Department of Bioengineering, Rice University, 6100 Main Street, Houston, TX, 77005, USA.
Department of Biosciences, Rice University, 6100 Main Street, Houston, TX, 77005, USA.
Nat Commun. 2021 Nov 29;12(1):6957. doi: 10.1038/s41467-021-27070-5.
Gene expression noise can reduce cellular fitness or facilitate processes such as alternative metabolism, antibiotic resistance, and differentiation. Unfortunately, efforts to study the impacts of noise have been hampered by a scaling relationship between noise and expression level from individual promoters. Here, we use theory to demonstrate that mean and noise can be controlled independently by expressing two copies of a gene from separate inducible promoters in the same cell. We engineer low and high noise inducible promoters to validate this result in Escherichia coli, and develop a model that predicts the experimental distributions. Finally, we use our method to reveal that the response of a promoter to a repressor is less sensitive with higher repressor noise and explain this result using a law from probability theory. Our approach can be applied to investigate the effects of noise on diverse biological pathways or program cellular heterogeneity for synthetic biology applications.
基因表达噪声会降低细胞适应性，或促进替代代谢、抗生素耐药性和分化等过程。遗憾的是，由于单个启动子的噪声与表达水平之间存在一种比例关系，因此研究噪声影响的工作受到了阻碍。在这里，我们利用理论证明，通过在同一个细胞中使用两个独立诱导启动子表达同一个基因，可以独立控制平均值和噪声。我们设计了低噪声和高声噪诱导启动子，在大肠杆菌中验证了这一结果，并开发了一个可以预测实验分布的模型。最后，我们使用这种方法揭示了在更高的抑制子噪声下，启动子对抑制子的反应不那么敏感，并使用概率论中的一个定律解释了这一结果。我们的方法可以应用于研究噪声对不同生物途径的影响，或者为合成生物学应用程序设计细胞异质性。
