AGAPE (Automated Genome Analysis PipelinE) for Pan-Genome Analysis of Saccharomyces cerevisiae

Song, Giltae; Dickins, Benjamin; Demeter, János; Engel, Stacia R.; Dunn, Barbara K.; Cherry, J. Michael

doi:10.1371/journal.pone.0120671

Cited by 69 publications

(62 citation statements)

References 60 publications

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“…Although comparable to the previously published BY4741 draft genome 27 , the quality metrics of all assemblies varied markedly from the S288C reference in number of contigs and N50 values. Cost is a major barrier to using WGS for sample verification, and cost directly relates to coverage.…”

Section: Assembling a Genome For Verificationsupporting

confidence: 67%

Challenges and opportunities for strain verification by whole-genome sequencing

Gallegos

Adames

Häyrynen³

et al. 2019

Preprint

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Laboratory strains, cell lines, and other genetic materials change hands frequently in the life sciences. Despite evidence that such materials are subject to mix-ups, contamination, and accumulation of secondary mutations, verification of strains and samples is not an established part of many experimental workflows. With the plummeting cost of next generation technologies, it is conceivable that whole genome sequencing (WGS) could be applied to routine strain and sample verification in the future. To demonstrate the need for strain validation by WGS, we sequenced haploid yeast segregants derived from a popular commercial mutant collection and identified several unexpected mutations. We determined that available bioinformatics tools may be ill-suited for verification and highlight the importance of finishing reference genomes for commonly-used laboratory strains.

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Section: Assembling a Genome For Verificationsupporting

confidence: 67%

Challenges and opportunities for strain verification by whole-genome sequencing

Gallegos

Adames

Häyrynen³

et al. 2019

Preprint

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“…While BY4741 yke4 was MCHM sensitivity, deletion in S288c and YJM789 had no effect. There are hundreds of genetic differences between BY4741 and S288c and thousands in YJM789 (44,45). Other yeast strains have the H5Q polymorphism and a subset of those also have the F86L polymorphism.…”

Section: Discussionmentioning

confidence: 99%

MCHM acts as a hydrotrope, altering the balance of metals in yeast

Pupo

Ayers

Sherman

et al. 2019

Preprint

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While drugs and other industrial chemicals are routinely studied to assess risks, many widely-used chemicals have not been thoroughly evaluated. One such chemical, 4-methylcyclohexane methanol (MCHM), is an industrial coal-cleaning chemical that contaminated the drinking-water supply in Charleston, WV, USA in 2014. While a wide range of ailments was reported following the spill, little is known about the molecular effects of MCHM exposure. We used the yeast model to explore the impacts of MCHM on cellular function. Exposure to MCHM dramatically altered the yeast transcriptome and the balance of metals in yeast. Underlying genetic variation in the response to MCHM and transcriptomics and mutant analysis uncovered the role of the metal transporters, Arn2 and Yke4, to MCHM response.Expression of Arn2, involved in iron uptake, was lower in MCHM-tolerant yeast and loss of Arn2 further increased MCHM tolerance. Genetic variation within Yke4, an ER zinc transporter, also mediated response to MCHM and loss of Yke4 decreased MCHM tolerance. The addition of zinc to MCHMsensitive yeast rescued growth inhibition. In vitro assays demonstrated that MCHM acted as a hydrotrope and prevented protein-interactions, while zinc-induced the aggregation of proteins. We hypothesized that MCHM altered the structures of extracellular domains of proteins, and the addition of zinc stabilized the structure to maintain metal homeostasis in yeast exposed to MCHM. BackgroundThe potential for significant human exposure to toxic substances is increasing as thousands of chemicals in routine use have had little safety testing (1-3). 4-Methylcyclohexanemethanol (MCHM) is alicyclic primary alcohol used as a cleaning agent in the coal industry. Although health and safety information for this compound is limited, its widespread use in the coal-producing regions of the United States represents a potential hazard to humans and ecosystems. In January 2014, a large quantity of MCHM was spilled into the Elk River in West Virginia, USA and contaminated the drinking water supply of 300,000 people, exposing them to unknown health risks (4). People exposed to MCHM through the contaminated drinking water reported a variety of significant ill effects (5).MCHM is not easily degraded biologically because of its low reactivity (6). In contrast to other well-studied hydrocarbons, such as cyclohexane and benzene, the effects of MCHM on metabolism are under studied (7). Yeast lines exposed to MCHM exhibited increased expression of proteins associated with the membrane, cell wall, and cell structure functions, while MCHM metabolites mainly induced proteins related to antioxidant activity and oxidoreductase activity (3). With human A549 cells, MCHM mainly induced DNA damage-related biomarkers, which indicates that MCHM is related to genotoxicity due to its DNA damage effect on human cells (3).Yeast provide an ideal model system to understand the interplay between metabolic pathways involved in the transport, toxicity, and detoxification of MCHM. Further, the use of yeast...

