Mechanisms of noise-resistance in genetic oscillators
- *Howard Hughes Medical Institute, Departments of Molecular Biology and Physics, Princeton University, Princeton, NJ 08544; †The Rockefeller University, 1230 York Avenue, New York, NY 10021; and ‡Departments of Molecular Genetics and Physics of Complex Systems, Weizmann Institute of Science, Rehovot 76100, Israel
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Communicated by Michael E. Fisher, University of Maryland, College Park, MD (received for review November 6, 2001)
Abstract
A wide range of organisms use circadian clocks to keep internal sense of daily time and regulate their behavior accordingly. Most of these clocks use intracellular genetic networks based on positive and negative regulatory elements. The integration of these “circuits” at the cellular level imposes strong constraints on their functioning and design. Here, we study a recently proposed model [Barkai, N. & Leibler, S. (2000) Nature (London), 403, 267–268] that incorporates just the essential elements found experimentally. We show that this type of oscillator is driven mainly by two elements: the concentration of a repressor protein and the dynamics of an activator protein forming an inactive complex with the repressor. Thus, the clock does not need to rely on mRNA dynamics to oscillate, which makes it especially resistant to fluctuations. Oscillations can be present even when the time average of the number of mRNA molecules goes below one. Under some conditions, this oscillator is not only resistant to but, paradoxically, also enhanced by the intrinsic biochemical noise.
Footnotes
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↵ § To whom reprint requests should be addressed at: The Rockefeller University, Box 34, 1230 York Avenue, New York, NY 10021.
- Copyright © 2002, The National Academy of Sciences
