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首页> 外文期刊>PLoS Computational Biology >Stochastic Delay Accelerates Signaling in Gene Networks
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Stochastic Delay Accelerates Signaling in Gene Networks

机译:随机时延加速基因网络中的信号传递

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摘要

The creation of protein from DNA is a dynamic process consisting of numerous reactions, such as transcription, translation and protein folding. Each of these reactions is further comprised of hundreds or thousands of sub-steps that must be completed before a protein is fully mature. Consequently, the time it takes to create a single protein depends on the number of steps in the reaction chain and the nature of each step. One way to account for these reactions in models of gene regulatory networks is to incorporate dynamical delay. However, the stochastic nature of the reactions necessary to produce protein leads to a waiting time that is randomly distributed. Here, we use queueing theory to examine the effects of such distributed delay on the propagation of information through transcriptionally regulated genetic networks. In an analytically tractable model we find that increasing the randomness in protein production delay can increase signaling speed in transcriptional networks. The effect is confirmed in stochastic simulations, and we demonstrate its impact in several common transcriptional motifs. In particular, we show that in feedforward loops signaling time and magnitude are significantly affected by distributed delay. In addition, delay has previously been shown to cause stable oscillations in circuits with negative feedback. We show that the period and the amplitude of the oscillations monotonically decrease as the variability of the delay time increases.
机译:从DNA产生蛋白质是一个动态过程,包括许多反应,例如转录,翻译和蛋白质折叠。这些反应中的每一个都进一步包含数百或数千个子步骤,这些步骤必须在蛋白质完全成熟之前完成。因此,产生单个蛋白质所需的时间取决于反应链中步骤的数量以及每个步骤的性质。解决基因调节网络模型中这些反应的一种方法是纳入动态延迟。但是,产生蛋白质所需的反应的随机性导致等待时间随机分布。在这里,我们使用排队论来研究这种分布式延迟对通过转录调控的遗传网络传播信息的影响。在一个易于分析的模型中,我们发现增加蛋白质生产延迟的随机性可以增加转录网络中的信号传导速度。这种效果在随机模拟中得到了证实,我们证明了它在几种常见转录基序中的影响。特别是,我们表明,在前馈环路中,信令时间和幅度受分布式延迟的影响很大。此外,以前已经证明延迟会在具有负反馈的电路中引起稳定的振荡。我们显示,随着延迟时间的可变性增加,振荡的周期和振幅单调减小。

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