RT Journal Article SR Electronic T1 Effects of mutation and selection on plasticity of TDH3 promoter activity in Saccharomyces cerevisiae JF bioRxiv FD Cold Spring Harbor Laboratory SP 173344 DO 10.1101/173344 A1 Fabien Duveau A1 David C. Yuan A1 Brian P.H. Metzger A1 Andrea Hodgins-Davis A1 Patricia J. Wittkopp YR 2017 UL http://biorxiv.org/content/early/2017/08/08/173344.abstract AB Phenotypic plasticity is an evolvable property of biological systems that can arise from environment-specific regulation of gene expression. To better understand the evolutionary and molecular mechanisms that give rise to plasticity in gene expression, we quantified the effects of 235 single nucleotide mutations in the Saccharomyces cerevisiae TDH3 promoter (PTDH3) on the activity of this promoter in media containing glucose, galactose, or glycerol as a carbon source. We found that the distributions of mutational effects differed among environments because many mutations altered the plastic response exhibited by the wild type allele. Comparing the effects of these mutations to the effects of 30 PTDH3 polymorphisms on expression plasticity in the same environments provided evidence of natural selection acting to prevent the plastic response in PTDH3 activity between glucose and galactose from becoming larger. The largest changes in expression plasticity were observed between fermentable (glucose or galactose) and nonfermentable (glycerol) carbon sources and were caused by mutations located in the RAP1 and GCR1 transcription factor binding sites. Mutations altered expression plasticity most frequently between the two fermentable environments, however, with mutations causing significant changes in plasticity between glucose and galactose distributed throughout the promoter, suggesting they might affect chromatin structure. Taken together, these results provide insight into the molecular mechanisms underlying gene-by-environment interactions affecting gene expression as well as the evolutionary dynamics affecting natural variation in plasticity of gene expression.Significance Statement From seasonal variation in the color of butterfly wings to trees bending toward the light, organisms often change in response to their environment. These changes, known as phenotypic plasticity, can result from differences in how genes are expressed among environments. Mutations causing environment-specific changes in gene expression provide raw material for phenotypic plasticity, but their frequency, effect size and direction of effects among environments are not well understood. This study shows that mutations in the promoter of a yeast metabolic gene often display environment-dependent effects on gene expression and that these environment-dependent effects have been shaped by selection in natural populations.