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.

Keywords: Ancient DNA; EGLN1; EPAS1; high altitude; population genetics.

Fig. 1.

Map of the ACA and sampling locations. The ACA (dark gray), located in the Upper Mustang of north-central Nepal and bordering Tibet (Inset), is situated between the Annapurna and Dhaulagiri Massifs of the main Himalayan mountain range. The ACA includes 14 mountains in excess of 6,000 masl, and it contains a single major drainage, the Kali Gandaki River, which originates on the Tibetan plateau. Data from ref. .

Fig. 2.

PCA of East Asian populations and ancient ACA individuals. All five ACA samples cluster with Tibetans. PC1 and PC2 were calculated using all contemporary East Asian samples. Ancient ACA samples were projected onto the PC plane, using the “lsqproject: YES” option.

Fig. 3.

Unsupervised genetic clustering with two to nine ancestral populations (K = 2–9). All five ACA samples exhibit ancestry profiles most similar to Tibetans. The Sherpa, Tibetans, and ACA samples share a distinct high-altitude ancestry (red) in the highest proportions, followed by other Tibeto-Burman–speaking groups such as Naxi and Yi. K = 2 is shown at the bottom of the plot; K = 9 is shown at the top.

Fig. 4.

Genetic affinity of ACA individuals and East Asian populations, using genome-wide SNP data. (A) Genetic affinity with ancient sample C1 is measured by f₃ (Yoruba; ACA, X). For all ACA samples (SI Appendix, Fig. S9), either Sherpa or Tibetans were the closest modern population (a larger f₃ value indicates a closer relationship), followed by other Tibeto-Burman–speaking groups, such as Naxi and Yi. (B) All ACA samples are significantly more closely related to contemporary high-altitude East Asians than they are to lowland Tibeto-Burman–speaking groups, as shown by positive values of Patterson’s D (Yoruba, ACA; Yi, Tibetan.Lhasa). Equivalent results are observed if the test is performed with alternative proxy populations for high-altitude East Asians (e.g., Tibetan.Nepali or Sherpa) and lowland Tibeto-Burman speakers (e.g., Naxi or Tujia) (SI Appendix, Fig. S10).