Vilar José M G, Kueh Hao Yuan, Barkai Naama, Leibler Stanislas
Howard Hughes Medical Institute, Department of Molecular Biology and Physics, Princeton University, Princeton, NJ 08544, USA.
Proc Natl Acad Sci U S A. 2002 Apr 30;99(9):5988-92. doi: 10.1073/pnas.092133899. Epub 2002 Apr 23.
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.
各种各样的生物体利用昼夜节律时钟来保持对每日时间的内在感知，并据此调节它们的行为。这些时钟中的大多数都使用基于正负调控元件的细胞内遗传网络。这些“电路”在细胞水平上的整合对其功能和设计施加了严格的限制。在这里，我们研究了一个最近提出的模型[巴尔凯，N. & 莱布勒，S.（2000年）《自然》（伦敦），403，267 - 268]，该模型仅纳入了实验中发现的基本要素。我们表明，这种类型的振荡器主要由两个要素驱动：一种阻遏蛋白的浓度以及一种与阻遏蛋白形成无活性复合物的激活蛋白的动力学。因此，时钟不需要依赖mRNA动力学来振荡，这使其对波动具有特别的抗性。即使mRNA分子数量的时间平均值低于1，振荡也可能存在。在某些条件下，这种振荡器不仅对内在生化噪声具有抗性，而且自相矛盾的是，还会被其增强。
