The Chemical Fluctuation Theorem governing gene expression

Seong Jun Park, Sanggeun Song, Gil-Suk Yang, Philip M. Kim, Sangwoon Yoon (), Ji-Hyun Kim () and Jaeyoung Sung ()
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Seong Jun Park: Chung-Ang University
Sanggeun Song: Chung-Ang University
Gil-Suk Yang: Chung-Ang University
Philip M. Kim: University of Toronto
Sangwoon Yoon: Chung-Ang University
Ji-Hyun Kim: Chung-Ang University
Jaeyoung Sung: Chung-Ang University

Nature Communications, 2018, vol. 9, issue 1, 1-12

Abstract: Abstract Gene expression is a complex stochastic process composed of numerous enzymatic reactions with rates coupled to hidden cell-state variables. Despite advances in single-cell technologies, the lack of a theory accurately describing the gene expression process has restricted a robust, quantitative understanding of gene expression variability among cells. Here we present the Chemical Fluctuation Theorem (CFT), providing an accurate relationship between the environment-coupled chemical dynamics of gene expression and gene expression variability. Combined with a general, accurate model of environment-coupled transcription processes, the CFT provides a unified explanation of mRNA variability for various experimental systems. From this analysis, we construct a quantitative model of transcription dynamics enabling analytic predictions for the dependence of mRNA noise on the mRNA lifetime distribution, confirmed against stochastic simulation. This work suggests promising new directions for quantitative investigation into cellular control over biological functions by making complex dynamics of intracellular reactions accessible to rigorous mathematical deductions.

Date: 2018
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DOI: 10.1038/s41467-017-02737-0

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