基因适应和尼安德特人的混合塑造了人类的免疫系统
Hélène Quach1, Maxime Rotival1, Julien Pothlichet1
1Human Evolutionary Genetics Unit, Institut Pasteur, Paris 75015, France; CNRS, URA3012, Paris 75015, France; Center of Bioinformatics, Biostatistics and Integrative Biology, Institut Pasteur, Paris 75015, France.
Cell
|October 22, 2016
概括
人类免疫反应因遗传因素而在不同人群之间有很大差异. 这项研究揭示了包括尼安德特人混合物在内的遗传变异如何影响这些差异,特别是在对病毒威胁的反应中.
科学领域:
- 免疫学
- 人类遗传学
- 进化生物学
背景情况:
- 人类在接触病原体后表现出不同的结果.
- 导致这些免疫反应差异的遗传和进化因素尚未完全理解.
研究的目的:
- 描述非洲和欧洲单细胞中的转录性免疫反应.
- 确定群体特异性免疫变异的遗传决定因素 (eQTL).
- 研究自然选择和古老混合物在塑造免疫反应中的作用.
主要方法:
- 非洲人和欧洲人的原始单细胞的RNA测序.
- 使用细菌和病毒配体激活托尔类受体 (TLR) 途径进行刺激.
- 表达量的特征位置 (eQTL) 的映射.
主要成果:
- 确定了许多解释免疫反应的群体差异的cis- eQTL.
- 在TLR1发现了一个跨eQTL热点,降低了欧洲人的炎症基因表达.
- 在自然选择的信号中发现了免疫反应变异的丰富.
- 已证明尼安德特人的添加物引入了影响欧洲人病毒反应的调节变异.
结论:
- 基因变异,包括 cis- 和 trans- eQTL,显著推动免疫反应的群体差异.
- 自然选择和古老的进攻塑造了人类免疫系统的进化.
- 了解这些决定因素对于解释宿主对病原体的不同反应至关重要.
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