在现代人类进化过程中,腺酸酶的活性和表达减少,影响大脑和行为
Xiang-Chun Ju1, Shin-Yu Lee1, Richard Ågren2
1Okinawa Institute of Science and Technology Graduate University, Okinawa 904-0495, Japan.
概括
现代人类在腺酸酶 (ADSL) 中的遗传变化减少了酶活性,增加了纯素生物合成基质,特别是在大脑中. 这影响了小鼠的行为,雌性对水的获取有所改善.
科学领域:
- 生物化学 生物化学
- 进化生物学 进化生物学
- 神经科学是一个神经科学.
背景情况:
- 腺酸酶 (ADSL) 对于蛋白生物合成至关重要.
- 在ADSL中常见的人类氨基酸替代,在尼安德特人中不存在,降低了酶的稳定性.
- 这种替代对纯素代谢和人类进化的功能影响尚不清楚.
研究的目的:
- 调查现代人类ADSL替代的功能后果.
- 探索ADSL活动减少对氨酸生物合成和行为的影响.
- 检查人类ADSL遗传变化的进化影响.
主要方法:
- 在小鼠中引入了现代人类ADSL替代.
- 测量了ADSL基板积累和ADSL表达水平.
- 分析了小鼠的行为,重点关注水分和饮用效率.
- 研究了一种与ADSL表达减少和脑脊液基质水平增加相关的选定单元型.
主要成果:
- ADSL替代导致基质积累,与酶表达相反相关,特别是在大脑中.
- 具有类似人类ADSL的雌性小鼠表现出改善饮用水的机会.
- 在积极选择下,一个常见的人类ADSL单元型与ADSL表达率较低和脑脊液中氨酸氨酸水平较高有关.
结论:
- 自从从古人类分离出来以来,有两种遗传变化降低了人类的ADSL活动.
- 这些变化影响了纯氨酸生物合成,在大脑中产生了明显的影响.
- 这些发现提供了关于人类特定基因适应在代谢途径中的功能和进化影响的见解.
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