title: Timing and Variability of Galactose Metabolic Gene Activation Depend on the Rate of Environmental Change.
abstract: Modulation of gene network activity allows cells to respond to changes in environmental conditions. For example, the galactose utilization network in Saccharomyces cerevisiae is activated by the presence of galactose but repressed by glucose. If both sugars are present, the yeast will first metabolize glucose, depleting it from the extracellular environment. Upon depletion of glucose, the genes encoding galactose metabolic proteins will activate. Here, we show that the rate at which glucose levels are depleted determines the timing and variability of galactose gene activation. Paradoxically, we find that Gal1p, an enzyme needed for galactose metabolism, accumulates more quickly if glucose is depleted slowly rather than taken away quickly. Furthermore, the variability of induction times in individual cells depends non-monotonically on the rate of glucose depletion and exhibits a minimum at intermediate depletion rates. Our mathematical modeling suggests that the dynamics of the metabolic transition from glucose to galactose are responsible for the variability in galactose gene activation. These findings demonstrate that environmental dynamics can determine the phenotypic outcome at both the single-cell and population levels.
authors.affiliation: Department of Biosciences, Rice University, Houston, Texas, United States of America.
authors.forename: Truong D
authors.initials: TD
authors.lastname: Nguyen-Huu
authors.affiliation: Department of Mathematics, University of Houston, Houston, Texas, United States of America.
authors.forename: Chinmaya
authors.initials: C
authors.lastname: Gupta
authors.affiliation: Department of Biosciences, Rice University, Houston, Texas, United States of America.
authors.forename: Bo
authors.initials: B
authors.lastname: Ma
authors.affiliation: Department of Mathematics, University of Houston, Houston, Texas, United States of America.
authors.forename: William
authors.initials: W
authors.lastname: Ott
authors.affiliation: Department of Mathematics, University of Houston, Houston, Texas, United States of America; Department of Biology and Biochemistry, University of Houston, Houston, Texas, United States of America.
authors.forename: Krešimir
authors.initials: K
authors.lastname: Josić
authors.affiliation: Department of Biosciences, Rice University, Houston, Texas, United States of America; Institute of Biosciences and Bioengineering, Rice University, Houston, Texas, United States of America.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Bennett
mesh_terms: D000222:Adaptation, Physiological / Q000502:physiology; D019149:Bioreactors / Q000382:microbiology*; D017753:Ecosystem; D005690:Galactose / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D029701:Saccharomyces cerevisiae Proteins; D005947:Glucose; D005690:Galactose