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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Genet. | doi: 10.3389/fgene.2019.00998

Mapping Ethanol Tolerance in Budding Yeast Reveals High Genetic Variation in a Wild Isolate

Roni Haas1,  Guy Horev2,  Ehud Lipkin3, Inbar Kesten1, Maya Portnoy1, Keren Buhnik-Rosenblau1, Morris Soller3 and  Yechezkel‏ Kashi1*
  • 1Technion Israel Institute of Technology, Israel
  • 2Technion Bioinformatics Knowledge Unit, Faculty of Biology, Technion Israel Institute of Technology, Israel
  • 3Hebrew University of Jerusalem, Israel

Ethanol tolerance, a polygenic trait of the yeast Saccharomyces cerevisiae, is the primary factor determining industrial bioethanol productivity. Until now, genomic elements affecting ethanol tolerance have been mapped only at low resolution, hindering their identification. Here, we explore the genetic architecture of ethanol tolerance, in the F6 generation of an Advanced Intercross Line (AIL) mapping population between two phylogenetically distinct, but phenotypically similar, S. cerevisiae strains (a common laboratory strain and a wild strain isolated from nature). Under ethanol stress, 51 QTLs affecting growth and 96 QTLs affecting survival, most of them novel, were identified, with high resolution, in some cases to single genes, using a High-Resolution Mapping Package of methodologies that provided high power and high resolution. We confirmed our results experimentally by showing the effects of the novel mapped genes: MOG1, MGS1 and YJR154W. The mapped QTLs explained 34% of phenotypic variation for growth and 72% for survival. High statistical power provided by our analysis allowed detection of many loci with small, but mappable effects, uncovering a novel "quasi-infinitesimal" genetic architecture. These results are striking demonstration of tremendous amounts of hidden genetic variation exposed in crosses between phylogenetically separated strains with similar phenotypes; as opposed to the more common design where strains with distinct phenotypes are crossed. Our findings suggest that ethanol tolerance is under natural evolutionary fitness-selection for an optimum phenotype that would tend to eliminate alleles of large effect. The study provides a platform for development of superior ethanol-tolerant strains using genome editing or selection.

Keywords: Allele effect, causative genes, Genetic architecture of complex trait, Saccharomyces cerevisiae, QTL mapping

Received: 02 May 2019; Accepted: 18 Sep 2019.

Copyright: © 2019 Haas, Horev, Lipkin, Kesten, Portnoy, Buhnik-Rosenblau, Soller and Kashi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Yechezkel‏ Kashi, Technion Israel Institute of Technology, Haifa, 3200003, Haifa, Israel, kashi@technion.ac.il