Abstract：
Both genomics- and proteomics-based investigations have identified several essential genes, proteins, and pathways that may facilitate human adaptive genotype/phenotype in a population-specific manner. This comprehensive review provides an up-to-date list of genes and proteins identified for human adaptive responses to high altitudes. Genomics studies for indigenous high-altitude populations like Tibetans, Andeans, Ethiopians, and Sherpas have identified 169 genes under positive natural selection. Similarly, global proteomics studies have identified 258 proteins (± 1.2-fold or more) for Tibetan, Sherpa, and Ladakhi highlanders. The primary biological processes identified for genetic signatures include hypoxia-inducible factor (HIF)-mediated oxygen sensing, angiogenesis, and erythropoiesis. In contrast, major biological processes identified for proteomics signatures include 14-3-3 mediated sirtuin signaling, integrin-linked kinase (ILK), phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT), and integrin signaling. Comparing genetic and protein signatures, we identified 7 common genes/proteins (HBB/hemoglobin subunit beta, TF/serotransferrin, ANGPTL4/angiopoietin-related protein 4, CDC42/cell division control protein 42 homolog, GC/vitamin D-binding protein, IGFBP1/insulin-like growth factor-binding protein 1, and IGFBP2/insulin-like growth factor-binding protein 2) involved in crucial molecular functions like IGF-1 signaling, LXR/RXR activation, ferroptosis signaling, iron homeostasis signaling and regulation of cell cycle. Our combined multi-omics analysis identifies common molecular targets and pathways for human adaptation to high altitude. These observations further corroborate convergent positive selection of hypoxia-responsive molecular pathways in humans and advocate using multi-omics techniques for deciphering human adaptive responses to high altitude.
摘要：
基于基因组学和蛋白质组学的研究已经确定了几个必需的基因，蛋白质，和可能以群体特异性方式促进人类适应性基因型/表型的途径。这份全面的综述提供了为人类对高海拔地区的适应性反应而确定的最新基因和蛋白质列表。针对藏人等土著高海拔人口的基因组学研究，Andeans,埃塞俄比亚人,和夏尔巴人已经确定了169个基因在积极的自然选择。同样，全球蛋白质组学研究已经确定了藏人的258种蛋白质（±1.2倍或更多），夏尔巴,还有拉达基高地人.确定遗传特征的主要生物过程包括缺氧诱导因子（HIF）介导的氧感应，血管生成,和红细胞生成。相比之下,确定蛋白质组学特征的主要生物学过程包括14-3-3介导的沉默调节蛋白信号，整合素连接激酶（ILK），磷酸肌醇3-激酶（PI3K）/蛋白激酶B（AKT），和整合素信号。比较遗传和蛋白质特征，我们确定了7种常见的基因/蛋白质（HBB/血红蛋白亚基β，TF/血清转铁蛋白，ANGPTL4/血管生成素相关蛋白4，CDC42/细胞分裂控制蛋白42同源物，GC/维生素D结合蛋白，IGFBP1/胰岛素样生长因子结合蛋白1和IGFBP2/胰岛素样生长因子结合蛋白2）参与IGF-1信号传导等关键分子功能，LXR/RXR激活，铁凋亡信号，铁稳态信号和细胞周期的调节。我们的联合多组学分析确定了人类适应高海拔的常见分子靶标和途径。这些观察结果进一步证实了人类对缺氧反应分子途径的趋同正选择，并提倡使用多组学技术来破译人类对高海拔地区的适应性反应。
