Mechanisms of noise-resistance in genetic oscillators
Mechanisms of noise-resistance in genetic oscillators
复制标题
DOI：
10.1073/pnas.092133899
复制
发表时间：
2002-04-30
影响因子：
11.1
通讯作者：
Leibler, S
中科院分区：
文献类型：
--
作者：
Vilar, JMG;Kueh, HY;Leibler, S
许多生物利用生物钟来保持对日常时间的内部感觉，并相应地调节其行为。这些生物钟大多使用基于正调控元件和负调控元件的细胞内遗传网络。这些“电路”在细胞水平上的集成对其功能和设计施加了强烈的约束。在这里，我们研究了最近提出的模型[Barkai，N。& Leibler，S.（2000）Nature（伦敦），403，267-268]，其仅结合了实验发现的基本元素。我们发现，这种类型的振荡器主要是由两个要素驱动：阻遏蛋白的浓度和激活蛋白与阻遏物形成无活性复合物的动力学。因此，生物钟不需要依赖mRNA动力学来振荡，这使得它特别能抵抗波动。即使当mRNA分子数量的时间平均值低于1时，振荡也可能存在。在某些条件下，这个振荡器不仅能抵抗，而且矛盾的是，还能被内在的生化噪声增强。
A wide range of organisms use circadian clocks to keep internal sense of daily time and regulate their behavior accordingly. Most of these clocks use intracellular genetic networks based on positive and negative regulatory elements. The integration of these "circuits" at the cellular level imposes strong constraints on their functioning and design. Here, we study a recently proposed model [Barkai, N. & Leibler, S. (2000) Nature (London), 403, 267-268] that incorporates just the essential elements found experimentally. We show that this type of oscillator is driven mainly by two elements: the concentration of a repressor protein and the dynamics of an activator protein forming an inactive complex with the repressor. Thus, the clock does not need to rely on mRNA dynamics to oscillate, which makes it especially resistant to fluctuations. Oscillations can be present even when the time average of the number of mRNA molecules goes below one. Under some conditions, this oscillator is not only resistant to but, paradoxically, also enhanced by the intrinsic biochemical noise.