title: Stochastic signalling rewires the interaction map of a multiple feedback network during yeast evolution.
abstract: During evolution, genetic networks are rewired through strengthening or weakening their interactions to develop new regulatory schemes. In the galactose network, the GAL1/GAL3 paralogues and the GAL2 gene enhance their own expression mediated by the Gal4p transcriptional activator. The wiring strength in these feedback loops is set by the number of Gal4p binding sites. Here we show using synthetic circuits that multiplying the binding sites increases the expression of a gene under the direct control of an activator, but this enhancement is not fed back in the circuit. The feedback loops are rather activated by genes that have frequent stochastic bursts and fast RNA decay rates. In this way, rapid adaptation to galactose can be triggered even by weakly expressed genes. Our results indicate that nonlinear stochastic transcriptional responses enable feedback loops to function autonomously, or contrary to what is dictated by the strength of interactions enclosing the circuit.
authors.affiliation: Biozentrum, University of Basel, Klingelbergstrasse 50/70, Basel 4056, Switzerland.
authors.forename: Chieh
authors.initials: C
authors.lastname: Hsu
authors.forename: Simone
authors.initials: S
authors.lastname: Scherrer
authors.forename: Antoine
authors.initials: A
authors.lastname: Buetti-Dinh
authors.forename: Prasuna
authors.initials: P
authors.lastname: Ratna
authors.forename: Julia
authors.initials: J
authors.lastname: Pizzolato
authors.forename: Vincent
authors.initials: V
authors.lastname: Jaquet
authors.forename: Attila
authors.initials: A
authors.lastname: Becskei
mesh_terms: D001665:Binding Sites; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D019143:Evolution, Molecular; D005686:Galactokinase / Q000235:genetics / Q000378:metabolism; D005690:Galactose / Q000378:metabolism*; D053263:Gene Regulatory Networks; D009004:Monosaccharide Transport Proteins / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013269:Stochastic Processes; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D004268:DNA-Binding Proteins; C106901:GAL2 protein, S cerevisiae; C052130:GAL4 protein, S cerevisiae; C099289:Gal3 protein, S cerevisiae; D009004:Monosaccharide Transport Proteins; D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C524219:GAL1 protein, S cerevisiae; D005686:Galactokinase; D005690:Galactose