Transcription fluctuation effects on biochemical oscillations.

Transcription fluctuation effects on biochemical oscillations.
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DOI:
10.1371/journal.pone.0060938
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Nakanishi H
Nakanishi H
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Nishino R;Sakaue T;Nakanishi H

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有些生化系统表现出振荡现象。它们通常由具有抑制性转录调节的反馈环组成。与普通化学系统相比,这种生化系统具有独特的特征:i)所涉及的分子数量很小,ii)在细胞中通常只有几个基因,具有有限的调节时间。由于这些特征引起的波动,系统行为可能与确定性速率方程的行为完全不同,因为速率方程忽略了分子波动,因此仅在无限分子数限制下是精确的。Gonze等人(2002)通过引入系统大小的尺度参数研究了自由运行的昼夜节律系统的分子波动。然而,他们只考虑第一种效应,假设基因过程足够快,第二种效应可以忽略不计,但这还没有得到系统的检验。在这里,我们研究由于有限的基因调控时间的波动效应,通过引入一个新的尺度参数,我们采取从基因的核蛋白的解结合时间。我们专注于由于小分子数的波动可以忽略不计的情况。在Gonze等人研究的同一系统的模拟中,我们发现该系统对转录调控的波动出乎意料地敏感,即使在调控时间尺度为30 s左右时,振荡周期也在30 min左右波动,甚至小于其昼夜节律周期的1/1000。我们还证明了在小范围内,振荡周期和振幅的分布宽度与相关时间成比例。周期的相对起伏约为振幅的一半,即周期比振幅更稳定。
Some biochemical systems show oscillation. They often consist of feedback loops with repressive transcription regulation. Such biochemical systems have distinctive characteristics in comparison with ordinary chemical systems: i) numbers of molecules involved are small, ii) there are typically only a couple of genes in a cell with a finite regulation time. Due to the fluctuations caused by these features, the system behavior can be quite different from the one by deterministic rate equations, because the rate equations ignore molecular fluctuations and thus are exact only in the infinite molecular number limit. The molecular fluctuations on a free-running circadian system have been studied by Gonze et al. (2002) by introducing a scale parameter for the system size. They consider, however, only the first effect, assuming that the gene process is fast enough for the second effect to be ignored, but this has not been examined systematically yet. Here we study fluctuation effects due to the finite gene regulation time by introducing a new scale parameter , which we take as the unbinding time of a nuclear protein from the gene. We focus on the case where the fluctuations due to small molecular numbers are negligible. In simulations on the same system studied by Gonze et al., we find the system is unexpectedly sensitive to the fluctuation in the transcription regulation; the period of oscillation fluctuates about 30 min even when the regulation time scale is around 30 s, that is even smaller than 1/1000 of its circadian period. We also demonstrate that the distribution width for the oscillation period and amplitude scales with , and the correlation time scales with in the small regime. The relative fluctuations for the period are about half of that for the amplitude, namely, the periodicity is more stable than the amplitude.
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