The structural history of Eukarya

Comparative genomics has traditionally relied on sequence-based markers, yet the global evolutionary landscape of protein architecture remains largely unexplored. We present the Structural History of Eukarya (SHE), a structural similarity-derived phylogeny from all-vs-all structural comparisons on the proteome level of 1542 eukaryotic species, encompassing nearly 300 trillion pairwise protein alignments. This proteome-scale analysis reveals a bipartite model of eukaryotic evolution: a rigid Strict Core dominated by cytoskeletal architecture, supporting a more plastic Operational Engine centered on translational machinery. We identify lineage-specific accelerations of structural evolution in species such as birds and ants that are decoupled from proteome expansion. Finally, we demonstrate that proteome-wide structural fidelity enables the functional annotation of uncharacterized proteins and a data-driven framework for model organism selection, replacing heuristic choices with quantitative matching to human biological processes. SHE is freely accessible as an interactive portal.