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Title: Genome-wide association across Saccharomyces cerevisiae strains reveals substantial variation in underlying gene requirements for toxin tolerance

Abstract

Cellulosic plant biomass is a promising sustainable resource for generating alternative biofuels and biochemicals with microbial factories. But a remaining bottleneck is engineering microbes that are tolerant of toxins generated during biomass processing, because mechanisms of toxin defense are only beginning to emerge. Here, we exploited natural diversity in 165 Saccharomyces cerevisiae strains isolated from diverse geographical and ecological niches, to identify mechanisms of hydrolysate-toxin tolerance. We performed genome-wide association (GWA) analysis to identify genetic variants underlying toxin tolerance, and gene knockouts and allele-swap experiments to validate the involvement of implicated genes. In the process of this work, we uncovered a surprising difference in genetic architecture depending on strain background: in all but one case, knockout of implicated genes had a significant effect on toxin tolerance in one strain, but no significant effect in another strain. In fact, whether or not the gene was involved in tolerance in each strain background had a bigger contribution to strain-specific variation than allelic differences. Our results suggest a major difference in the underlying network of causal genes in different strains, suggesting that mechanisms of hydrolysate tolerance are very dependent on the genetic background. These results could have significant implications for interpreting GWA resultsmore » and raise important considerations for engineering strategies for industrial strain improvement.« less

Authors:
ORCiD logo [1]; ORCiD logo [2]; ORCiD logo [2];  [3];  [4];  [2]; ORCiD logo [5];  [6]
  1. Univ. of Wisconsin, Madison, WI (United States). Great Lakes Bioenergy Research Center, and Microbiology Training Program
  2. Univ. of Wisconsin, Madison, WI (United States). Great Lakes Bioenergy Research Center
  3. Univ. of Wisconsin, Madison, WI (United States). Microbiology Training Program
  4. Univ. of Wisconsin, Madison, WI (United States). Lab. of Genetics
  5. Univ. of Wisconsin, Madison, WI (United States). Great Lakes Bioenergy Research Center, Lab. of Genetics
  6. Univ. of Rochester, NY (United States)
Publication Date:
Research Org.:
Univ. of Wisconsin, Madison, WI (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1499878
Grant/Contract Number:  
FC02-07ER64494
Resource Type:
Journal Article: Accepted Manuscript
Journal Name:
PLoS Genetics
Additional Journal Information:
Journal Volume: 14; Journal Issue: 2; Journal ID: ISSN 1553-7404
Publisher:
Public Library of Science
Country of Publication:
United States
Language:
English
Subject:
09 BIOMASS FUELS

Citation Formats

Sardi, Maria, Paithane, Vaishnavi, Place, Michael, Robinson, De Elegant, Hose, James, Wohlbach, Dana J., Gasch, Audrey P., and Fay, Justin C. Genome-wide association across Saccharomyces cerevisiae strains reveals substantial variation in underlying gene requirements for toxin tolerance. United States: N. p., 2018. Web. doi:10.1371/journal.pgen.1007217.
Sardi, Maria, Paithane, Vaishnavi, Place, Michael, Robinson, De Elegant, Hose, James, Wohlbach, Dana J., Gasch, Audrey P., & Fay, Justin C. Genome-wide association across Saccharomyces cerevisiae strains reveals substantial variation in underlying gene requirements for toxin tolerance. United States. doi:10.1371/journal.pgen.1007217.
Sardi, Maria, Paithane, Vaishnavi, Place, Michael, Robinson, De Elegant, Hose, James, Wohlbach, Dana J., Gasch, Audrey P., and Fay, Justin C. Fri . "Genome-wide association across Saccharomyces cerevisiae strains reveals substantial variation in underlying gene requirements for toxin tolerance". United States. doi:10.1371/journal.pgen.1007217. https://www.osti.gov/servlets/purl/1499878.
@article{osti_1499878,
title = {Genome-wide association across Saccharomyces cerevisiae strains reveals substantial variation in underlying gene requirements for toxin tolerance},
author = {Sardi, Maria and Paithane, Vaishnavi and Place, Michael and Robinson, De Elegant and Hose, James and Wohlbach, Dana J. and Gasch, Audrey P. and Fay, Justin C.},
abstractNote = {Cellulosic plant biomass is a promising sustainable resource for generating alternative biofuels and biochemicals with microbial factories. But a remaining bottleneck is engineering microbes that are tolerant of toxins generated during biomass processing, because mechanisms of toxin defense are only beginning to emerge. Here, we exploited natural diversity in 165 Saccharomyces cerevisiae strains isolated from diverse geographical and ecological niches, to identify mechanisms of hydrolysate-toxin tolerance. We performed genome-wide association (GWA) analysis to identify genetic variants underlying toxin tolerance, and gene knockouts and allele-swap experiments to validate the involvement of implicated genes. In the process of this work, we uncovered a surprising difference in genetic architecture depending on strain background: in all but one case, knockout of implicated genes had a significant effect on toxin tolerance in one strain, but no significant effect in another strain. In fact, whether or not the gene was involved in tolerance in each strain background had a bigger contribution to strain-specific variation than allelic differences. Our results suggest a major difference in the underlying network of causal genes in different strains, suggesting that mechanisms of hydrolysate tolerance are very dependent on the genetic background. These results could have significant implications for interpreting GWA results and raise important considerations for engineering strategies for industrial strain improvement.},
doi = {10.1371/journal.pgen.1007217},
journal = {PLoS Genetics},
issn = {1553-7404},
number = 2,
volume = 14,
place = {United States},
year = {2018},
month = {2}
}

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