title: Buffered Qualitative Stability explains the robustness and evolvability of transcriptional networks.
abstract: The gene regulatory network (GRN) is the central decision-making module of the cell. We have developed a theory called Buffered Qualitative Stability (BQS) based on the hypothesis that GRNs are organised so that they remain robust in the face of unpredictable environmental and evolutionary changes. BQS makes strong and diverse predictions about the network features that allow stable responses under arbitrary perturbations, including the random addition of new connections. We show that the GRNs of E. coli, M. tuberculosis, P. aeruginosa, yeast, mouse, and human all verify the predictions of BQS. BQS explains many of the small- and large-scale properties of GRNs, provides conditions for evolvable robustness, and highlights general features of transcriptional response. BQS is severely compromised in a human cancer cell line, suggesting that loss of BQS might underlie the phenotypic plasticity of cancer cells, and highlighting a possible sequence of GRN alterations concomitant with cancer initiation.
authors.affiliation: College of Life Sciences, University of Dundee, Dundee, United Kingdom l.albergante@dundee.ac.uk.
authors.forename: Luca
authors.initials: L
authors.lastname: Albergante
authors.affiliation: College of Life Sciences, University of Dundee, Dundee, United Kingdom j.j.blow@dundee.ac.uk.
authors.forename: J Julian
authors.initials: JJ
authors.lastname: Blow
authors.affiliation: College of Life Sciences, University of Dundee, Dundee, United Kingdom School of Engineering, Physics and Mathematics, University of Dundee, Dundee, United Kingdom t.newman@dundee.ac.uk.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Newman
mesh_terms: D000818:Animals; D003198:Computer Simulation; D003713:Dendritic Cells / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics; D019143:Evolution, Molecular; D005786:Gene Expression Regulation / Q000235:genetics*; D053263:Gene Regulatory Networks / Q000235:genetics*; D006801:Humans; D020014:K562 Cells; D051379:Mice; D008957:Models, Genetic; D009169:Mycobacterium tuberculosis / Q000235:genetics; D009369:Neoplasms / Q000235:genetics; D011550:Pseudomonas aeruginosa / Q000235:genetics; D015203:Reproducibility of Results; D015398:Signal Transduction / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D015003:Yeasts / Q000235:genetics
chemical_list: D014157:Transcription Factors
keywords: antibiotics resistance; cancer; evolvability; gene regulatory network; robustness; systems biology