title: Natural variation in non-coding regions underlying phenotypic diversity in budding yeast.
abstract: 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.
authors.affiliation: Millennium Nucleus for Fungal Integrative and Synthetic Biology (MN-FISB), Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Casilla 114-D, Santiago, Chile.
authors.forename: Francisco
authors.initials: F
authors.lastname: Salinas
authors.affiliation: Broad Institute of MIT and Harvard, Cambridge, MA, United States.
authors.forename: Carl G
authors.initials: CG
authors.lastname: de Boer
authors.affiliation: Centro de Estudios en Ciencia y Tecnología de Alimentos (CECTA), Universidad de Santiago de Chile (USACH), Santiago, Chile.
authors.forename: Valentina
authors.initials: V
authors.lastname: Abarca
authors.affiliation: Centro de Estudios en Ciencia y Tecnología de Alimentos (CECTA), Universidad de Santiago de Chile (USACH), Santiago, Chile.|Departamento de Ciencia y Tecnología de los Alimentos, Universidad de Santiago de Chile (USACH), Santiago, Chile.
authors.forename: Verónica
authors.initials: V
authors.lastname: García
authors.affiliation: Centro de Estudios en Ciencia y Tecnología de Alimentos (CECTA), Universidad de Santiago de Chile (USACH), Santiago, Chile.
authors.forename: Mara
authors.initials: M
authors.lastname: Cuevas
authors.affiliation: Centro de Estudios en Ciencia y Tecnología de Alimentos (CECTA), Universidad de Santiago de Chile (USACH), Santiago, Chile.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Araos
authors.affiliation: Millennium Nucleus for Fungal Integrative and Synthetic Biology (MN-FISB), Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Casilla 114-D, Santiago, Chile.
authors.forename: Luis F
authors.initials: LF
authors.lastname: Larrondo
authors.affiliation: Centro de Estudios en Ciencia y Tecnología de Alimentos (CECTA), Universidad de Santiago de Chile (USACH), Santiago, Chile.|Departamento de Ciencia y Tecnología de los Alimentos, Universidad de Santiago de Chile (USACH), Santiago, Chile.
authors.forename: Claudio
authors.initials: C
authors.lastname: Martínez
authors.affiliation: Millennium Nucleus for Fungal Integrative and Synthetic Biology (MN-FISB), Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Casilla 114-D, Santiago, Chile.|Centro de Estudios en Ciencia y Tecnología de Alimentos (CECTA), Universidad de Santiago de Chile (USACH), Santiago, Chile.
authors.forename: Francisco A
authors.initials: FA
authors.lastname: Cubillos
mesh_terms: D000483:Alleles; D001217:Aspartate-Ammonia Ligase / Q000235:genetics* / Q000378:metabolism; D001483:Base Sequence; D002678:Chimera; D003433:Crosses, Genetic; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D056726:Genetic Association Studies; D014644:Genetic Variation; D016681:Genome, Fungal; D040582:Inheritance Patterns; D009584:Nitrogen / Q000378:metabolism; D016366:Open Reading Frames; D011401:Promoter Regions, Genetic; D040641:Quantitative Trait Loci; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: C000613105:ASN1 protein, S cerevisiae; D004268:DNA-Binding Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C092661:UGA3 protein, S cerevisiae; D001217:Aspartate-Ammonia Ligase; D009584:Nitrogen