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 »
- Authors:
-
[1];
[2];
[2];
[5];
- Univ. of Wisconsin, Madison, WI (United States). Great Lakes Bioenergy Research Center, and Microbiology Training Program
- Univ. of Wisconsin, Madison, WI (United States). Great Lakes Bioenergy Research Center
- Univ. of Wisconsin, Madison, WI (United States). Microbiology Training Program
- Univ. of Wisconsin, Madison, WI (United States). Lab. of Genetics
- Univ. of Wisconsin, Madison, WI (United States). Great Lakes Bioenergy Research Center, Lab. of Genetics
- 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:
- 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. https://doi.org/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. https://doi.org/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},
number = 2,
volume = 14,
place = {United States},
year = {Fri Feb 23 00:00:00 EST 2018},
month = {Fri Feb 23 00:00:00 EST 2018}
}
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