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

机译:基因组分析确定了喜马拉雅山绵羊高海拔适应的潜在新分子机制

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摘要

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.
机译:绵羊已经成功地适应了极高海拔的喜马拉雅地区。为了鉴定这种适应的基础基因,我们对生活在尼泊尔不同海拔的四个主要绵羊品种的全基因组范围内的单核苷酸多态性(SNP)进行了基因分型,并从其他亚洲和中东品种中下载了SNP阵列数据。通过在四个高海拔和八个低地亚洲品种之间进行基于双值的基因组比较,我们在FGF-7(角质形成细胞生长因子7)的位点发现了差异最大的变体,该变体先前曾被报道为可很好的保护肺部损伤。我们还发现了FGF-7上游的SNP,似乎有助于发散特征。首先,SNP发生在一个极为保守的地点。其次,随着尼泊尔绵羊海拔的升高,SNP显示等位基因频率增加。第三,使用人类肺癌细胞的电泳迁移率变动分析(EMSA)分析揭示了等位基因特异性的DNA-蛋白质相互作用。因此,我们假设FGF-7基因通过改变其与特定转录因子的结合来调节其在高海拔绵羊中的表达水平,从而潜在地增强了肺功能。尤其是,FGF-7基因没有涉及其他高海拔物种的先前研究,表明喜马拉雅山绵羊对高原的潜在新适应机制。

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