985 research outputs found
Genetic variation and expression changes associated with molybdate resistance from a glutathione producing wine strain of Saccharomyces cerevisiae
No full textGlutathione (GSH) production during wine fermentation is a desirable trait as it can limit must and wine oxidation and protect various aromatic compounds. UMCC 2581 is a Saccharomyces cerevisiae wine strain with enhanced GSH content at the end of wine fermentation. This strain was previously derived by selection for molybdate resistance following a sexual cycle of UMCC 855 using an evolution-based strategy. In this study, we examined genetic and gene expression changes associated with the derivation of UMCC 2581. For genetic analysis we sporulated the diploid UMCC 855 parental strain and found four phenotype classes of segregants related to molybdate resistance, demonstrating the presence of segregating variation from the parental strain. Using bulk segregant analysis we mapped molybdate traits to two loci. By sequencing both the parental and evolved strain genomes we identified candidate mutations within the two regions as well as an extra copy of chromosome 1 in UMCC 2581. Combining the mapped loci with gene expression profiles of the evolved and parental strains we identified a number of candidate genes with genetic and/or gene expression changes that could underlie molybdate resistance and increased GSH levels. Our results provide insight into the genetic basis of GSH production relevant to winemaking and highlight the value of enhancing wine strains using existing variation present in wine strains
A multi-phase approach to select new wine yeast strains with enhanced fermentative fitness and glutathione production
No full textThe genetic improvement of winemaking yeasts is a virtually infinite process, as the design of new strains must always cope with varied and ever-evolving production contexts. Good wine yeasts must feature both good primary traits, which are related to the overall fermentative fitness of the strain, and secondary traits, which provide accessory features augmenting its technological value. In this context, the superiority of “blind,” genetic improvement techniques, as those based on the direct selection of the desired phenotype without prior knowledge of the genotype, was widely proven. Blind techniques such as adaptive evolution strategies were implemented for the enhancement of many traits of interest in the winemaking field. However, these strategies usually focus on single traits: this possibly leads to genetic tradeoff phenomena, where the selection of enhanced secondary traits might lead to sub-optimal primary fermentation traits. To circumvent this phenomenon, we applied a multi-step and strongly directed genetic improvement strategy aimed at combining a strong fermentative aptitude (primary trait) with an enhanced production of glutathione (secondary trait). We exploited the random genetic recombination associated to a library of 69 monosporic clones of strain UMCC 855 (Saccharomyces cerevisiae) to search for new candidates possessing both traits. This was achieved by consecutively applying three directional selective criteria: molybdate resistance (1), fermentative aptitude (2), and glutathione production (3). The strategy brought to the selection of strain 21T2-D58, which produces a high concentration of glutathione, comparable to that of other glutathione high-producers, still with a much greater fermentative aptitude
Supplemental Material for Riles and Fay, 2018
No full textData availability statement: All strains and constructs
are available upon request to the corresponding author. Supplemental Table 1: Strains used in this study. Supplemental
Table 2: Recombinant strain barcode indices, sequencing and phenotypes used for
QTL mapping. Supplemental Table 3: Primers used in this study. Supplemental
Table 4: Summary of candidate genes tested for two QTL regions. Supplemental
Table 5: Genes tested for complementation using a MoBY and/or a hemizygosity
test. Supplemental Table 6: Colony size measurements using ImageJ for HN6 X KO
Hemizygotes on Chromosome 14. Supplementary Figure 1: Ethanol and heat
sensitivity of control strains. Supplementary Figure 2: Logarithm of the odds
ratio (LOD) of a quantitative trait locus for heat and ethanol tolerance at
high temperature across the genome. Supplementary Figure 3: Protein alignment
of HN6, Oak and S288c for SEC24 and PSD1. Supplementary Figure 4: Phenotypes of resistant wild yeast
strains, Oak, Wine and S288c, containing high copy Oak allele plasmids grown at
40o. Data File S1. Genotypes and phenotypes of recombinant strains
used for QTL mapping. The raw data used to call genotypes for QTL mapping has
been deposited into NCBI's SRA under BioProject: PRJNA480857.</p
