错误翻译引起的蛋白质错误折叠是编码序列进化的主要约束因素.
D Allan Drummond1, Claus O Wilke
1FAS Center for Systems Biology, Harvard University, Cambridge, MA 02138, USA. dadrummond@cgr.harvard.edu
Cell
|July 30, 2008
概括
由核糖体错误引起的有毒错折蛋白的选择解释了跨物种的基因进化和表达模式. 这一发现影响了对分子进化和神经退行性疾病的理解.
科学领域:
- 进化生物学是进化的生物学.
- 分子生物学分子生物学
- 遗传学 遗传学是一种遗传学.
背景情况:
- 编码序列进化速率和跨种群的基因表达水平之间存在一致的相关性.
- 讨论了推动这些相关性的潜在选择性压力.
- 之前的研究指出了序列演变,密码子使用和mRNA水平的趋势,但统一的原因尚不清楚.
研究的目的:
- 为了在不同物种中展示序列演变,编码子使用和mRNA水平之间的协同变异的保存模式.
- 确定这些观察到的趋势背后的统一选择性压力.
- 提出和验证一个驱动这些进化模式的分子机制.
主要方法:
- 对细菌大肠杆菌,酵母,虫,,老鼠和人类的序列演变,代码使用和mRNA水平的比较分析.
- 分子级进化模拟,模拟核糖体错误和蛋白质错折的影响.
- 分析元动物组织,特别是神经元的趋势.
主要成果:
- 在所有研究的种群中观察到保留的协同变异模式,这表明存在统一的选择压力.
- 这些趋势在神经元组织中最为明显,与对蛋白质错折的敏感性有关.
- 模拟表明,由核糖体错误引起的错误折叠蛋白质对毒性的选择可以产生观察到的协同变异.
结论:
- 错误折叠蛋白质的毒性选择是序列演变,编码子使用和mRNA水平之间观察到的协同变异的主要驱动因素.
- 拟议的模型挑战了非同义词与同义词替换比率 (Ka/Ks) 检测功能选择的实用性.
- 错误翻译可能在神经退行性疾病的病因学中发挥重要作用.
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