How far can you borrow? Divergence limits of cross-species Gene Ontology enrichment in non-model organisms.

Cross-species Gene Ontology transfer enrichment across six non-model eukaryotes shows set-level fidelity declines monotonically with phylogenetic distance, reaching chance at clade boundaries in some panels (ID50 ~40%-59%).

• Why it matters: Practitioners borrow GO from distant models for enrichment on inferred orthologs, but the divergence threshold where results degrade has not been quantified for real analysis choices.
• What they did: They benchmarked GO-transfer enrichment using six focal species with 15–22 reference species each, spanning a continuous phylogenetic gradient, and measured set-level fidelity via redundancy-robust Wang semantic similarity.
• The result: Conserved processes transfer reliably while taxon-specific ones do not; richer reference sets increase recall but reduce precision, and whole-genome duplication degrades transfer only under high ohnolog retention, enabling a distance reliability guide and decision protocol.

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