title: The binary response of the GAL/MEL genetic switch of Saccharomyces cerevisiae is critically dependent on Gal80p-Gal4p interaction.
abstract: Studies on the Saccharomyces cerevisiae GAL/MEL genetic switch have revealed that its bistability is dependent on ultrasensitivity that can be altered or abolished by disabling different combinations of nested feedback loops. In contrast, we have previously demonstrated that weakening of the interaction between Gal80p and Gal4p alone is sufficient to abolish the ultrasensitivity (Das Adhikari et al. 2014). Here, we demonstrate that altering the epistatic interaction between Gal80p and Gal4p also abolishes the bistability, and the switch response to galactose becomes graded instead of binary. However, the GAL/MEL switch of wild-type and epistatically altered strains responded in a graded fashion to melibiose. The properties of the epistatically altered strain resemble Kluyveromyces lactis, which separated from the Saccharomyces lineage 100 mya before whole-genome duplication (WGD). Based on the results reported here, we propose that epistatic interactions played a crucial role in the evolution of the fine regulation of S. cerevisiae GAL/MEL switch following WGD.
authors: Laboratory of Molecular Genetics, Department of Bioscience and Bioengineering, Indian Institute of Technology Bombay, Powai, Mumbai 400076, India.
authors: Akshay Kumar
authors: AK
authors: Das Adhikari
authors: Laboratory of Molecular Genetics, Department of Bioscience and Bioengineering, Indian Institute of Technology Bombay, Powai, Mumbai 400076, India jayadeva@iitb.ac.in.
authors: Paike Jayadeva
authors: PJ
authors: Bhat
mesh_terms: D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004843:Epistasis, Genetic; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; C052130:GAL4 protein, S cerevisiae; C055002:GAL80 protein, S cerevisiae; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors
keywords: GAL/MEL switch; bistability; epistasis; evolution; ultrasensitivity