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

Tony Yu Chen Tsai, Sup Choi Yoon, Wenzhe Ma, Joseph R. Pomerening, Chao Tang, James E. Ferrell

Research output: Contribution to journalArticlepeer-review

510 Scopus citations

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.

Original languageEnglish
Pages (from-to)126-139
Number of pages14
JournalScience
Volume321
Issue number5885
DOIs
StatePublished - Jul 4 2008

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