AbstractThe genetic basis of the phenotypic diversity of yeast is still poorly understood. Wine yeast strains have specific abilities to grow and ferment under stressful conditions compared with other strains, but the genetic basis underlying these traits is unknown. Understanding how sequence variation influences such phenotypes is a major challenge to address adaptation mechanisms of wine yeast. We aimed to identify the genetic basis of fermentation traits and gain insight into their relationships with variations in gene expression among yeast strains. We combined fermentation trait QTL mapping and expression profiling of fermenting cells in a segregating population from a cross between a wine yeast derivative and a laboratory strain. We report the identification of QTL for various fermentation traits (fermentation rates, nitrogen utilization, metabolites production) as well as expression QTL (eQTL). We found that many transcripts mapped to several eQTL hotspots and that two of them overlapped with QTL for fermentation traits. A QTL controlling the maximal fermentation rate and nitrogen utilization overlapping with an eQTL hotspot was dissected. We functionally demonstrated that an allele of the ABZ1 gene, localized in the hotspot and involved in p-aminobenzoate biosynthesis, controls the fermentation rate through modulation of nitrogen utilization. Our data suggest that the laboratory strain harbors a defective ABZ1 allele, which triggers strong metabolic and physiological alterations responsible for the generation of the eQTL hotspot. They also suggest that a number of gene expression differences result from some alleles that trigger major physiological disturbances.