Genetic Affinity of Newa Population of Kathmandu Valley and Changpa Population of Ladhak

Abstract

Nepal harbors a variety of ancient and indigenous haplogroups that have been largely ignored in several recent studies. To evaluate the matrilineal gene pool of the Himalayan populations and their genetic adaptation to the high-altitude hypoxia environment, 695 (508 newly generated) samples belonging to three different populations of Nepal (Newar, Magar and Brahmin) and 3 different populations from India (North India, Changpa and general individuals of Ladhak) were analyzed. Investigation was performed based on the high resolution mtDNA sequencing followed by the most precise identification of East Asian, Southeast Asian, South Asian and West Eurasian Haplogroups. Further, Phylogeographic analysis of the genealogical lineages where obtained by comparing the whole mtDNA sequences of the studied populations with the other Asian populations. Desired variants of Epas1 and EDAR gene were obtained through direct sequencing. Newar are considered to be the original and ancient inhabitants of the Kathmandu valley but when and where the Newar people originated from remains contentious. Hypothesis are proposed to have shared ancestry with the East Eurasian, South Asian and West Eurasian. Present study revealed the presence of albeit limited, ancient and deep time depth South Asian lineages in Newar, Magar and Brahmin. Further, Newar experiences several waves of migration adding several East Asian, South Asian as well as West Eurasian lineages into Newar via multiple dispersal, from several distinct sources in different time, rather than just one or two major admixture events in the Neolithic/Bronze age. Most of the East Eurasian haplotype, observed in Newar, Magar and Brahmin branched off directly from the nodes occupied by the Tibetan lineage, albeit a few haplotypes were shared in between Nepali and Northeast Indian. Taking into account the previous studies on East Eurasian maternal components, now it is convincing that the major Genetic Influx from East Asia across the Himalayas into Nepal occurred in between 3-6 Kya and these lineages has made a hefty contribution to the modern gene pools of the Newar and Magar. Hence, our analysis supports a close genetic relationship between Newar and East Asian population with substantial genetic contribution from South Asia and West Eurasia. This was further supported by the analysis of the EPAS1 gene and 1540C variants of the EDAR gene. In a good agreement with the previous studies on Tibetans and Sherpa, high-altitude adaptation in Ladhak also identified positive signal of selection in genetic variants of EPAS1 gene. Further, a strong linear correlation between genotyped alleles of EPAS1 gene and different level of altitude were detected in the Himalayan populations, suggesting that extremely high-altitude hypoxia environment exert a selective effect on Epas1 variants. Changpa shares most of their matrilineal lineages with the indigenous Tibetans suggesting that the Tibetans are the ancestral populations of Changpa and the adaptive traits for the high-altitude adaptation has been recently inherited form their ancestors in Tibet. Whereas the general individuals from Ladhak shows higher proportion of West Eurasian maternal components with substantial genetic contribution from Tibet and India.