Biology subjects

Fay, J. C.

Publications and source records attributed to Fay, J. C..

22 records · Page 2Linked to original sources

bioRxiv2018

Genetic basis of variation in heat and ethanol tolerance in Saccharomyces cerevisiae

Saccharomyces cerevisiae has the capability of fermenting sugar to produce concentrations of ethanol that are toxic to most organisms. Other Saccharomyces species also have a strong fermentative capacity, but some are specialized to low temperatures, whereas S. cerevisiae is the most thermotolerant. Although S. cerevisiae has been extensively used to study the genetic basis of ethanol tolerance, much less is known about temperature dependent ethanol tolerance. In this study, we examined the genetic basis of ethanol tolerance at high temperature among strains of S. cerevisiae. We identified two amino acid polymorphisms in SEC24 that cause strong sensitivity to ethanol at high temperature and more limited sensitivity to temperature in the absence of ethanol. We also identified a single amino acid polymorphism in PSD1 that causes sensitivity to high temperature in a strain dependent fashion. The genes we identified provide further insight into genetic variation in ethanol and temperature tolerance and the interdependent nature of these two traits in S. cerevisiae.

genetics↗

bioRxiv2017

Comparative genomics approaches accurately predict deleterious variants in plants

Recent advances in genome resequencing have led to increased interest in prediction of the functional consequences of genetic variants. Variants at phylogenetically conserved sites are of particular interest, because they are more likely than variants at phylogenetically variable sites to have deleterious effects on fitness and contribute to phenotypic variation. Numerous comparative genomic approaches have been developed to predict deleterious variants, but the approaches are nearly always assessed based on their ability to identify known disease-causing mutations in humans. Determining the accuracy of deleterious variant predictions in nonhuman species is important to understanding evolution, domestication, and potentially to improving crop quality and yield. To examine our ability to predict deleterious variants in plants we generated a curated database of 2,910 Arabidopsis thaliana mutants with known phenotypes. We evaluated seven approaches and found that while all performed well, their relative ranking differed from prior benchmarks in humans. We conclude that deleterious mutations can be reliably predicted in A. thaliana and likely other plant species, but that the relative performance of various approaches does not necessarily translate from one species to another.

bioinformatics↗

bioRxiv2016

Understanding genetic changes underlying the molybdate resistance and the glutathione production in Saccharomyces cerevisiae wine strains using an evolution-based strategy

In this work we have investigated the genetic changes underlying the high glutathione (GSH) production showed by the evolved Saccharomyces cerevisiae strain UMCC 2581, selected in a molybdate-enriched environment after sexual recombination of the parental wine strain UMCC 855. To reach our goal, we first generated strains with the desired phenotype, and then we mapped changes underlying adaptation to molybdate by using a whole-genome sequencing. Moreover, we carried out the RNA-seq that allowed an accurate measurement of gene expression and an effective comparison between the transcriptional profiles of parental and evolved strains, in order to investigate the relationship between genotype and high GSH production phenotype.\n\nAmong all genes evaluated only two genes, MED2 and RIM15 both related to oxidative stress response, presented new mutations in the UMCC 2581 strain sequence and were potentially related to the evolved phenotype.\n\nRegarding the expression of high GSH production phenotype, it included over-expression of amino acids permeases and precursor biosynthetic enzymes rather than the two GSH metabolic enzymes, whereas GSH production and metabolism, transporter activity, vacuolar detoxification and oxidative stress response enzymes were probably added resulting in the molybdate resistance phenotype. This work provides an example of a combination of an evolution-based strategy to successful obtain yeast strain with desired phenotype and inverse engineering approach to genetic characterize the evolved strain. The obtained genetic information could be useful for further optimization of the evolved strains and for providing an even more rapid approach to identify new strains, with a high GSH production, through a marked-assisted selection strategy.

genomics↗

bioRxiv2016

Directional evolution in temperature-responsive gene expression in yeast

Gene regulation is a ubiquitous mechanism by which organisms respond to their environment. While organisms are often found to be adapted to the environments they experience, the role of gene regulation in environmental adaptation is not often known. In this study, we examine divergence in cis-regulatory effects between two Saccharomyces species, S. cerevisiae and S. uvarum, that have substantially diverged in their thermal growth profile. We measured allele specific expression (ASE) in the species hybrid at three temperatures, the highest of which is lethal to S. uvarum but not the hybrid or S. cerevisiae. We find that S. uvarum alleles can be expressed at the same level as S. cerevisiae alleles at high temperature and most cis-acting differences in gene expression are not dependent on temperature. While a small set of 136 genes show temperature-dependent ASE, we find no indication that signatures of directional cis-regulatory evolution are associated with temperature. Within promoter regions we find binding sites enriched upstream of temperature responsive genes, but only weak correlations between binding site and expression divergence. Our results indicate that temperature divergence between S. cerevisiae and S. uvarum has not caused widespread divergence in cis-regulatory activity, but point to a small subset of genes where the species alleles show differences in magnitude or opposite responses to temperature. The difficulty of explaining divergence in cis-regulatory sequences with models of transcription factor binding sites and nucleosome positioning highlights the importance of identifying mutations that underlie cis-regulatory divergence between species.

genomics↗