人类遗传适应与细胞平衡相关
Ana Roca-Umbert1, Jorge Garcia-Calleja1, Marina Vogel-González2
1Institut de Biologia Evolutiva (UPF-CSIC), Departament de Medicina i Ciències de la Vida, Universitat Pompeu Fabra, Parc de Recerca Biomèdica de Barcelona, Barcelona, Spain.
PLoS genetics
|September 25, 2023
概括
人类进化涉及选择一种载体 (ZnT9) 变体,可能是由寒冷适应驱动的. 这种遗传变化会影响细胞功能,并可能影响神经精神疾病的易感性.
科学领域:
- 人类进化遗传学人类进化遗传学
- 分子生物学分子生物学
- 人类适应的人类适应
背景情况:
- 编码载体9 (ZnT9) 的SLC30A9是人类进化中积极选择的候选者.
- 以前的研究表明适应性选择,但缺乏直接的分子表型.
研究的目的:
- 为了研究SLC30A9.9的适应性分子表型.
- 探索特定单元型和Met50Val替代 (rs1047626) 在人类适应中的作用.
- 了解ZnT9变体对细胞处理和新陈代谢的功能影响.
主要方法:
- 人类类型和选择特征的分析.
- 对于rs1047626多态的基因定型.
- 在HEK293细胞中进行功能测试,以比较ZnT9 50Met和50Val异型.
- 评估线粒体和内质网膜中的处理.
- 对线粒体代谢的影响评估.
主要成果:
- 在与差异性基因表达相关的非洲和东亚单体类型中发现的定向选择.
- 在丹尼索瓦人中存在的ZnT9中的Met50Val替代 (rs1047626) 显示了古老的内进的签名.
- 与祖先的50Met形式相比,衍生的ZnT9 50Val异型在细胞测试中表现出功能的增加.
- ZnT9 50Val变体改变了线粒体和内质网膜中的处理,影响了线粒体代谢.
结论:
- 在ZnT9中Met50Val的替代代表了功能性适应性变化,可能是由适应寒冷环境所驱动的.
- 这种进化适应可能对线粒体功能和现代人类神经精神疾病的倾向产生影响.
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