高海拔安第斯H194RHIF2A等位基因是一种低态等位基因基因
Kelsey Jorgensen1, Daisheng Song2, Julien Weinstein3
1Department of Anthropology, University of California, Los Angeles, CA, USA.
Molecular biology and evolution
|July 18, 2023
概括
高海拔的安第斯人携带一种特定的HIF2A基因变异 (H194R),可以提供对低氧的保护. 这种与氧化生产相关的低形态基因基降低了小鼠模型中肺高血压的风险.
科学领域:
- 人类遗传学 人类遗传学
- 生理适应生理适应
- 分子生物学分子生物学
背景情况:
- 安第斯人长期居住在高海拔地区,面临低氧水平带来的挑战.
- 以前的研究表明,在安第斯人中,HIF2A (低氧诱导因子2α) 基因的阳性选择.
- 选择的HIF2A等位基因对高度适应的功能影响仍然不清楚.
研究的目的:
- 调查秘鲁安第斯地区HIF2A位点的遗传变异和功能后果.
- 确定一个特定的安第斯HIF2A变异可能赋予高度适应的机制.
主要方法:
- 46名秘鲁安第斯人个体的全基因组测序.
- 在299个个体中对安第斯特异单核酸变体 (SNV) rs570553380 (H194R) 的基因定型.
- 实验室试验评估蛋白质与蛋白质相互作用,并使用 knockin 鼠标模型评估生理效应.
主要成果:
- 在安第斯人中确认了HIF2A的阳性选择,与H194R替代有关 (rs570553380).
- 这种H194R变体与增加的排气氧化分数正相关.
- 实验室研究显示,HIF-2α与其伴侣的结合受损;小鼠模型表现出低氧诱导的肺Endothelin-1减少以及对肺高血压的保护.
结论:
- 安第斯H194RHIF2A等位基因作为一个低形态 (部分功能丧失) 变体起作用.
- 这种等位基与改变的氧化代谢和对缺氧诱导的肺高血压的保护有关.
- 提供HIF2A介导适应高海拔环境的分子机制.
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