Whole-genome sequences provide insights into the formation and adaptation of human populations in the Himalayas

Abstract

High-altitude environments pose significant challenges to human survival and reproduction, drawing considerable attention to the demographic and adaptive histories of populations in these regions. Here, we present whole-genome sequences from diverse Himalayan populations, offering new insights into the genomic history of this region. We find that population structure in the Himalayas began as early as 10,000 years ago, predating archaeological evidence of permanent habitation above 2,500 meters by ~6,000 years. The widespread presence of the introgressed adaptive EPAS1 haplotype across all high-altitude populations highlights a shared genetic origin and its importance for survival in this region. We identify additional selection signals in genes linked to hypoxia, physical activity, immunity, and metabolism, all of which could have facilitated adaptation to the harsh environment. Over time, increasing genetic structure led to the emergence of the strongly differentiated ethnic groups observed today, many of which maintained small effective population sizes throughout their history or experienced severe bottlenecks. Between 6,000 and 3,000 years ago, with the advent of agriculture, a few uniparental lineages became predominant; however, significant population growth was not observed in the Himalayas except in the Tibetans. In recent history, we detect bidirectional gene flow between high-altitude and lowland groups on both sides of the Himalayan range, coinciding with the rise and expansion of historical regional powers, particularly during the Tibetan and northern Indian Gupta Empires. In the past few centuries, migrations to the Himalayas seem to have occurred alongside conflicts and population displacements in nearby regions and show some sex bias.