High resolution QTL mapping of ethanol tolerance in Saccharomyces cerevisiae using an integrative genomics approach

Roni Haas 1 Guy Horev 2 Ehud Lipkin 3 Inbar Kesten 1 Keren Buhnik-Rosenblau 1 Morris Soller 3 Yechezkel Kashi 1
1Biotechnology and Food Engineering, Technion-Israel Institute of Technology, Haifa, Israel
2Bioinformatics Knowledge Unit, Technion-Israel Institute of Technology, Haifa, Israel
3Department of Genetics, The Hebrew University of Jerusalem, Jerusalem, Israel

Ethanol, produced by Saccharomyces cerevisiae fermentations, is the main biofuel used worldwide. The toxicity effect of ethanol on yeast, which inhibits fermentation and industrial productivity, calls for better understanding of the genetic basis of ethanol tolerance. However, until now genomic elements affecting ethanol tolerance have only been mapped at low resolution, hindering their identification. Here, we used an Advanced Intercross Line design, to perform high resolution mapping of QTLs affecting ethanol tolerance in yeast. Selective DNA Pooling and whole-genome sequencing were carried out in the F6 of a cross between two widely separated S. cerevisiae strains. Fifty-one and 96 QTL regions (QTLR) respectively affecting growth and survival under ethanol stress, were identified by applying a unique statistical pipeline based on LOESS smoothing to identify QTLs and Log drop to determine QTLR boundaries. We identified a larger number of QTLs than in any previous single mapping study in yeast, with a high resolution; in some cases, down to single genes. Some QTL overlap observed between the growth and survival traits, suggesting partially shared mechanisms. Finally, enrichment analysis highlighted biological processes important for ethanol tolerance in S. cerevisiae. The presented integrative genomics approach can be applied with any sexual model organism for high resolution mapping.