title: Divergence in a master variator generates distinct phenotypes and transcriptional responses.
abstract: Genetic basis of phenotypic differences in individuals is an important area in biology and personalized medicine. Analysis of divergent Saccharomyces cerevisiae strains grown under different conditions revealed extensive variation in response to both drugs (e.g., 4-nitroquinoline 1-oxide [4NQO]) and different carbon sources. Differences in 4NQO resistance were due to amino acid variation in the transcription factor Yrr1. Yrr1(YJM789) conferred 4NQO resistance but caused slower growth on glycerol, and vice versa with Yrr1(S96), indicating that alleles of Yrr1 confer distinct phenotypes. The binding targets of Yrr1 alleles from diverse yeast strains varied considerably among different strains grown under the same conditions as well as for the same strain under different conditions, indicating that distinct molecular programs are conferred by the different Yrr1 alleles. Our results demonstrate that genetic variations in one important control gene (YRR1), lead to distinct regulatory programs and phenotypes in individuals. We term these polymorphic control genes "master variators."
authors.affiliation: Department of Genetics, Stanford University, Stanford, California 94305, USA;
authors.forename: Jennifer E G
authors.initials: JE
authors.lastname: Gallagher
authors.forename: Wei
authors.initials: W
authors.lastname: Zheng
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Rong
authors.forename: Noraliz
authors.initials: N
authors.lastname: Miranda
authors.forename: Zhixiang
authors.initials: Z
authors.lastname: Lin
authors.forename: Barbara
authors.initials: B
authors.lastname: Dunn
authors.forename: Hongyu
authors.initials: H
authors.lastname: Zhao
authors.forename: Michael P
authors.initials: MP
authors.lastname: Snyder
mesh_terms: D015112:4-Nitroquinoline-1-oxide / Q000494:pharmacology; D000483:Alleles; D025141:Drug Resistance, Fungal / Q000235:genetics; D015966:Gene Expression Regulation, Fungal / Q000235:genetics*; D014644:Genetic Variation; D005990:Glycerol / Q000378:metabolism; D009153:Mutagens / Q000494:pharmacology; D010641:Phenotype; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics / Q000254:growth & development / Q000502:physiology*; D013880:Thioredoxin-Disulfide Reductase / Q000235:genetics / Q000378:metabolism
chemical_list: D009153:Mutagens; D015112:4-Nitroquinoline-1-oxide; D013880:Thioredoxin-Disulfide Reductase; D005990:Glycerol
keywords: 4NQO; S. cerevisiae; genetic variation; polymorphism; transcription factor