Ground state robustness as an evolutionary design principle in signaling networks

  • 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 stronglThe 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 index. Moreover, depending on topological features, the maintenance of robustness differs when networks are faced with structural perturbations. This structural off-state robustness, defined as the average kinetic robustness of a network’s neighborhood, turns out to be useful since some structural features are neutral towards kinetic robustness, but show up to be supporting against structural perturbations. Among these are a low connectivity, a high divergence and a low path sum. All results are tested against real signaling networks obtained from databases. The analysis suggests that ground state robustness may serve as a rationale for some structural peculiarities found in intracellular signaling networks.show moreshow less

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Metadaten
Author:Önder Kartal, Oliver Ebenhöh
URN:urn:nbn:de:kobv:517-opus-44982
Series (Serial Number):Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe, ISSN 1866-8372 (paper 130)
Document Type:Postprint
Language:English
Date of Publication (online):2010/07/16
Year of Completion:2009
Publishing Institution:Universität Potsdam
Release Date:2010/07/16
Tag:Cell; Complex networks; Motifs; Organization; Transduction
Source:PLoS one 4 (2009), 12, Art. e8001, DOI: 10.1371/ journal.pone.0008001
Organizational units:Mathematisch-Naturwissenschaftliche Fakultät / Institut für Biochemie und Biologie
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
Licence (English):License LogoCreative Commons - Attribution 3.0 unported
Notes extern:
The article was originally published by PUBLIC LIBRARY SCIENCE:
PLoS one. - 4 (2009), 12, Art. e8001 (8 S.)
ISSN 1932-6203
DOI 10.1371/journal.pone.0008001