深度突变扫描揭示了RNA聚合酶介导适应和权衡的分子决定因素
Alaksh Choudhury1,2, Benoit Gachet3, Zoya Dixit3,4
1Université de Paris Cité, INSERM, IAME, UMR 1137, 75018, Paris, France. alaksh.choudhury@espci.fr.
Nature communications
|October 9, 2023
概括
像RpoB这样的RNA聚合酶 (RNAP) 子单元中的突变可以适应以实现更快的生长或更好的维护. 结合这些适应同时改善了两者,挑战了现有的权衡理论.
科学领域:
- 分子生物学分子生物学
- 进化生物学 进化生物学
- 系统生物学 系统生物学
背景情况:
- RNA聚合酶 (RNAP) 调节重要的生物权衡,例如生长与维持.
- 在实验室进化研究中经常观察到RNAP子单元,特别是RpoB的突变.
- 缺乏系统层面的理解RNAP突变如何驱动适应.
研究的目的:
- 在rpoB基因的特定区域内研究众多突变的功能后果.
- 了解这些突变如何在不同的条件下影响RNAP分子功能和细胞健康.
- 阐明RNAP介导的适应和权衡背后的机制.
主要方法:
- 系统测量适合数千个rpoB突变在各种条件和遗传背景的系统测量.
- 分析突变聚类,以确定RNAP中的功能模块.
- 分子机制的表征,包括RNAP-DNA复合体的稳定性和延长率.
主要成果:
- 发现rpoB中的适应性突变聚集在两个不同的模块中.
- 一个模块的突变通过增加延长速度来增强增长而不是维护.
- 另一模块的突变通过破坏RNAP-DNA复合物的稳定,有利于维持而不是增长.
结论:
- 在RNAP中,有两个关键的分子机制允许多功能适应,平衡生长和维护.
- 两个模块同时失去互动,改善了增长和维护.
- 这表明,维持增长的权衡不仅仅是资源有限的,而且可以通过补偿进化在RNAP中进行调节.
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