title: Tuning the range and stability of multiple phenotypic states with coupled positive-negative feedback loops.
abstract: Positive feedback loops can produce multistability, resulting in different phenotypic states. However, many transcription networks contain counteracting positive and negative feedbacks. Here we explore the dynamics of an interlinked positive and negative feedback motif based on the galactose-uptake control system of Saccharomyces cerevisiae modified to make the strength of each feedback externally controllable. Our results show that although the positive feedback loop determines the range of bistability and the width of the regions where intermediate activation is possible, the transition rates between states are mostly sensitive to the negative feedback strength. Thus, our results suggest that the function of the negative loop in this motif is to allow separate tuning of the range and transition rates between phenotypic states. This could enhance fitness by allowing improved matching of the stochastic switching to the frequency of environmental changes.
authors.affiliation: 1] Department of Systems Biology, Harvard Medical School, Boston, Massachusetts 02115, USA [2] Wyss Institute for Biologically Inspired Engineering, 3 Blackfan Circle, Boston, Massachusetts 02115, USA [3] Department of Physics, Universidad de Los Andes, Bogotá 111711, Colombia.
authors.forename: Maier S
authors.initials: MS
authors.lastname: Avendaño
authors.forename: Chad
authors.initials: C
authors.lastname: Leidy
authors.forename: Juan M
authors.initials: JM
authors.lastname: Pedraza
mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics; D001692:Biological Transport; D025461:Feedback, Physiological; D005690:Galactose / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D053263:Gene Regulatory Networks; D056084:Genetic Fitness; D005838:Genotype; D005947:Glucose / Q000378:metabolism; D008954:Models, Biological; D010641:Phenotype; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D029701:Saccharomyces cerevisiae Proteins; D005947:Glucose; D005690:Galactose