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基因突变率高于基因组错误值的可扩展,持续的进化
Arjun Ravikumar1, Garri A Arzumanyan1, Muaeen K A Obadi1
1Department of Biomedical Engineering, University of California, Irvine, Irvine, CA 92697, USA.
Cell
|November 13, 2018
概括
定向进化得到了增强,这是一个酵母系统,可以实现快速,高吞吐量基因突变和进化. 这种可扩展的工具加速了生物分子功能和适应性的研究.
科学领域:
- 生物化学
- 分子生物学
- 合成生物学
背景情况:
- 定向进化对于工程生物分子和理解适应至关重要.
- 目前的方法是劳动密集型和低吞吐量,限制了复杂的功能研究.
- 用现有的技术复制分子进化研究具有挑战性.
研究的目的:
- 开发一个高吞吐量,可扩展的系统,
- 克服生物分子工程现有实验策略的局限性.
- 为了实现细胞功能的常规和快速演变.
主要方法:
- 在酵母中开发OrthoRep,一个正交的DNA聚合酶-等离子体对.
- 它们的突变率比宿主基因组高10万倍.
- 使用序列传递进行连续和快速的基因进化.
主要成果:
- 在90个独立的复制物中成功演化了耐药性疟疾二酸减少酶 (DHFR).
- 揭示了一个复杂的健身格局,
- 发现了罕见的适应性结果和影响进化的非最佳适应性峰值.
结论:
- 提供一个简单,可扩展和高吞吐量平台,
- 能够对复杂的进化动态和健身景观进行常规调查.
- 开辟了生物分子和细胞功能的新途径.
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