Genetic diversity and differentiated adaptive strategies for underrepresented populations at the crossroad of Southeast and East Asia

The underrepresentation of populations and limited genomic diversity in Southwest China have hindered understanding of human genetic origins and the evolutionary history of health and disease. Yunnan, a biodiversity hotspot at the intersection of Southeast Asia, the Yunnan-Guizhou Plateau, and the Tibetan Plateau, is home to 25 ethnic groups, 15 of which are unique to the region. The absence of genomic data from Yunnan has constrained insights into demographic histories and biological adaptations, posing challenges to precision medicine and health equity. To fill this gap, we conducted genomic analyses of 13 ethnic groups across five language families and nine regions, integrating these data with modern and ancient Eurasian populations to create a comprehensive dataset of Yunnan populations. Our results revealed significant genetic diversity and language-associated substructures within Yunnan populations. Demographic modeling indicated recent and complex ancient admixture events among ethnolinguistically diverse Yunnan populations. Both recent admixture and culturally specific marriage customs have jointly shaped their genetic composition, with distinct marital practices contributing to the unique genetic architectures of the Miao and Lahu. We also uncovered distinct adaptive patterns across Yunnan populations, including positive selection in lipid-metabolism genes in the Miao, immune-related adaptations in the Hani and Austroasiatic groups, and bitter-taste-perception adaptations in the Wa and Blang populations, driven by cultural preferences for bitter foods. This study deepens understanding of the evolutionary history and biological adaptations of Yunnan populations, while contributing to the development of regional precision medicine approaches and to enhancing health equity in underrepresented communities.