title: Robust, tunable biological oscillations from interlinked positive and negative feedback loops.
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.
authors.affiliation: Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA 94305-5174, USA.
authors.forename: Tony Yu-Chen
authors.initials: TY
authors.lastname: Tsai
authors.forename: Yoon Sup
authors.initials: YS
authors.lastname: Choi
authors.forename: Wenzhe
authors.initials: W
authors.lastname: Ma
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Pomerening
authors.forename: Chao
authors.initials: C
authors.lastname: Tang
authors.forename: James E
authors.initials: JE
authors.lastname: Ferrell
mesh_terms: D000465:Algorithms; D064173:Anaphase-Promoting Complex-Cyclosome; D000818:Animals; D001683:Biological Clocks; D005075:Biological Evolution; D016203:CDC2 Protein Kinase / Q000378:metabolism*; D002453:Cell Cycle; D002455:Cell Division; D002940:Circadian Rhythm; D019926:Cyclin B / Q000096:biosynthesis / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000378:metabolism; D025461:Feedback, Physiological; D007399:Interphase; D008954:Models, Biological; D009010:Monte Carlo Method; D043743:Ubiquitin-Protein Ligase Complexes / Q000378:metabolism; D029867:Xenopus Proteins / Q000378:metabolism; D014982:Xenopus laevis
chemical_list: D019926:Cyclin B; D029867:Xenopus Proteins; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome; D016203:CDC2 Protein Kinase