GSE69115
Natural variation in non-coding regions underlying phenotypic diversity in budding yeast
Determining the different sources of heritable variation underlying quantitative traits in nature is currently at the forefront of genetic studies. To this end, molecular profiling studies in S. cerevisiae have shown that individual gene expression levels are subject to genetic control and this variation can mediate genetic differences on phenotype. Thus, determining how natural variation influences allele specific expression (ASE) and ultimately complex traits represents a useful tool to determine the mechanisms leading to yeast niche adaptation. Here, in order to test the hypothesis that allele-specific expression differences between isolates contributes to the phenotypic diversity in natural populations, we evaluated ASE levels in a grid of six F1 hybrids from the cross of four representative founder strains from major lineages. Genome-wide and across hybrids we quantified ASE for 3,320 genes. We found evidence for abundant genome-wide expression differences between alleles, with levels ranging between 27% up to 61% of the evaluated genes, depending on the cross. We observed that ASE can be explained by allele-specific differences in transcription factor binding to cis-regulatory regions and differences in strain-specific trans-activation can be detected by taking advantage of the shared trans environment of F1 hybrids. Furthermore, modules of genes under cis-regulatory variation with related function are enriched within the different genetic backgrounds, supporting the premise of intraspecies directional regulatory selection in yeast. Finally, we were able to identify two genes, GDB1 and ASN1 exhibiting high expression levels in the Wine/European strain and underlying phenotypic differences for oenological phenotypes due to polymorphisms within non-coding regions, providing direct evidence of the importance of regulatory variation in natural trait diversity. Overall design: ASE analysis in 6 F1 hybrids in triplicates