Tkacik Gasper, Callan Curtis G, Bialek William
Joseph Henry Laboratories of Physics, Princeton University, Princeton, New Jersey 08544, USA.
Phys Rev E Stat Nonlin Soft Matter Phys. 2008 Jul;78(1 Pt 1):011910. doi: 10.1103/PhysRevE.78.011910. Epub 2008 Jul 21.
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.
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。这些蛋白质进而调节其控制下的基因的表达水平，有时需要执行整合多个输入并影响多个基因的重要计算。同时，即使输入保持固定，由于系统中的内在噪声，受调控基因的活性也会波动，而这种噪声必然会从根本上限制任何基因计算的可靠性。在这里，我们使用信息论来形式化在存在物理上现实的噪声源的情况下简单遗传调控元件中的信息传输概念。系统地探索了这种“信道容量”对噪声参数、协同性和产生信号分子的成本的依赖性。我们发现，在最近体内测量所探究的参数范围内，应该能够实现高于一位的容量。当然，人们普遍认为基因调控元件为了正常发挥功能，必须具有至少一位的容量。我们分析的核心要点是证明具有现实参数的噪声基因转录的简单物理模型确实能够实现这种容量：这并非显而易见。我们还证明了容量显著大于一位是可能的，因此转录调控不必局限于简单的“开 - 关”组件。实际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研究的范围。
