title: Functional modules of sigma factor regulons guarantee adaptability and evolvability.
abstract: The focus of modern molecular biology turns from assigning functions to individual genes towards understanding the expression and regulation of complex sets of molecules. Here, we provide evidence that alternative sigma factor regulons in the pathogen Pseudomonas aeruginosa largely represent insulated functional modules which provide a critical level of biological organization involved in general adaptation and survival processes. Analysis of the operational state of the sigma factor network revealed that transcription factors functionally couple the sigma factor regulons and significantly modulate the transcription levels in the face of challenging environments. The threshold quality of newly evolved transcription factors was reached faster and more robustly in in silico testing when the structural organization of sigma factor networks was taken into account. These results indicate that the modular structures of alternative sigma factor regulons provide P. aeruginosa with a robust framework to function adequately in its environment and at the same time facilitate evolutionary change. Our data support the view that widespread modularity guarantees robustness of biological networks and is a key driver of evolvability.
authors.affiliation: Department of Systems Immunology and Braunschweig Integrated Centre of Systems Biology, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany.
authors.forename: Sebastian C
authors.initials: SC
authors.lastname: Binder
authors.affiliation: Institute for Molecular Bacteriology, TWINCORE GmbH, Center for Clinical and Experimental Infection Research, a joint venture of the Hannover Medical School and the Helmholtz Center for Infection Research, 30265 Hannover, Germany.|Department of Molecular Bacteriology, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany.
authors.forename: Denitsa
authors.initials: D
authors.lastname: Eckweiler
authors.affiliation: Institute for Molecular Bacteriology, TWINCORE GmbH, Center for Clinical and Experimental Infection Research, a joint venture of the Hannover Medical School and the Helmholtz Center for Infection Research, 30265 Hannover, Germany.|Department of Molecular Bacteriology, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Schulz
authors.affiliation: Institute for Molecular Bacteriology, TWINCORE GmbH, Center for Clinical and Experimental Infection Research, a joint venture of the Hannover Medical School and the Helmholtz Center for Infection Research, 30265 Hannover, Germany.|Department of Molecular Bacteriology, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany.
authors.forename: Agata
authors.initials: A
authors.lastname: Bielecka
authors.affiliation: Department of Molecular Bacteriology, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany.
authors.forename: Tanja
authors.initials: T
authors.lastname: Nicolai
authors.affiliation: Department of Chemical Biology, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany.
authors.forename: Raimo
authors.initials: R
authors.lastname: Franke
authors.affiliation: Institute for Molecular Bacteriology, TWINCORE GmbH, Center for Clinical and Experimental Infection Research, a joint venture of the Hannover Medical School and the Helmholtz Center for Infection Research, 30265 Hannover, Germany.|Department of Molecular Bacteriology, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Häussler
authors.affiliation: Department of Systems Immunology and Braunschweig Integrated Centre of Systems Biology, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany.|Institute for Biochemistry, Biotechnology and Bioinformatics, Technische Universität Braunschweig, 38124 Braunschweig, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Meyer-Hermann
mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics*; D015964:Gene Expression Regulation, Bacterial / Q000235:genetics*; D011550:Pseudomonas aeruginosa / Q000235:genetics* / Q000378:metabolism*; D018085:Regulon / Q000235:genetics; D012808:Sigma Factor / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic / Q000235:genetics*
chemical_list: D012808:Sigma Factor