Archaic introgression contributed to the pre-agriculture adaptation of vitamin B1 metabolism in East Asia.

Thiamine (vitamin B1) is an essential micronutrient. Genes involved in thiamine metabolisms, such as , , and , were assumed to be underlying positive selection in East Asians, but the detailed mechanism remains unknown. Here, we analyzed genome data of 3,823 individuals representing 223 global populations and identified the adaptive haplotypes at thiamine genes. Interestingly, the putative adaptive haplotype at was of Neanderthal ancestry, while that at was also likely of archaic origins. Leveraging new methods and available ancient DNA data, we further demonstrated that the beneficial haplotypes reached a high frequency at least 10,000 years ago and are maintained persistently in present-day East Asians. We argue that pathogens, rather than agriculture developed ∼10,000 years ago in East Asia, were likely the initial driving force of the putative positive selection. Notably, the first American people did not carry the putative adaptive haplotype at .