Comparative genomics approaches accurately predict deleterious variants in plants
No full textThe genes and mutations information in this table were downloaded from UniProt/Swiss-Prot database (http://www.uniprot.org/) and http://www.arabidopsis.org. Single nucleotide polymorphisms (SNPs) without any known phenotype were obtained from a set of 80 sequenced A. thaliana strains (Ensembl, version 81, “Cao_SNPs”, Cao, et al., 2011). We used six approaches: LRT, PolyPhen2, SIFT 4G, Provean, MAPP, Gerp++ to predict deleterious varaints. The details can be avaible in Kono, et al., 2017 (http://www.biorxiv.org/content/early/2017/02/27/112318)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 they are nearly always judged 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, the single best-performing approach was a likelihood ratio test applied to homologs identified in 42 plant genomes. Although the approaches did not always agree, we found only slight differences in performance when comparing mutations with gross versus biochemical phenotypes, duplicated versus single copy genes, and when using a single approach versus ensemble predictions. 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 can depend on the organism to which they are applied.US National Science Foundation Plant Genome Program grant (DBI-1339393 to JCF and PLM)US Department of Agriculture Biotechnology Risk Assessment Research Grants Program (BRAG) (USDA BRAG 2015-06504 to PLM)University of Minnesota Doctoral Dissertation Fellowship (to TJYK)Kono, Thomas John Y; Lei, Li; Shih, Ching-Hua; Hoffman, Paul J; Morrell, Peter L; Fay, Justin C. (2018). Comparative genomics approaches accurately predict deleterious variants in plants. Retrieved from the University Digital Conservancy, https://doi.org/10.13020/D6N69S
Variants from "The role of deleterious substitutions in crop genomes"
No full textThere are two gzipped VCF (variant call format) files with variant calls for barley and soybean. A total of 652,797 SNPs were identified in the barley lines, which consisted of 13 cultivars and 2 wild accessions. For soybean, 7 cultivars and 1 wild accession were used, and 586,102 SNPs were called. Whether a variant is deleterious or not was determined using SIFT (http://sift.jcvi.org/), PolyPhen2 (http://genetics.bwh.harvard.edu/pph2/), and a likelihood ratio test of sequence conservation. Raw reads are available through the SRA accession numbers in Table S1 of Kono et al. 2016. The code used for this research, BAD_Mutations, is open source and freely available at https://github.com/MorrellLAB/BAD_Mutations.SNP calls in protein coding regions were obtained from 15 barley and 8 soybean lines. Non synonymous SNPs were predicted to be deleterious or not using three approaches.USDA NIFA National Needs Fellowship (Appropriation No. 5430-21000-006-00D)MnDrive 2014 Food Security FellowshipMinnesota Agricultural Experiment Station Variety Development fundUnited Soybean BoardU.S. NSF Plant Genome Program (BDI-1339393)Kono, Thomas J Y; Fu, Fengli; Mohammadi, Mohsen; Hoffman, Paul J; Liu, Chaochih; Stupar, Robert M; Smith, Kevin P; Tiffin, Peter; Fay, Justin C; Morrell, Peter L. (2016). Variants from "The role of deleterious substitutions in crop genomes". Retrieved from the University Digital Conservancy, http://doi.org/10.13020/D65C7D
Long-term inhibition of ODC1 in APP/PS1 mice rescues amyloid pathology and switches astrocytes from a reactive to active state
No full textAlzheimer’s disease (AD) is characterized by the loss of memory due to aggregation of misphosphorylated tau and amyloid beta (Aβ) plaques in the brain, elevated release of inhibitory neurotransmitter gamma-aminobutyric acid (GABA) and reactive oxygen species from astrocytes, and subsequent neurodegeneration. Recently, it was found that enzyme Ornithine Decarboxylase 1 (ODC1) acts as a bridge between the astrocytic urea cycle and the putrescine-to-GABA conversion pathway in the brain of AD mouse models as well as human patients. In this study, we show that the long-term knockdown of astrocytic Odc1 in APP/PS1 animals was sufficient to completely clear Aβ plaques in the hippocampus while simultaneously switching the astrocytes from a detrimental reactive state to a regenerative active state, characterized by proBDNF expression. Our experiments also reveal an effect of astrocytic ODC1 inhibition on the expression of genes involved in synapse pruning and organization, histone modification, apoptotic signaling and protein processing. These genes are previously known to be associated with astrocytic activation and together create a neuroregeneration-supportive environment in the brain. By inhibiting ODC1 for a long period of 3 months in AD mice, we demonstrate that the beneficial amyloid-clearing process of astrocytes can be completely segregated from the systemically harmful astrocytic response to insult. Our study reports an almost complete clearance of Aβ plaques by controlling an endogenous degradation process, which also modifies the astrocytic state to create a regeneration-supportive environment in the brain. These findings present the potential of modulating astrocytic clearance of Aβ as a powerful therapeutic strategy against AD. © 2024, The Author(s).11Ysciescopu
