title: Cascading transcriptional effects of a naturally occurring frameshift mutation in Saccharomyces cerevisiae.
abstract: Gene-expression variation in natural populations is widespread, and its phenotypic effects can be acted upon by natural selection. Only a few naturally segregating genetic differences associated with expression variation have been identified at the molecular level. We have identified a single nucleotide insertion in a vineyard isolate of Saccharomyces cerevisiae that has cascading effects through the gene-expression network. This allele is responsible for about 45% (103/230) of the genes that show differential gene expression among the homozygous diploid progeny produced by a vineyard isolate. Using isogenic laboratory strains, we confirm that this allele causes dramatic differences in gene-expression levels of key genes involved in amino acid biosynthesis. The mutation is a frameshift mutation in a mononucleotide run of eight consecutive T's in the coding region of the gene SSY1, which encodes a key component of a plasma-membrane sensor of extracellular amino acids. The potentially high rate of replication slippage of this mononucleotide repeat, combined with its relatively mild effects on growth rate in heterozygous genotypes, is sufficient to account for the persistence of this phenotype at low frequencies in natural populations.
authors.affiliation: Department of Organismic and Evolutionary Biology, Harvard University, 16 Divinity Avenue, Cambridge, MA 02138, USA. kmbrown@fas.harvard.edu
authors.forename: Kyle M
authors.initials: KM
authors.lastname: Brown
authors.forename: Christian R
authors.initials: CR
authors.lastname: Landry
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Hartl
authors.forename: Duccio
authors.initials: D
authors.lastname: Cavalieri
mesh_terms: D000483:Alleles; D016368:Frameshift Mutation; D015966:Gene Expression Regulation, Fungal; D005787:Gene Frequency; D005816:Genetic Complementation Test; D005838:Genotype; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000254:growth & development; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics*; D017422:Sequence Analysis, DNA; D014158:Transcription, Genetic
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C120527:SSY1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins