Abstract

Cells are intrinsically noisy biochemical reactors: low reactant numbers can lead to significant statistical fluctuations in molecule numbers and reaction rates. Here we use an analytic model to investigate the emergent noise properties of genetic systems. We find for a single gene that noise is essentially determined at the translational level, and that the mean and variance of protein concentration can be independently controlled. The noise strength immediately following single gene induction is almost twice the final steady-state value. We find that fluctuations in the concentrations of a regulatory protein can propagate through a genetic cascade; translational noise control could explain the inefficient translation rates observed for genes encoding such regulatory proteins. For an autoregulatory protein, we demonstrate that negative feedback efficiently decreases system noise. The model can be used to predict the noise characteristics of networks of arbitrary connectivity. The general procedure is further illustrated for an autocatalytic protein and a bistable genetic switch. The analysis of intrinsic noise reveals biological roles of gene network structures and can lead to a deeper understanding of their evolutionary origin.

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Acknowledgments

We thank H. S. Seung for asking the first questions that prompted us to study genetic networks, D. G. Greenhouse and T. A. Bass for useful discussions, and J. Werfel and R. Metzler for critically reviewing the manuscript.

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Information & Authors

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Published in

Go to Proceedings of the National Academy of Sciences
Proceedings of the National Academy of Sciences
Vol. 98 | No. 15
July 17, 2001
PubMed: 11438714

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Submission history

Received: December 12, 2000
Published online: July 3, 2001
Published in issue: July 17, 2001

Acknowledgments

We thank H. S. Seung for asking the first questions that prompted us to study genetic networks, D. G. Greenhouse and T. A. Bass for useful discussions, and J. Werfel and R. Metzler for critically reviewing the manuscript.

Authors

Affiliations

Mukund Thattai
Department of Physics, Room 13-2010, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139
Alexander van Oudenaarden*
Department of Physics, Room 13-2010, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139

Notes

*
To whom reprint requests should be addressed. E-mail: [email protected].
Edited by Peter G. Wolynes, University of California at San Diego, La Jolla, CA, and approved May 18, 2001

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    Intrinsic noise in gene regulatory networks
    Proceedings of the National Academy of Sciences
    • Vol. 98
    • No. 15
    • pp. 8159-8921

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