Laboratoire de Physique des Lasers, Atomes, Molécules, and Institut de Recherche Interdisciplinaire, Université Lille 1 Sciences et Technologies, CNRS, F-59655 Villeneuve d'Ascq, France.
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.
许多生物的生物钟依赖于自我维持的生化振荡，这些振荡受外部线索（如光）的影响，与地球自转引起的 24 小时周期同步。然而，由于栖息地的可变性、天气条件或个体之间的线索感应机制，环境线索并不可靠。一个诱人的假设是，生物钟已经进化到能够抵抗它们所依赖的信号波动。为了支持这一假设，我们根据相位反应曲线（PRC）分析了弱周期性强迫振荡器的同步行为，该曲线测量了在周期不同时间施加的扰动引起的相位变化。我们建立了一个一般关系，一方面是关键的同步特性（如稳定性和振荡器相位）的稳健性，另一方面是 PRC 的形状，其特征是特定的曲率或存在死区。所获得的标准应用于生物钟的计算模型，并解释了各种强迫方案的不同稳健性特性。最后，对几种生物体内测量的 PRC 的分析强烈表明，存在一种趋同进化的情况，即朝着一种能够精确和稳健地应对环境波动的时钟的最佳策略发展。
