Independent control of mean and noise by convolution of gene expression distributions
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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.
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Gerhardt, Karl P., Rao, Satyajit D., Olson, Evan J., et al.. "Independent control of mean and noise by convolution of gene expression distributions." Nature Communications, 12, (2021) Springer Nature: https://doi.org/10.1038/s41467-021-27070-5.