title: Genetic architecture of ethanol-responsive transcriptome variation in Saccharomyces cerevisiae strains.
abstract: Natural variation in gene expression is pervasive within and between species, and it likely explains a significant fraction of phenotypic variation between individuals. Phenotypic variation in acute systemic responses can also be leveraged to reveal physiological differences in how individuals perceive and respond to environmental perturbations. We previously found extensive variation in the transcriptomic response to acute ethanol exposure in two wild isolates and a common laboratory strain of Saccharomyces cerevisiae. Many expression differences persisted across several modules of coregulated genes, implicating trans-acting systemic differences in ethanol sensing and/or response. Here, we conducted expression QTL mapping of the ethanol response in two strain crosses to identify the genetic basis for these differences. To understand systemic differences, we focused on "hotspot" loci that affect many transcripts in trans. Candidate causal regulators contained within hotspots implicate upstream regulators as well as downstream effectors of the ethanol response. Overlap in hotspot targets revealed additive genetic effects of trans-acting loci as well as "epi-hotspots," in which epistatic interactions between two loci affected the same suites of downstream targets. One epi-hotspot implicated interactions between Mkt1p and proteins linked to translational regulation, prompting us to show that Mkt1p localizes to P bodies upon ethanol stress in a strain-specific manner. Our results provide a glimpse into the genetic architecture underlying natural variation in a stress response and present new details on how yeast respond to ethanol stress.
authors: Department of Biological Sciences, University of Arkansas, Fayetteville, Arkansas 72701 Laboratory of Genetics, University of Wisconsin, Madison, Wisconsin 53704 Great Lakes Bioenergy Research Center, University of Wisconsin, Madison, Wisconsin 53704.
authors: Jeffrey A
authors: JA
authors: Lewis
authors: Department of Biostatistics and Medical Informatics, University of Wisconsin, Madison, Wisconsin 53704.
authors: Aimee T
authors: AT
authors: Broman
authors: Laboratory of Genetics, University of Wisconsin, Madison, Wisconsin 53704.
authors: Jessica
authors: J
authors: Will
authors: Laboratory of Genetics, University of Wisconsin, Madison, Wisconsin 53704 Great Lakes Bioenergy Research Center, University of Wisconsin, Madison, Wisconsin 53704 agasch@wisc.edu.
authors: Audrey P
authors: AP
authors: Gasch
mesh_terms: D004843:Epistasis, Genetic; D000431:Ethanol / Q000378:metabolism / Q000494:pharmacology*; D014644:Genetic Variation; D016681:Genome, Fungal; D040641:Quantitative Trait Loci; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics; D059467:Transcriptome
chemical_list: C092218:MKT1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D000431:Ethanol
keywords: Saccharomyces cerevisiae; eQTL mapping; environmental stress; gene expression; natural variation