Phosphorelays are signal transduction circuits that combine four different phosphorylatable protein domains for sensing environmental changes and use that information to adjust cellular metabolism to the new conditions in the milieu. Five alternative circuit architectures account for more than 99% of all phosphorelay operons annotated in over 9000 fully sequenced genomes, with one of those architectures accounting for more than 72% of all cases. Here we asked if there are biological design principles that explain the selection of preferred phosphorelay architectures in nature and what might those principles be. We created several types of data-driven mathematical models for the alternative phosphorelay architectures, exploring the dynamic behavior of the circuits in concentration and parameter space, both analytically and through over 10^8 numerical simulations. We compared the behavior of architectures with respect to signal amplification, speed and robustness of the response, noise in the response, and transmission of environmental information to the cell. Clustering analysis of massive Monte Carlo simulations suggests that either information transmission or metabolic cost could be important in selecting the architecture of the phosphorelay. A more detailed study using models of kinetically well characterized phosphorelays (Spo0 of Bacillus subtilis and Sln1-Ypd1-Ssk1-Skn7 of Saccharomyces cerevisiae) shows that information transmission is maximized by the natural architecture of the phosphorelay. In view of this we analyze seventeen additional phosphorelays, for which protein abundance is available but kinetic parameters are not. The architectures of 16 of these are also consistent with maximization of information transmission. Our results highlight the complexity of the genotype (architecture, parameter values, and protein abundance) to phenotype (physiological output of the circuit) mapping in phosphorelays. The results also suggest that maximizing information transmission through the circuit is important in the selection of natural circuit genotypes.

中文翻译：

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哪些因素会影响本机磷光体结构的选择？

磷光体是信号转导电路，结合了四个不同的可磷酸化蛋白结构域，用于感知环境变化，并使用该信息将细胞代谢调整到环境中的新条件。在9000多个完全测序的基因组中，五种可供选择的电路体系结构占注释的所有磷光体操纵子的99％以上，其中一种体系结构占所有情况的72％以上。在这里，我们问是否有生物学设计原理可以解释自然界中首选的磷灰胶结构的选择以及这些原理可能是什么。我们为替代磷光体结构创建了几种类型的数据驱动数学模型，探讨了浓度和参数空间中电路的动态行为，在分析上和通过超过10 ^ 8的数值模拟。我们比较了架构在信号放大，响应速度和鲁棒性，响应中的噪声以及环境信息向电池传输方面的行为。大规模蒙特卡洛模拟的聚类分析表明，信息传递或代谢成本可能对选择磷光体的结构很重要。使用动力学特征良好的磷光体模型（枯草芽孢杆菌的Spo0和酿酒酵母的Sln1-Ypd1-Ssk1-Skn7）的模型进行的更详细的研究表明，磷光体的自然结构可以最大程度地提高信息传递的效率。有鉴于此，我们分析了另外17种磷光体，其中蛋白质丰度可用，但动力学参数却不可用。其中的16种架构也与信息传输的最大化相一致。我们的研究结果突出了从基因型（结构，参数值和蛋白质丰度）到表型（电路的生理输出）的复杂性。结果还表明，在选择自然电路基因型时，最大化通过电路的信息传输非常重要。