Robust, tunable biological oscillations from interlinked positive and negative feedback loops.
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.
Tsai
Tony Yu-Chen
TY
Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA 94305-5174, USA.
Choi
Yoon Sup
YS
Ma
Wenzhe
W
Pomerening
Joseph R
JR
Tang
Chao
C
Ferrell
James E
JE
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
D019926:Cyclin B; D029867:Xenopus Proteins; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome; D016203:CDC2 Protein Kinase