The history and evolution of the Denisovan-EPAS1 haplotype in Tibetans
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The history and evolution of the Denisovan-EPAS1 haplotype in Tibetans. / Zhang, Xinjun; Witt, Kelsey E.; Banuelos, Mayra M.; Ko, Amy; Yuan, Kai; Xu, Shuhua; Nielsen, Rasmus; Huerta-Sanchez, Emilia.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 118, No. 22, 2020803118, 2021.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - The history and evolution of the Denisovan-EPAS1 haplotype in Tibetans
AU - Zhang, Xinjun
AU - Witt, Kelsey E.
AU - Banuelos, Mayra M.
AU - Ko, Amy
AU - Yuan, Kai
AU - Xu, Shuhua
AU - Nielsen, Rasmus
AU - Huerta-Sanchez, Emilia
PY - 2021
Y1 - 2021
N2 - Recent studies suggest that admixture with archaic hominins played an important role in facilitating biological adaptations to new environments. For example, interbreeding with Denisovans facilitated the adaptation to high-altitude environments on the Tibetan Plateau. Specifically, the EPAS1 gene, a transcription factor that regulates the response to hypoxia, exhibits strong signatures of both positive selection and introgression from Denisovans in Tibetan individuals. Interestingly, despite being geographically closer to the Denisova Cave, East Asian populations do not harbor as much Denisovan ancestry as populations from Melanesia. Recently, two studies have suggested two independent waves of Denisovan admixture into East Asians, one of which is shared with South Asians and Oceanians. Here, we leverage data from EPAS1 in 78 Tibetan individuals to interrogate which of these two introgression events introduced the EPAS1 beneficial sequence into the ancestral population of Tibetans, and we use the distribution of introgressed segment lengths at this locus to infer the timing of the introgression and selection event. We find that the introgression event unique to East Asians most likely introduced the beneficial haplotype into the ancestral population of Tibetans around 48,700 (16,000-59,500) y ago, and selection started around 9,000 (2,500-42,000) y ago. Our estimates suggest that one of the most convincing examples of adaptive introgression is in fact selection acting on standing archaic variation.
AB - Recent studies suggest that admixture with archaic hominins played an important role in facilitating biological adaptations to new environments. For example, interbreeding with Denisovans facilitated the adaptation to high-altitude environments on the Tibetan Plateau. Specifically, the EPAS1 gene, a transcription factor that regulates the response to hypoxia, exhibits strong signatures of both positive selection and introgression from Denisovans in Tibetan individuals. Interestingly, despite being geographically closer to the Denisova Cave, East Asian populations do not harbor as much Denisovan ancestry as populations from Melanesia. Recently, two studies have suggested two independent waves of Denisovan admixture into East Asians, one of which is shared with South Asians and Oceanians. Here, we leverage data from EPAS1 in 78 Tibetan individuals to interrogate which of these two introgression events introduced the EPAS1 beneficial sequence into the ancestral population of Tibetans, and we use the distribution of introgressed segment lengths at this locus to infer the timing of the introgression and selection event. We find that the introgression event unique to East Asians most likely introduced the beneficial haplotype into the ancestral population of Tibetans around 48,700 (16,000-59,500) y ago, and selection started around 9,000 (2,500-42,000) y ago. Our estimates suggest that one of the most convincing examples of adaptive introgression is in fact selection acting on standing archaic variation.
KW - adaptation
KW - archaic introgression
KW - high altitude
KW - natural selection
KW - admixture
KW - PERMANENT HUMAN OCCUPATION
KW - ADAPTIVE INTROGRESSION
KW - BAYESIAN COMPUTATION
KW - ALTITUDE ADAPTATION
KW - POPULATION HISTORY
KW - GENETIC-EVIDENCE
KW - GENOME SEQUENCE
KW - NEANDERTHAL
KW - ADMIXTURE
KW - CAVE
U2 - 10.1073/pnas.2020803118
DO - 10.1073/pnas.2020803118
M3 - Journal article
C2 - 34050022
VL - 118
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 22
M1 - 2020803118
ER -
ID: 272429468