Stephan Köstlbacher, PhD, AITHYRA, Research Institute for Biomedical Artificial Intelligence, Vienna, Austria will give a talk on:

"Lost in sequence, found in fold: structural traces of eukaryotic complexity in Asgard archaea"

Thursday, 28 May 2026

3 p.m.

Seminar room 3.1, UBB, Djerassiplatz 1, 1030 Vienna, University of Vienna

Join us!

The eukaryotic cell arose from a symbiosis between an Asgard archaeon and at least one bacterial partner. Yet the cellular complexity of that archaeal ancestor sits across one of the longest branches in the tree of life, where roughly two billion years of divergence have driven much of its protein repertoire past the reach of sequence-based homology detection. To see beyond that limit, we built a pangenome-scale structural catalogue of Asgard archaea, combining sensitive sequence searches with de novo structure prediction and structural similarity. On this catalogue we define isomorphic ESPs (iESPs): Asgard archaeal proteins whose closest structural matches show statistically significant enrichment for eukaryotic homologues, even when sequence similarity has eroded. This approach more than triples the set of Asgard archaeal eukaryotic signature proteins and recovers several unexpected components: the first archaeal homologues of the eukaryotic Vault complex (MVP), previously reported only in a few bacteria; the Commander complex (COMMD), for which no prokaryotic homologues had been described; Ufm1 and CINP, so far uniquely shared between Asgard archaea and eukaryotes; and a substantial set of metabolic proteins, contrasting with the prevailing view of a predominantly bacterial origin for eukaryotic metabolism. Together, these results point to an archaeal ancestor of eukaryotes that was substantially more eukaryote-like than current models assume, and illustrate how AI-based structural modelling is beginning to reshape what we can read from the deepest branches of the tree of life.