Long-term genetic stability and a high-altitude East Asian origin for the peoples of the high valleys of the Himalayan arc

Long-term genetic stability and a high-altitude East Asian origin for the peoples of the high valleys of the Himalayan arc

Abstract

The high-altitude transverse valleys [>3,000 m above sea level (masl)] of the Himalayan arc from Arunachal Pradesh to Ladahk were among the last habitable places permanently colonized by prehistoric humans due to the challenges of resource scarcity, cold stress, and hypoxia. The modern populations of these valleys, who share cultural and linguistic affinities with peoples found today on the Tibetan plateau, are commonly assumed to be the descendants of the earliest inhabitants of the Himalayan arc. However, this assumption has been challenged by archaeological and osteological evidence suggesting that these valleys may have been originally populated from areas other than the Tibetan plateau, including those at low elevation. To investigate the peopling and early population history of this dynamic high-altitude contact zone, we sequenced the genomes (0.04×–7.25×, mean 2.16×) and mitochondrial genomes (20.8×–1,311.0×, mean 482.1×) of eight individuals dating to three periods with distinct material culture in the Annapurna Conservation Area (ACA) of Nepal, spanning 3,150–1,250 y before present (yBP). We demonstrate that the region is characterized by long-term stability of the population genetic make-up despite marked changes in material culture. The ancient genomes, uniparental haplotypes, and high-altitude adaptive alleles suggest a high-altitude East Asian origin for prehistoric Himalayan populations.

Interestingly, all reads from our ACA individuals match the derived allele for the nonsynonymous EGLN1 SNP rs186996510 (SI Appendix, Table S2), including the oldest Chokhopani sample (C1). This derived allele, c.12G > C (p.Asp4Glu), is reported in high frequency in Tibetans (0.64–0.85) (22, 37), but is rare in low-altitude East Asians (0.03 in 1KG phase 3 East Asians) and virtually absent outside East Asia. Functional studies have implicated this allele as playing a role in oxygen homeostasis under hypoxic conditions (37, 39). In contrast, reads supporting derived alleles at the EPAS1 SNPs were found in two of the three later Samdzong individuals (S35 and S41), but not in the earlier Chokhopani (C1) or Mebrak (M63) individuals.