaeal FusexinA reveals an archetypical trimeric fusexin architecture with novel features such as a six-helix bundle and an additional globular domain. We demonstrate that ectopically expressed FusexinA can fuse mammalian cells, and that this process involves the additional domain and a more broadly conserved fusion loop. Genome content analyses reveal that archaeal fusexins genes are within integrated mobile elements. Finally, evolutionary analyses place these archaeal fusogens as the founders of the fusexin superfamily. Based on these findings, we propose a new hypothesis on the origins of eukaryotic sex where an archaeal fusexin, originally used by selfish elements for horizontal transmission, was repurposed to enable gamete fusion.