Natural variation in non-coding regions underlying phenotypic diversity in budding yeast

Sci Rep. 2016 Feb 22;6:21849. doi: 10.1038/srep21849.


Linkage mapping studies in model organisms have typically focused their efforts in polymorphisms within coding regions, ignoring those within regulatory regions that may contribute to gene expression variation. In this context, differences in transcript abundance are frequently proposed as a source of phenotypic diversity between individuals, however, until now, little molecular evidence has been provided. Here, we examined Allele Specific Expression (ASE) in six F1 hybrids from Saccharomyces cerevisiae derived from crosses between representative strains of the four main lineages described in yeast. ASE varied between crosses with levels ranging between 28% and 60%. Part of the variation in expression levels could be explained by differences in transcription factors binding to polymorphic cis-regulations and to differences in trans-activation depending on the allelic form of the TF. Analysis on highly expressed alleles on each background suggested ASN1 as a candidate transcript underlying nitrogen consumption differences between two strains. Further promoter allele swap analysis under fermentation conditions confirmed that coding and non-coding regions explained aspartic and glutamic acid consumption differences, likely due to a polymorphism affecting Uga3 binding. Together, we provide a new catalogue of variants to bridge the gap between genotype and phenotype.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Aspartate-Ammonia Ligase / genetics*
  • Aspartate-Ammonia Ligase / metabolism
  • Base Sequence
  • Chimera
  • Crosses, Genetic
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Gene Expression Regulation, Fungal*
  • Genetic Association Studies
  • Genetic Variation
  • Genome, Fungal*
  • Inheritance Patterns
  • Nitrogen / metabolism
  • Open Reading Frames
  • Promoter Regions, Genetic*
  • Quantitative Trait Loci
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / genetics*
  • Saccharomyces cerevisiae Proteins / metabolism
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism


  • ASN1 protein, S cerevisiae
  • DNA-Binding Proteins
  • Saccharomyces cerevisiae Proteins
  • Transcription Factors
  • UGA3 protein, S cerevisiae
  • Aspartate-Ammonia Ligase
  • Nitrogen