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Robust, Tunable Biological Oscillations from Interlinked Positive and Negative Feedback Loops
Tsai, T. Y.-C.,Choi, Y. S.,Ma, W.,Pomerening, J. R.,Tang, C.,Ferrell, J. E. American Association for the Advancement of Scienc 2008 Science Vol.321 No.5885
<P>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.</P>