Divergence in a master variator generates distinct phenotypes and transcriptional responses

  1. Michael P. Snyder1,9
  1. 1Department of Genetics, Stanford University, Stanford, California 94305, USA;
  2. 2Department of Biology, West Virginia University, Morgantown, West Virginia 26506, USA;
  3. 3Keck Biostatistics Resources, Yale University, New Haven, Connecticut 06510, USA;
  4. 4University of Puerto Rico, Aguadilla, Puerto Rico 00604;
  5. 5Biological and Biomedical Sciences Graduate Program, Yale University, New Haven, Connecticut 06520, USA;
  6. 6Program in Computational Biology and Bioinformatics, Yale University School of Medicine, New Haven, Connecticut 06520, USA;
  7. 7Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, Connecticut 06520, USA;
  8. 8Department of Genetics, Yale University School of Medicine, New Haven, Connecticut 06520, USA

    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. Yrr1YJM789 conferred 4NQO resistance but caused slower growth on glycerol, and vice versa with Yrr1S96, 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.”

    Keywords

    Footnotes

    • Received August 18, 2013.
    • Accepted January 13, 2014.

    This article, published in Genes & Development, is available under a Creative Commons License (Attribution-NonCommercial 3.0 Unported), as described at http://creativecommons.org/licenses/by-nc/3.0/.

    | Table of Contents
    OPEN ACCESS ARTICLE

    G&D Most Read

    View all ...

    Life Science Alliance