Beyond single-trait analysis: ancient genomes reveal coordinated evolution of dietary endophenotypes in Holocene Europe

Diet has been a major selective force throughout human evolution, yet dietary adaptation is often studied through individual loci rather than as interconnected systems of traits. Here, we integrated genome-wide association data for 58 diet-related phenotypes with genomes from 938 ancient Europeans spanning the last 10,000 years to reconstruct the evolution of dietary endophenotypes. We identified four major systems encompassing adiposity and metabolism, body composition, fatty-acid metabolism and food-related behaviours. Multiple endophenotypes showed significant temporal shifts during the Holocene departing from the expected under neutrality, including coordinated decreases in genetic architectures associated with adiposity, insulin regulation and lipid metabolism, alongside increases in traits related to docosahexaenoic acid metabolism. Moreover, these patterns showed marked geographic heterogeneity across Europe. Our results indicate that dietary adaptation proceeded through coordinated evolutionary changes across interconnected physiological systems, providing a systems-level perspective on how cultural and subsistence transitions reshaped human biology.