Circadian rhythms and molecular noise
Circadian rhythms and molecular noise
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DOI：
10.1063/1.2211767
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发表时间：
2006-06-01
期刊：
影响因子：
2.9
通讯作者：
Goldbeter, A
中科院分区：
文献类型：
--
作者：
Gonze, D;Goldbeter, A
昼夜节律，其特征在于约24小时的周期，是在分子水平上自主产生的最普遍的生物节律。昼夜节律振荡的核心分子机制依赖于蛋白质对其自身基因表达的负调控。确定性模型解释了自主昼夜节律振荡的发生，它们被明暗周期夹带，以及它们被光脉冲相移。这些模型的随机版本考虑了当参与调节机制的分子数量较低时出现的分子波动。随机模型的数值模拟表明，强大的昼夜节律振荡已经可以发生有限数量的mRNA和蛋白质分子，在几十和几百的范围内，分别。各种因素影响昼夜节律振荡相对于分子噪声的鲁棒性。除了增加分子的数量，夹带的光暗周期，并在镇压协同增强鲁棒性，而接近的分叉点导致不太强大的振荡。另一个似乎对昼夜节律的连贯性至关重要的参数是抑制蛋白与时钟基因启动子的结合/解结合速率。细胞间耦合进一步增加了昼夜节律振荡的鲁棒性。
Circadian rhythms, characterized by a period of about 24 h, are the most widespread biological rhythms generated autonomously at the molecular level. The core molecular mechanism responsible for circadian oscillations relies on the negative regulation exerted by a protein on the expression of its own gene. Deterministic models account for the occurrence of autonomous circadian oscillations, for their entrainment by light-dark cycles, and for their phase shifting by light pulses. Stochastic versions of these models take into consideration the molecular fluctuations that arise when the number of molecules involved in the regulatory mechanism is low. Numerical simulations of the stochastic models show that robust circadian oscillations can already occur with a limited number of mRNA and protein molecules, in the range of a few tens and hundreds, respectively. Various factors affect the robustness of circadian oscillations with respect to molecular noise. Besides an increase in the number of molecules, entrainment by light-dark cycles, and cooperativity in repression enhance robustness, whereas the proximity of a bifurcation point leads to less robust oscillations. Another parameter that appears to be crucial for the coherence of circadian rhythms is the binding/unbinding rate of the inhibitory protein to the promoter of the clock gene. Intercellular coupling further increases the robustness of circadian oscillations.