A5075555945- Fungal and yeast genetics research
- Bioinformatics and Genomic Networks
- Evolution and Genetic Dynamics
- RNA and protein synthesis mechanisms
- Genomics and Phylogenetic Studies
- Fermentation and Sensory Analysis
- CRISPR and Genetic Engineering
- Microbial Metabolic Engineering and Bioproduction
- Antifungal resistance and susceptibility
- Pneumocystis jirovecii pneumonia detection and treatment
- Peptidase Inhibition and Analysis
- Biofuel production and bioconversion
- Machine Learning in Bioinformatics
- Biotin and Related Studies
- Antibiotic Resistance in Bacteria
- Protist diversity and phylogeny
- DNA Repair Mechanisms
- HIV/AIDS drug development and treatment
- Protein Kinase Regulation and GTPase Signaling
- RNA Research and Splicing
- Tuberculosis Research and Epidemiology
- Microtubule and mitosis dynamics
- Protein Structure and Dynamics
- Studies on Chitinases and Chitosanases
- Enzyme Production and Characterization
Université Laval
2014-2024
PROTEO
2015-2024
Université du Québec à Montréal
2023-2024
Département d'Informatique
2022-2023
Robustness of protein networks It is thought that gene duplication helps cells maintain genetic robustness, but this seems not to be the whole story. Diss et al. investigated fate protein-protein interactions among duplicated genes in yeast. Some interacting duplicates evolved mutual dependence, resulting a more fragile system. This finding us understand evolutionary trajectories duplications and how seemingly redundant can increase complexity interaction networks. Science , issue p. 630
Recent functional, proteomic and ribosome profiling studies in eukaryotes have concurrently demonstrated the translation of alternative open-reading frames (altORFs) addition to annotated protein coding sequences (CDSs). We show that a large number small proteins could fact be coded by these altORFs. The putative translated from altORFs orthologs many species contain functional domains. Evolutionary analyses indicate often more extreme conservation patterns than their CDSs. Thousands are...
Abstract Since deleterious mutations may be rescued by secondary during evolution, compensatory evolution could identify genetic solutions leading to therapeutic targets. Here, we tested this hypothesis and examined whether these would universal or need adapted one's environmental makeups. We performed experimental evolutionary rescue in a yeast disease model for the Wiskott–Aldrich syndrome two backgrounds carbon sources. found that multiple aspects of outcome depend on genotype,...
Significance Many studies have focused on the mechanisms of long-term retention gene duplicates, such as gain functions or reciprocal losses. However, changes are more likely to occur if duplicates maintained for a long period. This time span will be short duplication is immediately deleterious. We measured distribution fitness effects 899 genes in budding yeast. find that deleterious than beneficial. contrary previous models, general, does not affect by altering organization protein...
Abstract Critical mitochondrial functions, including cellular respiration, rely on frequently interacting components expressed from both the and nuclear genomes. The fitness of eukaryotic organisms depends a tight collaboration between In face an elevated rate evolution in mtDNA, current models predict that maintenance mitonuclear compatibility relies compensatory genome. Mitonuclear interactions would therefore exert influence evolutionary trajectories. One prediction this model is same...
The evolution of protein-coding genes proceeds as mutations act on two main dimensions: regulation transcription level and the coding sequence. extent impact connection between these dimensions are largely unknown because they have generally been studied independently. By measuring fitness effects all possible a protein complex at various levels promoter activity, we show that activity optimal for wild-type masks both deleterious beneficial mutations. Mutations low but masked slightly...
Cellular processes and homeostasis control in eukaryotic cells is achieved by the action of regulatory proteins such as protein kinase A (PKA). Although outbound signals from PKA directed to metabolism, growth, aging have been well charted, what regulates this conserved regulator remains be systematically identified understand how it coordinates biological processes. Using a yeast reporter assay, we genes that influence activity measuring protein-protein interactions between two catalytic...
Gene duplication is an important evolutionary mechanism that can result in functional divergence paralogs due to neo-functionalization or sub-functionalization. Consistent with after gene duplication, recent studies have shown accelerated evolution retained paralogs. However, little known general about the impact of this on molecular functions For example, do new typically involve changes enzymatic activities, protein regulation? Here we study posttranslational regulation by examining...
