Gene network shaping of inherent noise spectra
Gene network shaping of inherent noise spectra
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DOI：
10.1038/nature04194
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发表时间：
2006-02-02
期刊：
影响因子：
64.8
通讯作者：
Simpson, ML
中科院分区：
文献类型：
--
作者：
Austin, DW;Allen, MS;Simpson, ML
最近的研究表明，分子群体的随机波动对基因调控有影响（1-10）。以前的实验主要是通过测量噪声的大小来研究噪声源或噪声在基因网络中的传播。然而，在理论分析中，我们发现噪声频率含量是由底层基因电路决定的，导致基因电路结构与噪声频率范围之间存在映射（11,12）。从我们之前的研究中得出的一个有趣的预测是，负的自调节将噪声转移到更容易被基因网络过滤掉的更高频率（11）——这一特性可能有助于自调节基元的流行（例如，在40%的大肠杆菌基因中发现了类似的调控）。在这里，我们测量了大肠杆菌生长培养物中的噪声频率含量，并通过展示负自调节介导的频谱移位来验证基因电路结构与噪声光谱之间的联系。我们进一步证明，噪声谱测量提供了基因调控的机制见解，因为基因回路参数的扰动在测量的噪声频率范围内是可识别的。这些结果表明，噪声谱测量可以促进发现新的调节关系。
Recent work demonstrates that stochastic fluctuations in molecular populations have consequences for gene regulation(1-10). Previous experiments focused on noise sources or noise propagation through gene networks by measuring noise magnitudes. However, in theoretical analysis, we showed that noise frequency content is determined by the underlying gene circuits, leading to a mapping between gene circuit structure and the noise frequency range(11,12). An intriguing prediction from our previous studies was that negative autoregulation shifts noise to higher frequencies where it is more easily filtered out by gene networks(11) - a property that may contribute to the prevalence of autoregulation motifs ( for example, found in the regulation of similar to 40% of Escherichia coli genes). Here we measure noise frequency content in growing cultures of E. coli, and verify the link between gene circuit structure and noise spectra by demonstrating the negative autoregulation-mediated spectral shift. We further demonstrate that noise spectral measurements provide mechanistic insights into gene regulation, as perturbations of gene circuit parameters are discernible in the measured noise frequency ranges. These results suggest that noise spectral measurements could facilitate the discovery of novel regulatory relationships.