Biology subjects

Wrobel, R. L.

Publications and source records attributed to Wrobel, R. L..

4 recordsLinked to original sources

bioRxiv2024

Machine learning uncovers gene families impacting oxidative stress resistance across yeasts

Reactive oxygen species (ROS) are highly reactive molecules encountered by yeasts during routine metabolism and during interactions with other organisms, including host infection. Here, we characterized the variation in resistance to ROS across the ancient yeast subphylum Saccharomycotina and used machine learning (ML) to identify gene families whose sizes were predictive of ROS resistance. The most predictive features were enriched in gene families related to cell wall organization and included two reductase gene families. We estimated the quantitative contributions of features to each species classification to guide experimental validation and showed that overexpression of the old yellow enzyme (OYE) reductase increased ROS resistance in Kluyveromyces lactis, while Saccharomyces cerevisiae mutants lacking multiple mannosyltransferase-encoding genes were hypersensitive to ROS. Altogether, this work provides a framework for how ML can uncover genetic mechanisms underlying trait variation across diverse species and inform trait manipulation for clinical and biotechnological applications.

microbiology↗

bioRxiv2022

Macroevolutionary diversity of traits and genomes in the model yeast genus Saccharomyces

Species is the fundamental unit to quantify biodiversity. In recent years, the model yeast Saccharomyces cerevisiae has seen an increased number of studies related to its geographical distribution, population structure, and phenotypic diversity. However, seven additional species from the same genus have been less thoroughly studied, which has limited our understanding of the macroevolutionary leading to the diversification of this genus over the last 20 million years. Here, we report the geographies, hosts, substrates, and phylogenetic relationships for approximately 1,800 Saccharomyces strains, covering the complete genus with unprecedented breadth and depth. We generated and analyzed complete genome sequences of 163 strains and phenotyped 128 phylogenetically diverse strains. This dataset provides insights about genetic and phenotypic diversity within and between species and populations, quantifies reticulation and incomplete lineage sorting, and demonstrates how gene flow and selection have affected traits, such as galactose metabolism. These findings elevate the genus Saccharomyces as a model to understand biodiversity and evolution in microbial eukaryotes.

evolutionary biology↗

bioRxiv2020

CRISpy-pop: a web tool for designing CRISPR/Cas9-driven genetic modifications in diverse populations

CRISPR/Cas9 is a powerful tool for editing genomes, but design decisions are generally made with respect to a single reference genome. With population genomic data becoming available for an increasing number of model organisms, researchers are interested in manipulating multiple strains and lines. CRISpy-pop is a web application that generates and filters guide RNA sequences for CRISPR/Cas9 genome editing for diverse yeast and bacterial strains. The current implementation designs and predicts the activity of guide RNAs against more than 1000 Saccharomyces cerevisiae genomes, including 167 strains frequently used in bioenergy research. Zymomonas mobilis, an increasingly popular bacterial bioenergy research model, is also supported. CRISpy-pop is available as a web application (https://CRISpy-pop.glbrc.org/) with an intuitive graphical user interface. CRISpy-pop also cross-references the human genome to allow users to avoid the selection of sgRNAs with potential biosafety concerns. Additionally, CRISpy-pop predicts the strain coverage of each guide RNA within the supported strain sets, which aids in functional population genetic studies. Finally, we validate how CRISpy-pop can accurately predict the activity of guide RNAs across strains using population genomic data.

genetics↗

bioRxiv2019

Allododecaploid yeasts: synthetic hybrids of six species

Allopolyploidy generates diversity by increasing the number of copies and sources of chromosomes. Many of the best-known evolutionary radiations, crops, and industrial organisms are ancient or recent allopolyploids. Allopolyploidy promotes differentiation and facilitates adaptation to new environments, but the tools to test its limits are lacking. Here we develop an iterative method to combine the genomes of multiple budding yeast species, generating Saccharomyces allopolyploids of an unprecedented scale. Chromosomal instability and cell size increased dramatically as additional copies of the genome were added, but we were able to construct synthetic hybrids of up to six species. The six-species hybrids initially grew slowly, but they rapidly adapted when selection to a novel environment was applied, even as they retained traits from multiple species. These new synthetic yeast hybrids have potential applications for the study of polyploidy, genome stability, chromosome segregation, cancer, and bioenergy. One sentence summaryWe constructed six-species synthetic hybrids and showed that they were chromosomally unstable but able to adapt rapidly.

genetics↗