Swappable and non-swappable homorepeats in orthologous proteins reflect distinct patterns of evolutionary flexibility

Homorepeats, or polyX regions, are stretches of the same repeated amino acid found in numerous proteins. Though their significance in functional proteins is acknowledged, it remains unclear whether various homorepeats can be interchangeable within related proteins, a concept termed "swappability." This study examines homorepeat overlaps across 695 species' orthologous proteins, identifying swappable and non-swappable cases to explore their evolution and functional consequences.

OrthoMCL provided 17,415,904 orthologous protein pairs, which were analyzed for homorepeats and aligned to find overlaps between these regions. Of the more than 8.7 million orthologous pairs, 99,386 were non-swappable (identical amino acid type) and 5,018 were swappable (different amino acid type). Swappable cases were longer and enriched in acidic residues, while non-swappable showed lineage-specific variations.

The researchers focused on D/E and A/S overlapping homorepeat pairs. PolyD and polyE were frequently swappable, maintaining roles linked to ribosomal biogenesis. In contrast, polyA and polyS exhibited divergent enrichment patterns in their non-swappable forms, indicating distinct functional specializations. This study highlights the interplay between positional conservation and sequence flexibility in homorepeat evolution.

This research was supported by Project PID2024-156408NA-I00 financed by MICIU/AEI/10.13039/501100011033/FEDER, UE, and grants to individual researchers.