现代人类的阿里碳水化合物受体在通过基因组编辑进行祖先化时更活跃
Nelly Helmbrecht1, Martin Lackner1, Tomislav Maricic1
1Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Leipzig D-04103, Germany.
概括
由于古老的遗传变化,现代人类具有较不活跃的酸受体 (AHR). 这种类似尼安德特人的AHR变体显示了基因激活的减少,影响了芳香碳化合物代谢.
科学领域:
- 人类进化人类的进化.
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- 酸受体 (AHR) 是一个关键的转录因子,调节基因表达,特别是对于像P450细胞染色体这样的解毒酶.
- 在AHR的位置381的一个特定的氨基酸替代区分了现代人类与尼安德特人和丹尼索瓦人等古老的原始人.
研究的目的:
- 调查祖先 (尼安德特人类) 和现代人类AHR之间的功能差异.
- 确定381位置换对AHR的转录活性和连接体响应性的影响.
主要方法:
- 利用基因组编辑创建表达祖先AHR变异的人类细胞.
- 在具有祖先和现代AHR的细胞中对AHR点基因的基因表达的比较.
- 评估了针对两个AHR变体的特定配体对目标基因的剂量依赖诱导.
主要成果:
- 与现代AHR细胞相比,表达祖先AHR的细胞表现出AHR目标基因的较高基底表达.
- 祖先的AHR显示的活动水平与黑猩猩的AHR相当.
- 现代人类的AHR需要显著更高的配体度来诱导目标基因表达,而不是祖先的AHR.
结论:
- 现代人类在381位的氨基酸替代导致了基碳化合物受体的诱导能力的降低.
- 这种进化变化可能改变了现代人类群体中芳香碳化合物的代谢处理.
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