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Genomic analysis identified a potential novel molecular mechanism for high-altitude adaptation in sheep at the Himalayas.

ABSTRACT: Sheep has successfully adapted to the extreme high-altitude Himalayan region. To identify genes underlying such adaptation, we genotyped genome-wide single nucleotide polymorphisms (SNPs) of four major sheep breeds living at different altitudes in Nepal and downloaded SNP array data from additional Asian and Middle East breeds. Using a di value-based genomic comparison between four high-altitude and eight lowland Asian breeds, we discovered the most differentiated variants at the locus of FGF-7 (Keratinocyte growth factor-7), which was previously reported as a good protective candidate for pulmonary injuries. We further found a SNP upstream of FGF-7 that appears to contribute to the divergence signature. First, the SNP occurred at an extremely conserved site. Second, the SNP showed an increasing allele frequency with the elevated altitude in Nepalese sheep. Third, the electrophoretic mobility shift assays (EMSA) analysis using human lung cancer cells revealed the allele-specific DNA-protein interactions. We thus hypothesized that FGF-7 gene potentially enhances lung function by regulating its expression level in high-altitude sheep through altering its binding of specific transcription factors. Especially, FGF-7 gene was not implicated in previous studies of other high-altitude species, suggesting a potential novel adaptive mechanism to high altitude in sheep at the Himalayas.

SUBMITTER: Gorkhali NA

PROVIDER: S-EPMC4995607 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Genomic analysis identified a potential novel molecular mechanism for high-altitude adaptation in sheep at the Himalayas.

Gorkhali Neena Amatya NA Dong Kunzhe K Yang Min M Song Shen S Kader Adiljian A Shrestha Bhola Shankar BS He Xiaohong X Zhao Qianjun Q Pu Yabin Y Li Xiangchen X Kijas James J Guan Weijun W Han Jianlin J Jiang Lin L Ma Yuehui Y

Scientific reports 20160722

Sheep has successfully adapted to the extreme high-altitude Himalayan region. To identify genes underlying such adaptation, we genotyped genome-wide single nucleotide polymorphisms (SNPs) of four major sheep breeds living at different altitudes in Nepal and downloaded SNP array data from additional Asian and Middle East breeds. Using a di value-based genomic comparison between four high-altitude and eight lowland Asian breeds, we discovered the most differentiated variants at the locus of FGF-7 ...[more]

PMID: 27444145

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Project description:High altitudes (>8,000 ft or 2,500 m) provide an experiment of nature for measuring adaptation and the physiological processes involved. Studies conducted over the past ~25 years in Andeans, Tibetans, and, less often, Ethiopians show varied but distinct O2 transport traits from those of acclimatized newcomers, providing indirect evidence for genetic adaptation to high altitude. Short-term (acclimatization, developmental) and long-term (genetic) responses to high altitude exhibit a temporal gradient such that, although all influence O2 content, the latter also improve O2 delivery and metabolism. Much has been learned concerning the underlying physiological processes, but additional studies are needed on the regulation of blood flow and O2 utilization. Direct evidence of genetic adaptation comes from single-nucleotide polymorphism (SNP)-based genome scans and whole genome sequencing studies that have identified gene regions acted upon by natural selection. Efforts have begun to understand the connections between the two with Andean studies on the genetic factors raising uterine blood flow, fetal growth, and susceptibility to Chronic Mountain Sickness and Tibetan studies on genes serving to lower hemoglobin and pulmonary arterial pressure. Critical for future studies will be the selection of phenotypes with demonstrable effects on reproductive success, the calculation of actual fitness costs, and greater inclusion of women among the subjects being studied. The well-characterized nature of the O2 transport system, the presence of multiple long-resident populations, and relevance for understanding hypoxic disorders in all persons underscore the importance of understanding how evolutionary adaptation to high altitude has occurred.NEW & NOTEWORTHY Variation in O2 transport characteristics among Andean, Tibetan, and, when available, Ethiopian high-altitude residents supports the existence of genetic adaptations that improve the distribution of blood flow to vital organs and the efficiency of O2 utilization. Genome scans and whole genome sequencing studies implicate a broad range of gene regions. Future studies are needed using phenotypes of clear relevance for reproductive success for determining the mechanisms by which naturally selected genes are acting.

Dataset Information

Genomic analysis identified a potential novel molecular mechanism for high-altitude adaptation in sheep at the Himalayas.

Publications

Genomic analysis identified a potential novel molecular mechanism for high-altitude adaptation in sheep at the Himalayas.

Similar Datasets

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