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Independent control of mean and noise by convolution of gene expression distributions
bioRxiv - Synthetic Biology Pub Date : 2021-10-01 , DOI: 10.1101/2021.01.21.427519
Karl P. Gerhardt , Satyajit D. Rao , Evan J. Olson , Oleg A. Igoshin , Jeffrey J. Tabor

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 a single promoter. 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.

中文翻译:

通过基因表达分布的卷积独立控制均值和噪声

基因表达噪音会降低细胞适应性或促进替代代谢、抗生素抗性和分化等过程。不幸的是,研究噪音影响的努力受到噪音和来自单个启动子的表达水平之间的比例关系的阻碍。在这里,我们使用理论来证明可以通过在同一细胞中从不同的诱导型启动子表达基因的两个拷贝来独立控制均值和噪声。我们设计了低噪音和高噪音诱导型启动子,以在大肠杆菌中验证这一结果,并开发一个预测实验分布的模型。最后,我们使用我们的方法揭示了启动子对阻遏物的反应对阻遏物噪声较高的敏感性较低,并使用概率论中的定律解释这一结果。我们的方法可用于研究噪声对合成生物学应用的不同生物途径或程序细胞异质性的影响。
更新日期:2021-10-06
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