Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
University of Chinese Academy of Sciences, Beijing 100049, China.
Zool Res. 2024 Sep 18;45(5):1013-1026. doi: 10.24272/j.issn.2095-8137.2024.050.
DNA methylation plays a crucial role in environmental adaptations. Here, using whole-genome bisulfite sequencing, we generated comprehensive genome-wide DNA methylation profiles for the high-altitude Yunnan snub-nosed monkey ( ) and the closely related golden snub-nosed monkey ( ). Our findings indicated a slight increase in overall DNA methylation levels in golden snub-nosed monkeys compared to Yunnan snub-nosed monkeys, suggesting a higher prevalence of hypermethylated genomic regions in the former. Comparative genomic methylation analysis demonstrated that genes associated with differentially methylated regions were involved in membrane fusion, vesicular formation and trafficking, hemoglobin function, cell cycle regulation, and neuronal differentiation. These results suggest that the high-altitude-related epigenetic modifications are extensive, involving a complete adaptation process from the inhibition of single Ca channel proteins to multiple proteins collaboratively enhancing vesicular function or inhibiting cell differentiation and proliferation. Functional assays demonstrated that overexpression or down-regulation of candidate genes, such as , , and , influenced cell viability under stress conditions. Overall, this research suggests that comparing DNA methylation across closely related species can identify novel candidate genomic regions and genes associated with local adaptations, thereby deepening our understanding of the mechanisms underlying environmental adaptations.
DNA 甲基化在环境适应中起着至关重要的作用。在这里，我们使用全基因组亚硫酸氢盐测序，为高海拔的滇金丝猴（ ）和密切相关的仰鼻猴（ ）生成了全面的全基因组 DNA 甲基化图谱。我们的研究结果表明，与滇金丝猴相比，金丝猴的总体 DNA 甲基化水平略有升高，这表明前者的高甲基化基因组区域更为普遍。比较基因组甲基化分析表明，与差异甲基化区域相关的基因参与了膜融合、囊泡形成和运输、血红蛋白功能、细胞周期调控和神经元分化。这些结果表明，与高海拔相关的表观遗传修饰是广泛的，涉及从单个钙通道蛋白抑制到多个蛋白协同增强囊泡功能或抑制细胞分化和增殖的完整适应过程。功能分析表明，候选基因如 、 、 和 的过表达或下调会影响应激条件下的细胞活力。总的来说，这项研究表明，比较密切相关物种的 DNA 甲基化可以识别与局部适应相关的新候选基因组区域和基因，从而加深我们对环境适应机制的理解。
