ground state robustness as an evolutionary design principle in signaling networks基态的鲁棒性作为一个进化的设计原则在信号网络.pdfVIP

Ground State Robustness as an Evolutionary Design Principle in Signaling Networks ¨ 1,2 ¨ 1,2,3 Onder Kartal *, Oliver Ebenhoh 1 Max Planck Institute of Molecular Plant Physiology, Potsdam-Golm, Germany, 2 Institute of Biochemistry and Biology, University of Potsdam, Potsdam-Golm, Germany, 3 Institute for Complex Systems, University of Aberdeen, Aberdeen, United Kingdom Abstract The ability of an organism to survive depends on its capability to adapt to external conditions. In addition to metabolic versatility and efficient replication, reliable signal transduction is essential. As signaling systems are under permanent evolutionary pressure one may assume that their structure reflects certain functional properties. However, despite promising theoretical studies in recent years, the selective forces which shape signaling network topologies in general remain unclear. Here, we propose prevention of autoactivation as one possible evolutionary design principle. A generic framework for continuous kinetic models is used to derive topological implications of demanding a dynamically stable ground state in signaling systems. To this end graph theoretical methods are applied. The index of the underlying digraph is shown to be a key topological property which determines the so-called kinetic ground state (or off-state) robustness. The kinetic robustness depends solely on the composition of the subdigraph with the strongly connected components, which comprise all positive feedbacks in the network. The component with the highest index in the feedback family is shown to dominate the kinetic robustness of the whole network, whereas relative size and girth of these motifs are emphasized as important determinants of the component