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bioRxiv · 10.64898/2026.02.04.703859

The Structural History of Eukarya

Li, Q.·Daumiller, D.·Bryant, P.
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Abstract

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 phylogeny derived from all-vs-all structural comparisons of 1,542 eukaryotic proteomes, encompassing nearly 300 trillion protein-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 centred on translational machinery. We identify lineage-specific accelerations of structural evolution in species such as birds and ants that are decoupled from proteome expansion, and show that aggregate structural topology provides a quantitative diagnostic of reference proteome quality. Finally, we demonstrate that proteome-wide structural fidelity enables 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: https://she-app.serve.scilifelab.se/

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Li, Q., Daumiller, D., Bryant, P.. 2026-02-06. The Structural History of Eukarya. https://doi.org/10.64898/2026.02.04.703859

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