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

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...

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Bibliographic Details
Published in:PLoS genetics 2018-02, Vol.14 (2), p.e1007217-e1007217
Main Authors: Sardi, Maria, Paithane, Vaishnavi, Place, Michael, Robinson, De Elegant, Hose, James, Wohlbach, Dana J, Gasch, Audrey P
Format: Article
Language:English
Subjects:
09 BIOMASS FUELS
Alternative energy sources
Architectural engineering
Biodiesel fuels
Biofuels
Bioinformatics
Biology and Life Sciences
Biomass
Fermentation
Funding
Genes
Genetic analysis
Genetic aspects
Genetic diversity
Genetics
Genome-wide association studies
Genomes
Laboratories
Medicine and Health Sciences
Physiology
Research and Analysis Methods
Saccharomyces cerevisiae
Scholarships & fellowships
Toxins
Yeast
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Summary: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.
ISSN:1553-7404
1553-7390
1553-7404
DOI:10.1371/journal.pgen.1007217