Evidence of Polygenic Adaptation to High Altitude from Tibetan and Sherpa Genomes
| Autor: | Marco Sazzini, Mingma G Sherpa, Donata Luiselli, Sara De Fanti, Marco Di Marcello, Stefania Sarno, Davide Peluzzi, Phurba T Sherpa, Davide Pettener, Giorgio Marinelli, Guido Alberto Gnecchi-Ruscone, Paolo Abondio, Luca Natali |
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| Přispěvatelé: | Gnecchi-Ruscone, Guido A, Abondio, Paolo, De Fanti, Sara, Sarno, Stefania, Sherpa, Mingma G, Sherpa, Phurba T, Marinelli, Giorgio, Natali, Luca, Di Marcello, Marco, Peluzzi, Davide, Luiselli, Donata, Pettener, Davide, Sazzini, Marco |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Multifactorial Inheritance Himalayan human populations Gene regulatory network Adaptation Biological Biology Tibet Genome 03 medical and health sciences Nepal Genetics Humans Selection Genetic Gene Ecology Evolution Behavior and Systematics Genome Human Altitude Himalayan human population polygenic adaptive traits 15. Life on land Effects of high altitude on humans hypobaric hypoxia Phenotype 030104 developmental biology Evolutionary biology Multigene Family Hypobaric hypoxia Adaptive evolution Research Article |
| Zdroj: | Genome Biology and Evolution |
| ISSN: | 1759-6653 |
| Popis: | Although Tibetans and Sherpa present several physiological adjustments evolved to cope with selective pressures imposed by the high-altitude environment, especially hypobaric hypoxia, few selective sweeps at a limited number of hypoxia related genes were confirmed by multiple genomic studies. Nevertheless, variants at these loci were found to be associated only with downregulation of the erythropoietic cascade, which represents an indirect aspect of the considered adaptive phenotype. Accordingly, the genetic basis of Tibetan/Sherpa adaptive traits remains to be fully elucidated, in part due to limitations of selection scans implemented so far and mostly relying on the hard sweep model. In order to overcome this issue, we used whole-genome sequence data and several selection statistics as input for gene network analyses aimed at testing for the occurrence of polygenic adaptation in these high-altitude Himalayan populations. Being able to detect also subtle genomic signatures ascribable to weak positive selection at multiple genes of the same functional subnetwork, this approach allowed us to infer adaptive evolution at loci individually showing small effect sizes, but belonging to highly interconnected biological pathways overall involved in angiogenetic processes. Therefore, these findings pinpointed a series of selective events neglected so far, which likely contributed to the augmented tissue blood perfusion observed in Tibetans and Sherpa, thus uncovering the genetic determinants of a key biological mechanism that underlies their adaptation to high altitude. |
| Databáze: | OpenAIRE |
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