Robust entrainment of circadian oscillators requires specific phase response curves

Biophys J. 2011 Jun 8;100(11):2557-65. doi: 10.1016/j.bpj.2011.04.043.


The circadian clocks keeping time in many living organisms rely on self-sustained biochemical oscillations entrained by external cues, such as light, to the 24-h cycle induced by Earth's rotation. However, environmental cues are unreliable due to the variability of habitats, weather conditions, or cue-sensing mechanisms among individuals. A tempting hypothesis is that circadian clocks have evolved so as to be robust to fluctuations in the signal that entrains them. To support this hypothesis, we analyze the synchronization behavior of weakly and periodically forced oscillators in terms of their phase response curve (PRC), which measures phase changes induced by a perturbation applied at different times of the cycle. We establish a general relationship between the robustness of key entrainment properties, such as stability and oscillator phase, on the one hand, and the shape of the PRC as characterized by a specific curvature or the existence of a dead zone, on the other hand. The criteria obtained are applied to computational models of circadian clocks and account for the disparate robustness properties of various forcing schemes. Finally, the analysis of PRCs measured experimentally in several organisms strongly suggests a case of convergent evolution toward an optimal strategy for maintaining a clock that is accurate and robust to environmental fluctuations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Circadian Clocks / physiology*
  • Models, Biological*
  • Photoperiod
  • Reproducibility of Results