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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Ultrasensitivity and noise propagation in a synthetic transcriptional cascade
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Ultrasensitivity and noise propagation in a synthetic transcriptional cascade

机译：合成转录级联反应中的超敏性和噪声传播

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摘要

The precise nature of information flow through a biological network, which is governed by factors such as response sensitivities and noise propagation, greatly affects the operation of biological systems. Quantitative analysis of these properties is often difficult in naturally occurring systems but can be greatly facilitated by studying simple synthetic networks. Here, we report the construction of synthetic transcriptional cascades comprising one, two, and three repression stages. These model systems enable us to analyze sensitivity and noise propagation as a function of network complexity. We demonstrate experimentally steady-state switching behavior that becomes sharper with longer cascades. The regulatory mechanisms that confer this ultrasensitive response both attenuate and amplify phenotypical variations depending on the system's input conditions. Although noise attenuation allows the cascade to act as a low-pass filter by rejecting short-lived perturbations in input conditions, noise amplification results in loss of synchrony among a cell population. The experimental results demonstrating the above network properties correlate well with simulations of a simple mathematical model of the system.
机译：通过生物网络的信息流的精确性质受诸如响应敏感性和噪声传播等因素支配，极大地影响了生物系统的运行。这些特性的定量分析在自然发生的系统中通常很困难，但通过研究简单的合成网络可以大大简化这些特性。在这里，我们报告了包含一个，两个和三个阻抑阶段的合成转录级联的构建。这些模型系统使我们能够分析灵敏度和噪声传播与网络复杂度的关系。我们演示了实验性的稳态开关行为，随着级联时间的延长，这种行为会变得更加尖锐。根据系统的输入条件，赋予这种超灵敏响应的调节机制会减弱和放大表型变异。尽管噪声衰减通过拒绝输入条件下的短暂扰动而使级联充当低通滤波器，但噪声放大会导致细胞群体之间失去同步。证明上述网络特性的实验结果与系统的简单数学模型的仿真密切相关。

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