Kollmann Markus, Løvdok Linda, Bartholomé Kilian, Timmer Jens, Sourjik Victor
Institut für Physik, Universität Freiburg, Hermann-Herder-Str. 3, D-79104 Freiburg, Germany.
Nature. 2005 Nov 24;438(7067):504-7. doi: 10.1038/nature04228.
Cellular biochemical networks have to function in a noisy environment using imperfect components. In particular, networks involved in gene regulation or signal transduction allow only for small output tolerances, and the underlying network structures can be expected to have undergone evolution for inherent robustness against perturbations. Here we combine theoretical and experimental analyses to investigate an optimal design for the signalling network of bacterial chemotaxis, one of the most thoroughly studied signalling networks in biology. We experimentally determine the extent of intercellular variations in the expression levels of chemotaxis proteins and use computer simulations to quantify the robustness of several hypothetical chemotaxis pathway topologies to such gene expression noise. We demonstrate that among these topologies the experimentally established chemotaxis network of Escherichia coli has the smallest sufficiently robust network structure, allowing accurate chemotactic response for almost all individuals within a population. Our results suggest that this pathway has evolved to show an optimal chemotactic performance while minimizing the cost of resources associated with high levels of protein expression. Moreover, the underlying topological design principles compensating for intercellular variations seem to be highly conserved among bacterial chemosensory systems.
细胞生化网络必须在存在不完美组件的嘈杂环境中发挥作用。特别是，参与基因调控或信号转导的网络仅允许很小的输出容差，并且可以预期其潜在的网络结构已经历进化以实现对扰动的固有鲁棒性。在这里，我们结合理论和实验分析来研究细菌趋化性信号网络的最优设计，细菌趋化性信号网络是生物学中研究最深入的信号网络之一。我们通过实验确定趋化性蛋白表达水平的细胞间变化程度，并使用计算机模拟来量化几种假设的趋化性途径拓扑结构对这种基因表达噪声的鲁棒性。我们证明，在这些拓扑结构中，实验确定的大肠杆菌趋化性网络具有最小的足够鲁棒的网络结构，使得群体中的几乎所有个体都能进行准确的趋化反应。我们的结果表明，该途径已经进化以展现出最优的趋化性能，同时将与高水平蛋白质表达相关的资源成本降至最低。此外，补偿细胞间变化的潜在拓扑设计原则在细菌化学感应系统中似乎高度保守。
