[Deterministic and stochastic models for circadian rhythms].-猫眼课题宝

[昼夜节律的确定性和随机模型]。

DOI：

发表时间：

2003

期刊：

Pathologie et biologie

影响因子：

通讯作者：

中科院分区：

文献类型：

作者：

D. Gonze;J. Halloy;A. Goldbeter

昼夜节律以大约24小时为特征，在几乎所有的生物体中都是通过时钟基因表达的负自动调节而产生的。基于这种遗传调控的确定性模型解释了恒定环境条件下的昼夜振荡(例如，在恒定的黑暗中)，并解释了这些节律被明暗循环缠绕。当时钟mRNA和蛋白质分子数目较少时，有必要采用随机模拟来评估分子噪声对昼夜节律振荡的影响。事实上，如果时钟机制中涉及的分子数量仍然太低，那么基因表达的自动调节机制可能由于波动而不能产生稳定的节奏。我们比较了基于时钟基因负自动调节的模型的确定性和随机性方法。我们通过随机模拟表明，当mRNA和蛋白质分子的最大数量分别为几十个或数百个数量级时，就已经可以发生稳健的昼夜振荡。此外，结果表明，转录过程抑制的协同性增强了昼夜节律的稳健性，而光-暗周期的夹带稳定了振荡的相位。

Circadian rhythms, characterized by a period of about 24h, are generated in nearly all living organisms by the negative autoregulation of clock gene expression. Deterministic models based on this genetic regulation account for circadian oscillations in constant environmental conditions (e.g., in constant darkness) and for entrainment of these rhythms by light-dark cycles. When the number of clock mRNA and protein molecules is low, it is necessary to resort to stochastic simulations to assess the influence of molecular noise on circadian oscillations. Indeed, it is possible that the autoregulatory mechanism of gene expression might not produce stable rhythms due to fluctuations if the number of molecules involved in the clock mechanism remains too low. We have compared the deterministic and stochastic approaches for a model based on the negative autoregulation of a clock gene. We show by means of stochastic simulations that robust circadian oscillations can already occur when the maximum number of mRNA and protein molecules is of the order of a few tens or hundreds, respectively. Furthermore, the results indicate that the cooperativity characterizing the repression of the transcription process strenghtens the robustness of circadian rhythms and that entrainment by light-dark cycles stabilizes the phase of the oscillations.

Dissection of a circadian oscillation into discrete domains.