Little is known about the rate of emergence de novo genes, what their initial properties are, and how they spread in populations. We examined wild yeast populations ( Saccharomyces paradoxus ) to characterize diversity turnover intergenic ORFs over short evolutionary timescales. find that hundreds show translation signatures similar canonical we experimentally confirmed many these laboratory conditions using a reporter assay. Compared with have lower efficiency, which could imply lack...
Cells contain many important protein complexes involved in performing and regulating structural, metabolic, signaling functions. One major challenge cell biology is to elucidate the organization mechanisms of robustness these vivo. We developed a systematic approach study structural dependencies within living cells by deleting subunits measuring pairwise interactions among other components. used our methodology perturb two conserved eukaryotic complexes: retromer nuclear pore complex. Our...
Gene duplication is a driver of the evolution new functions. The genes encoding homomeric proteins leads to formation homomers and heteromers paralogs, creating complexes after single event. loss these may be required for two paralogs evolve independent Using yeast as model, we find that heteromerization frequent among duplicated correlates with functional similarity between paralogs. in silico evolution, show sharing binding interfaces, mutations one paralog can have structural pleiotropic...
Pneumocystis jirovecii is a fungal pathogen that causes pneumocystis pneumonia, disease mainly affects immunocompromised individuals. This fungus has historically been hard to study because of our inability grow it in vitro . One the main drug targets P its dihydrofolate reductase (PjDHFR). Here, by using functional complementation baker’s yeast ortholog, we show PjDHFR can be inhibited antifolate methotrexate dose-dependent manner. Using deep mutational scanning PjDHFR, identify mutations...
Despite the tremendous efforts devoted to identification of genetic incompatibilities underlying hybrid sterility and inviability, little is known about effect inter-species hybridization at protein interactome level. Here, we develop a screening platform for comparison protein-protein interactions (PPIs) among closely related species their hybrids. We examine in vivo architecture complexes two yeast (Saccharomyces cerevisiae Saccharomyces kudriavzevii) that diverged 5-20 million years ago...
Recent developments in DNA synthesis and sequencing have allowed the construction of comprehensive gene variant libraries their functional analysis. Achieving high-replication thorough mutation characterization remains technically financially challenging for long genes. Here, we developed an efficient, affordable scalable library approach that relies on low-cost standard cloning technologies, which will increase accessibility to systematic mutational studies help advance field protein science.
Summary Yeast cell wall assembly is a highly regulated and dynamic process. A class of surface aspartic peptidases anchored by glycosylphosphatidylinositol (GPI) group, collectively known as yapsins, was proposed to be involved in construction. The Saccharomyces cerevisiae Yps1p, the prototypal yapsin, processed internally within loop region produce an α/β two‐subunit enzyme. Here we investigated activation mechanism GPI‐anchored Yps1p identified some its substrates. We report that all steps...
Understanding the function of cellular systems requires describing how proteins assemble with each other into transient and stable complexes to determine their spatial relationships. Among tools available perform these analyses on a large scale is Protein-fragment Complementation Assay based dihydrofolate reductase (DHFR PCA). Here we test longer linkers between fusion reporter fragments affect performance this assay. We investigate architecture RNA polymerases, proteasome conserved...
Abstract Antimicrobial resistance (AMR) is a global threat. To optimize the use of our antifungal arsenal, we need rapid detection and monitoring tools that rely on high-quality AMR mutation data. Here, performed thorough manual curation published mutations in fungal pathogens to produce FungAMR reference dataset. A total 462 papers were curated, leading 54,666 entries all classified with degree evidence supports their role resistance. covers 92 species, 202 genes 184 drugs. We combined...
Abstract Hybrids between species often show extreme phenotypes, including some that take place at the molecular level. In this study, we investigated phenotypes of an interspecies diploid hybrid in terms protein–protein interactions inferred from protein correlation profiling. We used two yeast species, Saccharomyces cerevisiae and uvarum, which are interfertile, but yet have proteins diverged enough to be differentiated using mass spectrometry. Most similar parents, consistent with assembly...
Abstract Whole-genome duplication (WGD) followed by speciation allows us to examine the parallel evolution of ohnolog pairs. In yeast family Saccharomycetaceae, HRR25 is a rare case repeated maintenance. This gene has reverted single copy in Saccharomyces cerevisiae where it now essential, but been maintained as pairs at least 7 species post-WGD. S. cerevisiae, encodes casein kinase 1δ/ε and plays role variety functions through its activity protein–protein interactions (PPIs). We...