Wide distribution and altitude correlation of an archaic high-altitude-adaptive EPAS1 haplotype in the Himalayas.pdf (1.94 MB)
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Wide distribution and altitude correlation of an archaic high-altitude-adaptive EPAS1 haplotype in the Himalayas.

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journal contribution
posted on 23.11.2016, 13:34 by S. Hackinger, T. Kraaijenbrink, Y. Xue, M. Mezzavilla, Asan, G. van Driem, Mark A. Jobling, P. de Knijff, C. Tyler-Smith, Q. Ayub
High-altitude adaptation in Tibetans is influenced by introgression of a 32.7-kb haplotype from the Denisovans, an extinct branch of archaic humans, lying within the endothelial PAS domain protein 1 (EPAS1), and has also been reported in Sherpa. We genotyped 19 variants in this genomic region in 1507 Eurasian individuals, including 1188 from Bhutan and Nepal residing at altitudes between 86 and 4550 m above sea level. Derived alleles for five SNPs characterizing the core Denisovan haplotype (AGGAA) were present at high frequency not only in Tibetans and Sherpa, but also among many populations from the Himalayas, showing a significant correlation with altitude (Spearman's correlation coefficient = 0.75, p value 3.9 × 10(-11)). Seven East- and South-Asian 1000 Genomes Project individuals shared the Denisovan haplotype extending beyond the 32-kb region, enabling us to refine the haplotype structure and identify a candidate regulatory variant (rs370299814) that might be interacting in an additive manner with the derived G allele of rs150877473, the variant previously associated with high-altitude adaptation in Tibetans. Denisovan-derived alleles were also observed at frequencies of 3-14% in the 1000 Genomes Project African samples. The closest African haplotype is, however, separated from the Asian high-altitude haplotype by 22 mutations whereas only three mutations, including rs150877473, separate the Asians from the Denisovan, consistent with distant shared ancestry for African and Asian haplotypes and Denisovan adaptive introgression.

Funding

SH, YX, MM, CTS and QA were supported by The Wellcome Trust (098051), and MAJ by a Wellcome Trust Senior Fellowship (087576).

History

Citation

Human Genetics, (2016) 135: 393.

Author affiliation

/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/MBSP Non-Medical Departments/Department of Genetics

Version

VoR (Version of Record)

Published in

Human Genetics

issn

0340-6717

eissn

1432-1203

Copyright date

2016

Available date

23/11/2016

Publisher version

http://link.springer.com/article/10.1007/s00439-016-1641-2

Notes

The online version of this article (doi:10.1007/s00439-016-1641-2) contains supplementary material, which is available to authorized users.

Language

en