Steady-state fluctuations of a genetic feedback loop: an exact solution

R. Grima, D. R. Schmidt, T. J. Newman

    Research output: Contribution to journalArticle

    34 Citations (Scopus)
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    Abstract

    Genetic feedback loops in cells break detailed balance and involve bimolecular reactions; hence, exact solutions revealing the nature of the stochastic fluctuations in these loops are lacking. We here consider the master equation for a gene regulatory feedback loop: a gene produces protein which then binds to the promoter of the same gene and regulates its expression. The protein degrades in its free and bound forms. This network breaks detailed balance and involves a single bimolecular reaction step. We provide an exact solution of the steady-state master equation for arbitrary values of the parameters, and present simplified solutions for a number of special cases. The full parametric dependence of the analytical non-equilibrium steady-state probability distribution is verified by direct numerical solution of the master equations. For the case where the degradation rate of bound and free protein is the same, our solution is at variance with a previous claim of an exact solution [J. E. M. Hornos, D. Schultz, G. C. P. Innocentini, J. Wang, A. M. Walczak, J. N. Onuchic, and P. G. Wolynes, Phys. Rev. E 72, 051907 (2005)10.1103/PhysRevE. 72.051907, and subsequent studies]. We show explicitly that this is due to an unphysical formulation of the underlying master equation in those studies.

    Copyright (2012) American Institute of Physics. This article may be downloaded for personal use only. Any other use requires prior permission of the author and the American Institute of Physics.

    The following article appeared in Journal of Chemical Physics, Vol. 137, No. 3, 2012, 035104, and may be found at http://link.aip.org/link/doi/10.1063/1.4736721
    Original languageEnglish
    Article number035104
    JournalJournal of Chemical Physics
    Volume137
    Issue number3
    DOIs
    Publication statusPublished - 2012

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