预测遗传开关对噪声的非对称响应
Predicting the asymmetric response of a genetic switch to noise
摘要：
我们提出了一个简单的分析工具，它给出了一个近似的洞察到非线性系统的平稳行为的影响，从一个主导源，例如，动力学方程描述的遗传开关与浓度的一个基板上下波动的恒定平均值。所提出的方法允许预测的非对称响应的遗传开关噪声，所产生的噪声引起的移动的稳态。该方法已被测试的乳糖操纵子调控网络的示例模型：一个减少Yildirim-Mackey模型与波动的细胞外乳糖浓度。我们计算分析的系统的定态在噪声的存在下的移动。分析计算的结果与数值模拟结果的噪声系统是非常一致的。模拟结果表明，基本的生化反应的动力学结构保护乳糖利用机制的双稳态环境波动。我们还表明，在噪声引起的稳态移动的后果，波动的存在下稳定的系统的行为在一个选择性的方式：虽然外在的噪声促进，在一定程度上，关闭乳糖代谢，相同的噪声阻止它打开。
英文摘要：
We present a simple analytical tool which gives an approximate insight into the stationary behavior of nonlinear systems undergoing the influence of a weak and rapid noise from one dominating source, e.g. the kinetic equations describing a genetic switch with the concentration of one substrate fluctuating around a constant mean. The proposed method allows for predicting the asymmetric response of the genetic switch to noise, arising from the noise-induced shift of stationary states. The method has been tested on an example model of the lac operon regulatory network: a reduced Yildirim-Mackey model with fluctuating extracellular lactose concentration. We calculate analytically the shift of the system's stationary states in the presence of noise. The results of the analytical calculation are in excellent agreement with the results of numerical simulation of the noisy system. The simulation results suggest that the structure of the kinetics of the underlying biochemical reactions protects the bistability of the lactose utilization mechanism from environmental fluctuations. We also show that, in the consequence of the noise-induced shift of stationary states, the presence of fluctuations stabilizes the behavior of the system in a selective way: although the extrinsic noise facilitates, to some extent, switching off the lactose metabolism, the same noise prevents it from switching on.
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