Independent control of mean and noise by convolution of gene expression distributions.
Independent control of mean and noise by convolution of gene expression distributions.
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DOI：
10.1038/s41467-021-27070-5
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发表时间：
2021-11-29
影响因子：
16.6
通讯作者：
Tabor JJ
中科院分区：
文献类型：
--
作者：
Gerhardt KP;Rao SD;Olson EJ;Igoshin OA;Tabor JJ
基因表达噪音可以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了噪音和单个启动子表达水平之间的比例关系的阻碍。在这里，我们用理论来证明，平均值和噪音可以通过在同一个细胞中从不同的诱导型启动子表达两个基因拷贝来独立控制。我们设计了低噪声和高噪声诱导型启动子，以验证这一结果在大肠杆菌中，并开发了一个模型，预测实验分布。最后，我们用我们的方法揭示了启动子对阻遏物的响应在阻遏物噪声较高的情况下不太敏感，并用概率论的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，或用于合成生物学应用的细胞异质性程序。基因表达噪声可以降低适应度，但噪声和表达水平之间的比例关系阻碍了分析。在这里，作者表明，基因表达的平均值和噪音可以通过在同一细胞中从不同的诱导型启动子表达两个基因拷贝来独立控制。
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. Gene expression noise can reduce fitness but analysis is hampered by a scaling relationship between noise and expression level. Here the authors show that gene expression mean and noise can be independently controlled by expressing two copies of a gene from separate inducible promoters in the same cell.