Fundamental limits on the suppression of molecular fluctuations.
Fundamental limits on the suppression of molecular fluctuations.
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负反馈在生物过程中很常见，可以提高系统对内部和外部扰动的稳定性。但在分子水平上，控制回路总是涉及单个分子随机产生和死亡的有限速率的信号传导步骤。通过开发将控制和信息理论与物理化学相结合的数学工具，我们表明，对这些速率看似温和的限制对抑制分子波动的能力造成了严重限制。具体来说，丰度的最小标准偏差随着信号事件数量的四次根而减小，使得提高准确性的成本异常昂贵。我们的结果是根据实验观察结果制定的，现有数据表明，当噪声抑制至关重要时，细胞会使用强力，例如每个细胞周期转录调节基因数万次。该理论挑战了关于生化准确性的传统观念，并提出了一种严格分析特征不良的生物系统的方法。
Negative feedback is common in biological processes and can increase a system’s stability to internal and external perturbations. But at the molecular level, control loops always involve signaling steps with finite rates for random births and deaths of individual molecules. By developing mathematical tools that merge control and information theory with physical chemistry we show that seemingly mild constraints on these rates place severe limits on the ability to suppress molecular fluctuations. Specifically, the minimum standard deviation in abundances decreases with the quartic root of the number of signaling events, making it extraordinarily expensive to increase accuracy. Our results are formulated in terms of experimental observables, and existing data show that cells use brute force when noise suppression is essential, e.g. transcribing regulatory genes 10,000s of times per cell cycle. The theory challenges conventional beliefs about biochemical accuracy and presents an approach to rigorously analyze poorly characterized biological systems.
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影响因子：
64.5
作者：
TOMIZAWA, J
通讯作者：
TOMIZAWA, J
影响因子：
9.9
作者：
Dublanche, Yann;Michalodimitrakis, Konstantinos;Serrano, Luis
通讯作者：
Serrano, Luis
影响因子：
16
作者：
Barkai, Naama;Shilo, Ben-Zion
通讯作者：
Shilo, Ben-Zion
影响因子：
6.8
作者：
Martins, Nuno C.;Dahleh, Munther A.
通讯作者：
Dahleh, Munther A.
DOI：
10.1073/pnas.0806077105
发表时间：
2008-08-26
影响因子：
11.1
作者：
Tkacik, Gasper;Callan, Curtis G., Jr.;Bialek, William
通讯作者：
Bialek, William