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.
复制标题
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
复制
发表时间:
2003
期刊:
影响因子:
--
通讯作者:
Byrne,JohnH
中科院分区:
文献类型:
--
作者:
Smolen,Paul;Baxter,DouglasA;Byrne,JohnH
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.