Information capacity of genetic regulatory elements.
Information capacity of genetic regulatory elements.
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DOI：
10.1103/physreve.78.011910
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发表时间：
2008-07
期刊：
影响因子：
--
通讯作者：
Bialek W
中科院分区：
文献类型：
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作者：
Tkacik G;Callan CG Jr;Bialek W
细胞外部或内部条件的变化通常反映在相关转录因子的浓度上。这些蛋白质反过来调节它们控制下的基因的表达水平，有时需要执行整合几个输入并影响多个基因的重要计算。同时，由于系统中的固有噪声，即使输入保持不变，受调控基因的活动也会波动，这种噪声肯定从根本上限制了任何遗传计算的可靠性。在这里，我们使用信息论来形式化在物理上真实的噪声源存在的情况下，在简单的遗传调控元件中进行信息传递的概念。系统地研究了这种“信道容量”与噪声参数、协作性和制造信号分子的成本的关系。我们发现，在最近的活体测量所探测的参数范围内，应该可以实现比1比特更高的容量。当然，人们普遍认为，基因调控元件必须具有至少一位的容量，才能正常发挥作用。我们分析的中心点是证明，带有真实参数的噪音基因转录的简单物理模型确实可以实现这种能力：这种情况并不是不言而喻的。我们还证明了显著大于1比特的容量是可能的，因此转录调控不需要局限于简单的“开-关”成分。真正的系统是否真的利用了这种更丰富的可能性，这一问题超出了本次调查的范围。
Changes in a cell’s external or internal conditions are usually reflected in the concentrations of the relevant transcription factors. These proteins in turn modulate the expression levels of the genes under their control and sometimes need to perform nontrivial computations that integrate several inputs and affect multiple genes. At the same time, the activities of the regulated genes would fluctuate even if the inputs were held fixed, as a consequence of the intrinsic noise in the system, and such noise must fundamentally limit the reliability of any genetic computation. Here we use information theory to formalize the notion of information transmission in simple genetic regulatory elements in the presence of physically realistic noise sources. The dependence of this “channel capacity” on noise parameters, cooperativity and cost of making signaling molecules is explored systematically. We find that, in the range of parameters probed by recent in vivo measurements, capacities higher than one bit should be achievable. It is of course generally accepted that gene regulatory elements must, in order to function properly, have a capacity of at least one bit. The central point of our analysis is the demonstration that simple physical models of noisy gene transcription, with realistic parameters, can indeed achieve this capacity: it was not self-evident that this should be so. We also demonstrate that capacities significantly greater than one bit are possible, so that transcriptional regulation need not be limited to simple “on-off” components. The question whether real systems actually exploit this richer possibility is beyond the scope of this investigation.