Li Qianshu, Lang Xiufeng
School of Chemical Engineering and the Environment, Beijing Institute of Technology, Beijing, China. qsli@bit
Biophys J. 2008 Mar 15;94(6):1983-94. doi: 10.1529/biophysj.107.109611. Epub 2007 Nov 9.
Circadian rhythmic processes, mainly regulated by gene expression at the molecular level, have inherent stochasticity. Their robustness or resistance to internal noise has been extensively investigated by most of the previous studies. This work focuses on the constructive roles of internal noise in a reduced Drosophila model, which incorporates negative and positive feedback loops, each with a time delay. It is shown that internal noise sustains reliable oscillations with periods close to 24 h in a region of parameter space, where the deterministic kinetics would evolve to a stable steady state. The amplitudes of noise-sustained oscillations are significantly affected by the variation of internal noise level, and the best performance of the oscillations could be found at an optimal noise intensity, indicating the occurrence of intrinsic coherence resonance. In the oscillatory region of the deterministic model, the coherence of noisy circadian oscillations is suppressed by internal noise, while the period remains nearly constant over a large range of noise intensity, demonstrating robustness of the Drosophila model for circadian rhythms to intrinsic noise. In addition, the effects of time delay in the positive feedback on the oscillations are also investigated. It is found that the time delay could efficiently tune the performance of the noise-sustained oscillations. These results might aid understanding of the exploitation of intracellular noise in biochemical and genetic regulatory systems.
昼夜节律过程主要在分子水平上受基因表达调控,具有内在的随机性。先前的大多数研究都广泛探讨了它们的稳健性或对内部噪声的抗性。这项工作聚焦于在一个简化的果蝇模型中内部噪声的建设性作用,该模型包含负反馈和正反馈回路,且每个回路都有时间延迟。研究表明,在参数空间的一个区域内,内部噪声能维持周期接近24小时的可靠振荡,而在该区域确定性动力学将演变为稳定的稳态。噪声维持振荡的幅度受内部噪声水平变化的显著影响,并且在最佳噪声强度下能发现振荡的最佳性能,这表明存在内在相干共振。在确定性模型的振荡区域,内部噪声会抑制有噪声的昼夜振荡的相干性,而在较大范围的噪声强度内周期几乎保持不变,这证明了果蝇昼夜节律模型对内在噪声的稳健性。此外,还研究了正反馈中的时间延迟对振荡的影响。研究发现,时间延迟可以有效地调节噪声维持振荡的性能。这些结果可能有助于理解生化和遗传调控系统中细胞内噪声的利用。