Evolutionary history and functional divergence of hydroxycarboxylic acid receptors in primates

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ID: 314955
2026
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Abstract
Hydroxycarboxylic acid receptors are class A G-protein-coupled receptors that act as metabolic sensors linking cellular metabolic status to physiological and immune responses. This family comprises three members (HCAR1, HCAR2, and HCAR3), expressed in metabolically active tissues and immune cells. Here, we investigate the evolutionary history of the most recently derived members, HCAR2 and HCAR3, in primates. Phylogenetic analyses reveal a complex duplicative history involving multiple independent duplication events during ape evolution. As a result, most ape lineages harbor independently originated duplicated copies, whereas non-ape primates retain the ancestral single-copy condition (HCAR2/3). Functional inference indicates that this single-copy gene may be functionally similar to HCAR2, suggesting that the major functional innovation in apes is associated with the emergence of HCAR3. Gene expression analyses further show that major divergence in tissue expression occurred early, following the duplication that generated HCAR1 and the HCAR2/3 lineage, while HCAR2 and HCAR3 retain largely overlapping expression profiles. Together, Our results suggest that HCAR3 receptors may have evolved repeatedly in apes, potentially contributing to refined lipid-sensing.
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openalex_W7162392163 Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Juan C. Opazo, L Felipe Barros, Kattina Zavala, R. Maldonado, Gonzalo A. Mardones
Journal genome biology and evolution
Year 2026
DOI
10.1093/gbe/evag126
URL
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