Comment on “Exploring Groundwater Recoverability in Texas: Maximum Economically Recoverable Storage,” published in the Texas Water Journal (2020) 11(1):152-171, by Justin C. Thompson, Charles W. Kreitler, and Michael H. Young
No full textEditor-in-Chief\u27s Note: The Texas Water Journal accepted a request by Robert E. Mace, Executive Director and Chief Water Policy Officer at The Meadows Center for Water and the Environment, to share his thoughts on the article, Exploring Groundwater Recoverability in Texas: Maximum Economically Recoverable Storage,” published in the Texas Water Journal (2020) 11(1):152-171, by Justin C. Thompson, Charles W. Kreitler, and Michael H. Young. The opinion expressed in this commentary is the opinion of the individual author and not the opinion of the Texas Water Journal or the Texas Water Resources Institute
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Joint effects of genes underlying a temperature specialization tradeoff in yeast
No full textA central goal of evolutionary genetics is to understand, at the molecular level, how organisms adapt to their environments. For a given trait, the answer often involves the acquisition of variants at unlinked sites across the genome. Genomic methods have achieved landmark successes in pinpointing adaptive loci. To figure out how a suite of adaptive alleles work together, and to what extent they can reconstitute the phenotype of interest, requires their transfer into an exogenous background. We studied the joint effect of adaptive, gain-of-function thermotolerance alleles at eight unlinked genes from Saccharomyces cerevisiae, when introduced into a thermosensitive sister species, S. paradoxus. Although the loci damped each other's beneficial impact (that is, they were subject to negative epistasis), most boosted high-temperature growth alone and in combination, and none was deleterious. The complete set of eight genes was sufficient to confer ~15% of the S. cerevisiae phenotype in the S. paradoxus background. The same loci also contributed to a heretofore unknown advantage in cold growth by S. paradoxus. Together, our data establish temperature resistance in yeasts as a model case of a genetically complex evolutionary tradeoff, which can be partly reconstituted from the sequential assembly of unlinked underlying loci.Funding provided by: National Institutes of HealthCrossref Funder Registry ID: http://dx.doi.org/10.13039/100000002Award Number: R01 GM120430Funding provided by: National Science FoundationCrossref Funder Registry ID: http://dx.doi.org/10.13039/100000001Award Number: GRFP DGE 175281
Incomplete dominance of deleterious alleles contributes substantially to trait variation and heterosis in maize.
No full textDeleterious alleles have long been proposed to play an important role in patterning phenotypic variation and are central to commonly held ideas explaining the hybrid vigor observed in the offspring of a cross between two inbred parents. We test these ideas using evolutionary measures of sequence conservation to ask whether incorporating information about putatively deleterious alleles can inform genomic selection (GS) models and improve phenotypic prediction. We measured a number of agronomic traits in both the inbred parents and hybrids of an elite maize partial diallel population and re-sequenced the parents of the population. Inbred elite maize lines vary for more than 350,000 putatively deleterious sites, but show a lower burden of such sites than a comparable set of traditional landraces. Our modeling reveals widespread evidence for incomplete dominance at these loci, and supports theoretical models that more damaging variants are usually more recessive. We identify haplotype blocks using an identity-by-decent (IBD) analysis and perform genomic prediction analyses in which we weigh blocks on the basis of complementation for segregating putatively deleterious variants. Cross-validation results show that incorporating sequence conservation in genomic selection improves prediction accuracy for grain yield and other fitness-related traits as well as heterosis for those traits. Our results provide empirical support for an important role for incomplete dominance of deleterious alleles in explaining heterosis and demonstrate the utility of incorporating functional annotation in phenotypic prediction and plant breeding
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