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Science. 2008 Jul 4;321(5885):126-9. doi: 10.1126/science.1156951.

Robust, tunable biological oscillations from interlinked positive and negative feedback loops.

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  • 1Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA 94305-5174, USA.

Abstract

A simple negative feedback loop of interacting genes or proteins has the potential to generate sustained oscillations. However, many biological oscillators also have a positive feedback loop, raising the question of what advantages the extra loop imparts. Through computational studies, we show that it is generally difficult to adjust a negative feedback oscillator's frequency without compromising its amplitude, whereas with positive-plus-negative feedback, one can achieve a widely tunable frequency and near-constant amplitude. This tunability makes the latter design suitable for biological rhythms like heartbeats and cell cycles that need to provide a constant output over a range of frequencies. Positive-plus-negative oscillators also appear to be more robust and easier to evolve, rationalizing why they are found in contexts where an adjustable frequency is unimportant.

PMID:
18599789
[PubMed - indexed for MEDLINE]
PMCID:
PMC2728800
Free PMC Article
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