Gene-culture coevolution shapes olfactory receptor gene diversity in Orang Asli populations

The genetic and evolutionary basis of human olfaction remains understudied. We examined olfactory receptor (OR) gene evolution in Malaysian Orang Asli with distinct subsistence modes: Negrito hunter-gatherers, Senoi swidden-agriculturalists, and Jakun horticulturalists. Global populations generally display elevated OR diversity relative to genome-wide levels, whereas Negritos exhibit conserved OR gene profiles featured by lower mutation load, accelerated ancestral allele retention, and depleted archaic introgression. Subsistence-related divergence revealed adaptive signals at the ancestral haplotypes in OR12D2 (geosmin) and OR52J3-OR52E2 (butter) and enriched archaic introgression in musk/fruity receptors (e.g., OR5A1/2 and OR4D6) in Negritos, whereas agriculturalists showed diversification involving pleiotropic targets, including OR12D3 (insulin regulation) and receptors tied to lung function. These findings suggest that directional selections preserve ancestral olfactory repertoires in hunter-gatherers, while agricultural transitions drive diversification through direct chemosensory adaptation and indirect pleiotropic pressures. Our analysis demonstrated how subsistence strategies shape sensory evolution via intertwined genetic, cultural, and environmental pathways.