Reduced models of the circadian oscillators in Neurospora crassa and Drosophila melanogaster illustrate mechanistic similarities.

Reduced models of the circadian oscillators in Neurospora crassa and Drosophila melanogaster illustrate mechanistic similarities.
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粗糙脉孢菌和果蝇的昼夜节律振荡器的简化模型说明了机制上的相似性。

DOI:
10.1089/153623103322637661
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发表时间:
2003
期刊:
Omics : a journal of integrative biology.
影响因子:
--
通讯作者:
Byrne,JohnH
Byrne,JohnH
中科院分区:
--
文献类型:
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作者:
Smolen,Paul;Baxter,DouglasA;Byrne,JohnH

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我们已经开发了一个简化的模型,代表反馈循环的转录调控的昼夜节律inNeurospora crassa。该模型包含两个时滞微分方程 描述了两个核心基因产物FRQ和WCC的动态。在负反馈环中,FRQ蛋白通过结合白领复合物(WCC)来抑制FRQ转录,该白领复合物由以下组成: WC-1和WC-2蛋白。在正反馈循环中,WCC间接增强了自身的形成。该模型模拟昼夜节律振荡,光夹带,和相位响应曲线(PRC)类似 实验性的PRC。脉孢菌模型实际上与描述果蝇昼夜节律产生的模型相同,说明了这些不同生物体的节律产生 共享重要的机械元素。显着的动态差异时,发现这两个模型的参数空间进行了探索,以分析稳定状态的振荡和分叉的变化。 用吉莱斯皮算法模拟了分子数的随机波动。模拟了昼夜节律振荡和对光的夹带,平均存在<80个分子的FRQ和WCC。 模拟结果表明,在脉孢菌和果蝇中,只有负反馈回路是昼夜振荡所必需的。类似的模型可能有助于理解昼夜节律机制 在哺乳动物和其他生物中。
We have developed a reduced model representing feedback loops of transcriptional regulation underlying circadian rhythms inNeurospora crassa. The model contains two delay differential equations that describe the dynamics of two core gene products, FRQ and WCC. In a negative feedback loop, FRQ protein repressesfrqtranscription by binding the white-collar complex (WCC), which consists of the WC-1 and WC-2 proteins. In a positive feedback loop, WCC indirectly enhances its own formation. The model simulates circadian oscillations, light entrainment, and a phase-response curve (PRC) similar to experimental PRCs. TheNeurosporamodel is virtually identical to a model describingDrosophilacircadian rhythm generation, illustrating that rhythm generation in these divergent organisms shares important mechanistic elements. Significant dynamic differences were found when the parameter spaces of both models were explored to analyze changes in oscillations and bifurcations to steady states. Stochastic fluctuations in molecule numbers were simulated with the Gillespie algorithm. Circadian oscillations and entrainment to light were simulated with <80 molecules of FRQ and WCC present on average. Simulations suggest that in bothNeurosporaandDrosophila, only the negative feedback loop is essential for circadian oscillations. Similar models may aid understanding of circadian mechanisms in mammals and other organisms.