Malaria resistance-related biological adaptation and complex evolutionary footprints of Tai-Kadai people inferred from 796 genomes

ABSTRACT Pathogen-host adaptative interaction and complex population demographical processes, including admixture, drift and Darwen selection, have considerably shaped the Neolithic-to-Modern Western Eurasian population structure and genetic susceptibility to modern human diseases. However, the genetic footprints of evolutionary events in East Asia keep unknown as the underrepresentation of genomic diversity and the design of large-scale population studies. We reported one aggregated database of genome-wide-SNP variations from 796 Tai-Kadai (TK) genomes, including Bouyei first reported here, to explore the genetic history, population structure and biological adaptative features of TK-speaking people from Southern China and Southeast Asia. We found geography-related population substructure among TK-speaking people using the state-of-the-art population genetic structure reconstruction techniques based on the allele frequency spectrum and haplotype-resolved phased fragments. We found that the Northern TK-speaking people from Guizhou harboured one TK-dominant ancestry maximised in Bouyei people, and the Southern one from Thailand obtained more influences from Southeast Asians and indigenous people. We reconstructed the fitted admixture models and demographic graphs, which showed that TK-speaking people received gene flow from ancient rice farmer-related lineages related to the Hmong-Mien and Austroasiatic people and Northern millet farmers associated with the Sino-Tibetan people. Biological adaptation focused on our identified unique TK lineages related to Bouyei showed many adaptive signatures conferring Malaria resistance and low-rate lipid metabolism. Further gene enrichment, the allele frequency distribution of derived alleles, and their correlation with the incidence of Malaria further confirmed that CR1 played an essential role in the resistance of Malaria in the ancient “Baiyue” tribes.