Divergence of the yeast transcription factor FZF1 affects sulfite resistance

PLoS Genet. 2012;8(6):e1002763. doi: 10.1371/journal.pgen.1002763. Epub 2012 Jun 14.


Changes in gene expression are commonly observed during evolution. However, the phenotypic consequences of expression divergence are frequently unknown and difficult to measure. Transcriptional regulators provide a mechanism by which phenotypic divergence can occur through multiple, coordinated changes in gene expression during development or in response to environmental changes. Yet, some changes in transcriptional regulators may be constrained by their pleiotropic effects on gene expression. Here, we use a genome-wide screen for promoters that are likely to have diverged in function and identify a yeast transcription factor, FZF1, that has evolved substantial differences in its ability to confer resistance to sulfites. Chimeric alleles from four Saccharomyces species show that divergence in FZF1 activity is due to changes in both its coding and upstream noncoding sequence. Between the two closest species, noncoding changes affect the expression of FZF1, whereas coding changes affect the expression of SSU1, a sulfite efflux pump activated by FZF1. Both coding and noncoding changes also affect the expression of many other genes. Our results show how divergence in the coding and promoter region of a transcription factor alters the response to an environmental stress.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Alleles
  • Anion Transport Proteins / genetics*
  • Anion Transport Proteins / metabolism
  • Drug Resistance / genetics
  • Evolution, Molecular
  • Gene Expression Regulation, Fungal* / drug effects
  • Gene Expression Regulation, Fungal* / genetics
  • Genetic Association Studies
  • Genome, Fungal
  • Open Reading Frames
  • Promoter Regions, Genetic
  • Regulatory Sequences, Nucleic Acid
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / genetics*
  • Saccharomyces cerevisiae Proteins / metabolism
  • Species Specificity
  • Sulfites* / metabolism
  • Sulfites* / pharmacology
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism


  • Anion Transport Proteins
  • FZF1 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Ssu1 protein, S cerevisiae
  • Sulfites
  • Transcription Factors