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“…S5). In the S. cerevisiae population, almost all sequenced PMR1 alleles have leucine-548, with phenylalanine-548 found only in BY and other laboratory yeast strains (Liti et al 2009;Song et al 2015) whose PMR1 alleles are likely directly related to BY (Schacherer et al 2009). This region of BY Chr 7 is inherited from EM93, a diploid yeast strain isolated from a fig in California in 1938 (Mortimer and Johnston 1986).…”

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confidence: 99%

CRISPR-directed mitotic recombination enables genetic mapping without crosses

Sadhu

Bloom

Day

et al. 2016

Preprint

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Linkage and association studies have mapped thousands of genomic regions that contribute to phenotypic variation, but narrowing these regions to the underlying causal genes and variants has proven much more challenging. Resolution of genetic mapping is limited by the recombination rate. We developed a method that uses CRISPR to build mapping panels with targeted recombination events. We tested the method by generating a panel with recombination events spaced along a yeast chromosome arm, mapping trait variation, and then targeting a high density of recombination events to the region of interest. Using this approach, we fine-mapped manganese sensitivity to a single polymorphism in the transporter Pmr1. Targeting recombination events to regions of interest allows us to rapidly and systematically identify causal variants underlying trait differences.. CC-BY-NC-ND 4.0 International license peer-reviewed) is the author/funder. It is made available under aThe copyright holder for this preprint (which was not . http://dx.doi.org/10.1101/040428 doi: bioRxiv preprint first posted online Identification of DNA sequence differences that underlie trait variation is a central goal of modern genetic research. The primary tools for connecting genotype and phenotype are linkage and association studies. In these studies, co-inheritance of genetic markers with the trait of interest in large panels of individuals is used to localize variants that influence the trait to specific regions of the genome. The localization relies on meiotic recombination events that break up linkage between markers on a chromosome. Therefore, the spatial resolution of genetic mapping is limited by the recombination rate.In practice, the recombination rate in most settings is too low to resolve mapped regions to individual genes, much less to specific variants within genes. Increasing mapping resolution requires construction of ever-larger panels of individuals and/or additional generations of recombination, and these approaches are laborious to the point of often being impractical. As a consequence, the genes and variants underlying trait variation remain unidentified for the vast majority of regions implicated by linkage or association mapping.To address this problem, we have devised a new method for genetic mapping that precisely targets recombination events to regions of interest. The method uses recombination events that occur during mitosis rather than meiosis. Rare mitotic recombination events occur naturally when a chromosomal double strand break (DSB) is repaired by homologous recombination (HR) that leads to the formation of a recombined chromosome (Yin and Petes 2013). In a heterozygous individual, cell division can then generate daughter cells with a new genotype that is completely homozygous from the . CC-BY-NC-ND 4.0 International license peer-reviewed) is the author/funder. It is made available under a The copyright holder for this preprint (which was not . http://dx.doi.org/10.1101/040428 doi: bioRxiv preprint first posted onli...

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AGAPE (Automated Genome Analysis PipelinE) for Pan-Genome Analysis of Saccharomyces cerevisiae

Cited by 69 publications

References 60 publications

Challenges and opportunities for strain verification by whole-genome sequencing

Challenges and opportunities for strain verification by whole-genome sequencing

MCHM acts as a hydrotrope, altering the balance of metals in yeast

CRISPR-directed mitotic recombination enables genetic mapping without crosses

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