Eukaryotes’ closest relatives are internally simple syntrophic archaea

Abstract Eukaryotes are theorized to have originated from an archaeal phylum Promethearchaeota (formerly ‘Asgard’ archaea) 1,2 . The first cultured representatives revealed valuable insight 3,4 but are distantly related to the first eukaryotic common ancestor (FECA), leaving many unknowns regarding this archaeon’s biology. Here, we report isolation of two strains belonging to the order proposed as FECA’s closest relative, ‘Hodarchaeales’, 5 as members of a pure co- and tri-culture with methanogenic partners. Both are obligately anaerobic, syntrophic, peptide-degrading, and mesophilic archaea that have simple internal cell structure and produce protrusions and vesicles, like Promethearchaeales 3,4 . All strains demonstrate behavior focused on cell construction rather than division, unlike typical prokaryotes 6 . Strain HC1 possesses genes associated with aerobic lifestyles but lacks complete pathways for aerobic respiration and co-cultures cannot grow under (micro)aerobic conditions, suggesting the genes support oxygen detoxification rather than respiration. Reflecting this, HC1 can survive and grow under microaerobic conditions only when aerobic organisms are present. Phylogenetic analyses indicate FECA may have possessed these genes and thus some aerotolerance. Physiological, genomic, and phylogenetic observations indicate FECA was a simple-celled anaerobic syntrophic peptide-degrading archaeon with a non-growth-centric lifestyle and potential adaptations towards an oxygenated planet—the archaea-eukaryote transition was steep in both cell structure and aerobiosis.