title: Evolution of gene network activity by tuning the strength of negative-feedback regulation.
abstract: Despite the examples of protein evolution via mutations in coding sequences, we have very limited understanding on gene network evolution via changes in cis-regulatory elements. Using the galactose network as a model, here we show how the regulatory promoters of the network contribute to the evolved network activity between two yeast species. In Saccharomyces cerevisiae, we combinatorially replace all regulatory network promoters by their counterparts from Saccharomyces paradoxus, measure the resulting network inducibility profiles, and model the results. Lowering relative strength of GAL80-mediated negative feedback by replacing GAL80 promoter is necessary and sufficient to have high network inducibility levels as in S. paradoxus. This is achieved by increasing OFF-to-ON phenotypic switching rates. Competitions performed among strains with or without the GAL80 promoter replacement show strong relationships between network inducibility and fitness. Our results support the hypothesis that gene network activity can evolve by optimizing the strength of negative-feedback regulation.
authors: 1] Department of Molecular Cellular and Developmental Biology, Yale University, 219 Prospect Street, New Haven, Connecticut 06511, USA [2] Systems Biology Institute, Yale University, 840 West Campus Drive, West Haven, Connecticut 06516, USA.
authors: Weilin
authors: W
authors: Peng
authors: 1] Department of Molecular Cellular and Developmental Biology, Yale University, 219 Prospect Street, New Haven, Connecticut 06511, USA [2] Systems Biology Institute, Yale University, 840 West Campus Drive, West Haven, Connecticut 06516, USA.
authors: Ping
authors: P
authors: Liu
authors: 1] Department of Molecular Cellular and Developmental Biology, Yale University, 219 Prospect Street, New Haven, Connecticut 06511, USA [2] Systems Biology Institute, Yale University, 840 West Campus Drive, West Haven, Connecticut 06516, USA.
authors: Yuan
authors: Y
authors: Xue
authors: 1] Department of Molecular Cellular and Developmental Biology, Yale University, 219 Prospect Street, New Haven, Connecticut 06511, USA [2] Systems Biology Institute, Yale University, 840 West Campus Drive, West Haven, Connecticut 06516, USA [3] Department of Physics, Yale University, 217 Prospect Street, New Haven, Connecticut 06511, USA.
authors: Murat
authors: M
authors: Acar
mesh_terms: D003001:Cloning, Molecular; D019143:Evolution, Molecular; D025461:Feedback, Physiological / Q000187:drug effects; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D005690:Galactose / Q000378:metabolism / Q000494:pharmacology; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects; D053263:Gene Regulatory Networks / Q000187:drug effects; D005800:Genes, Fungal; D005812:Genes, Switch; D056084:Genetic Fitness / Q000187:drug effects; D010641:Phenotype; D011401:Promoter Regions, Genetic; D012440:Saccharomyces / Q000187:drug effects / Q000235:genetics*
chemical_list: D005656:Fungal Proteins; D005690:Galactose