Structure-Powered Expansion of Eukaryote-Like Toolkit in Asgard Archaea

A large-scale structural analysis of 936 Asgard archaeal genomes using ColabFold and protein language models identified 1,319 novel isomorphic ESPs (iESPs) and organized them into 908 structural clusters, greatly expanding the repertoire of eukaryotic-like proteins in Asgard archaea. The iESPs are enriched in information storage/processing and cellular signaling, including components related to the vault (MVP) and Commander (COMMD) complexes, suggesting a higher degree of eukaryote-like cellular complexity in the archaeal ancestor of eukaryotes. The study also reveals patchy distributions and emphasizes that structural similarity, not just sequence similarity, drives annotation, highlighting the value of structure-based approaches for tracing deep evolutionary connections. The findings support a more nuanced view of eukaryogenesis and provide a methodological blueprint for uncovering distant homologues in non-model organisms.