Oxygen-adaptive plasticity of Asgard archaea dependent on terminal oxidase and globin

The oxygenation of ancient Earth is thought to have driven eukaryogenesis, beginning with the endosymbiosis of an aerobic alphaproteobacterium (proto-mitochondria) with an archaeal host. Given that the archaeal host likely evolved from within Asgard archaea (phylum Promethearchaeota), the metabolic traits of Asgard archaea could provide key insights into eukaryotic origins. Although Asgard archaea cultured to date are obligate anaerobes, their genomes encode oxygen-adaptive proteins, suggesting they might be oxygen-tolerant. Here, we demonstrate that some Asgard archaea, in particular, Hodarchaeales, the closest known relatives of eukaryotes, and Kariarchaeaceae, exhibit oxygen adaptation mediated by terminal oxidase and globin. Phylogenetic analysis reveals long-term vertical evolution of terminal oxidases in Asgard archaea, suggesting ancient adaptation to molecular oxygen. By contrast, globin was likely acquired by Asgard archaea via horizontal gene transfer from facultative aerobic Chloroflexales bacteria. Heterologous expression of the Asgard globin enhances aerobic growth of Haloarchaea and Escherichia coli in the presence of terminal oxidase-dependent electron transfer chain, suggesting that Asgard growth benefits from ambient oxygen. The Asgard globin gene is embedded in an oxygen-sensitive bidirectional promoter region, with one promoter driving oxygen-induced globin expression, and the other anaerobically activating expression of two enzymes, PdxS and PdxT, involved in a pyridoxal 5-phosphate biosynthesis. The Asgard globin and promoter region exhibit high functional robustness across archaea and bacteria, and could contribute to the symbiosis between the Asgard and aerobic bacterial partners. These findings highlight the oxygen-adaptive plasticity of Asgard archaea and its potential contribution to eukaryogenesis.