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首页> 外文期刊>International Journal of Quantum Chemistry >Stochastic Models for Circadian Oscillations:Emergence of a Biological Rhythm
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Stochastic Models for Circadian Oscillations:Emergence of a Biological Rhythm

机译：昼夜节律振荡的随机模型：生物节律的出现

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Nearly all living organisms display circadian oscillations characterized by a period close to 24 h.These rhythms originate from the negative autoregulation of gene expression.Deterministic models based on such genetic regulatory processes account for the occurrence of circadian rhythms in constant environmental conditions(e.g.,constant darkness),for entrainment of these rhythms by light-dark cycles,and for their phase-shifting by light pulses.When the numbers of protein and mRNA molecules involved in the oscillations are small,as may occur in cellular conditions,it becomes necessary to resort to stochastic simulations to assess the influence of molecular noise on circadian oscillations.We address the effect of molecular noise by considering the stochastic version of a core deterministic model previously proposed for circadian oscillations of the PER protein and its mRNA in Drosophila.The model is based on cooperative repression of the per gene by the PER protein.Numerical simulations of the stochastic version of the model are performed by means of the Gillespie method.The predictions of the stochastic approach compare well with those of the deterministic model with respect to both sustained oscillations of the limit cycle type and the influence of the proximity from a bifurcation point below which the system evolves to a stable steady state.Stochastic simulations indicate that robust circadian oscillations can emerge at the cellular level,even when the maximum numbers of mRNA and protein molecules involved in the oscillations are of the order of only a few tens or hundreds.The stochastic simulations also reproduce the evolution toward a strange attractor in conditions where an extended version of the deterministic model admits chaotic behavior.These results show how regulatory feedback processes at the cellular level allow the emergence of a coherent biological rhythm out of molecular noise.
机译：几乎所有活生物体都有昼夜节律振荡，周期接近24小时，这些节律源自基因表达的负自调控。基于这种遗传调控过程的确定性模型解释了恒定环境条件下昼夜节律的发生（例如恒定黑暗），以通过明暗循环来夹带这些节律，并通过光脉冲使它们发生相移。当振荡中涉及的蛋白质和mRNA分子的数量较小时（如在细胞条件下可能发生），有必要我们采用随机模拟方法来评估分子噪声对昼夜节律振荡的影响，我们通过考虑先前为果蝇PER蛋白及其mRNA的昼夜节律振荡提出的核心确定性模型的随机版本来解决分子噪声的影响。基于PER蛋白协同抑制每个基因的数值模拟如果模型的随机版本是通过Gillespie方法执行的，那么就极限循环类型的持续振荡以及分叉点的接近性影响而言，随机方法的预测与确定性模型的预测相比较随机模拟表明，即使参与该振荡的mRNA和蛋白质分子的最大数量只有几十个或几十个数量级，也可以在细胞水平上出现强大的生物钟振荡。在确定性模型的扩展版本允许混沌行为的条件下，随机模拟还重现了向奇怪吸引子的演化。这些结果表明，细胞水平的调节反馈过程如何使分子噪声中出现连贯的生物节律。

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