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

PLoS Genetics
Maria SardiAudrey P Gasch

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 diff...Continue Reading

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Citations

Apr 13, 2018·Current Genetics·Maria Sardi, Audrey P Gasch
Jan 8, 2020·ELife·James HoseAudrey P Gasch
Oct 26, 2018·Biotechnology for Biofuels·Damien Biot-PelletierVincent J J Martin
Sep 24, 2020·G3 : Genes - Genomes - Genetics·Hayley R StonemanChris Todd Hittinger
Nov 7, 2020·Frontiers in Bioengineering and Biotechnology·Eugene Fletcher, Kristin Baetz
Jun 8, 2021·Applied Microbiology and Biotechnology·B A BrandtR Den Haan
Sep 27, 2020·BMC Evolutionary Biology·Tuc H M NguyenHeather L Fiumera

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Datasets Mentioned

BETA
PRJEB24747

Methods Mentioned

BETA
PCA
protein folding
gene-knockout
gene knockouts
dissection
PCRs
PCR

Software Mentioned

mem
R package Adegenet
VCFtools
GATK Unified Genotyper
bwa
SNPEff
GAPIT
GATK
SynH

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