• Open Access

Cooperativity of Negative Autoregulation Confers Increased Mutational Robustness

David C. Marciano, Rhonald C. Lua, Christophe Herman, and Olivier Lichtarge
Phys. Rev. Lett. 116, 258104 – Published 22 June 2016
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Abstract

Negative autoregulation is universally found across organisms. In the bacterium Escherichia coli, transcription factors often repress their own expression to form a negative feedback network motif that enables robustness to changes in biochemical parameters. Here we present a simple phenomenological model of a negative feedback transcription factor repressing both itself and another target gene. The strength of the negative feedback is characterized by three parameters: the cooperativity in self-repression, the maximal expression rate of the transcription factor, and the apparent dissociation constant of the transcription factor binding to its own promoter. Analysis of the model shows that the target gene levels are robust to mutations in the transcription factor, and that the robustness improves as the degree of cooperativity in self-repression increases. The prediction is tested in the LexA transcriptional network of E. coli by altering cooperativity in self-repression and promoter strength. Indeed, we find robustness is correlated with the former. Considering the proposed importance of gene regulation in speciation, parameters governing a transcription factor’s robustness to mutation may have significant influence on a cell or organism’s capacity to evolve.

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  • Received 24 June 2015

DOI:https://doi.org/10.1103/PhysRevLett.116.258104

This article is available under the terms of the Creative Commons Attribution 3.0 License. Further distribution of this work must maintain attribution to the author(s) and the published article’s title, journal citation, and DOI.

Published by the American Physical Society

Physics Subject Headings (PhySH)

Physics of Living Systems

Authors & Affiliations

David C. Marciano1, Rhonald C. Lua1, Christophe Herman1, and Olivier Lichtarge1,2,3,*

  • 1Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA
  • 2Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas 77030, USA
  • 3Computational and Integrative Biomedical Research Center, Baylor College of Medicine, Houston, Texas 77030, USA

  • *Corresponding author. lichtarge@bcm.edu

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Vol. 116, Iss. 25 — 24 June 2016

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