194 research outputs found
A gene coevolution network provides insight to eukaryotic cellular and genomic structure and function
No full textdata associated with Steenwyk et al. 2022, An orthologous gene coevolution network provides insight into eukaryotic cellular and genomic structure and function
A robust phylogenomic timetree for biotechnologically and medically important fungi in the genera Aspergillus and Penicillium
No full textThis figshare repository contains all supplementary material, data, and other relevant files for the project A robust phylogenomic timetree for biotechnologically and medically important fungi in the genera Aspergillus and Penicillium by Steenwyk et al. 2019, mBio. Correspondence: antonis.rokas[at]vanderbilt.eduAbstractThe filamentous fungal family Aspergillaceae contains > 1,000 known species, mostly in the genera Aspergillus and Penicillium. Several species are used in the food, biotechnology, and drug industries (e.g., Aspergillus oryzae, Penicillium camemberti), while others are dangerous human and plant pathogens (e.g., Aspergillus fumigatus, Penicillium digitatum). To infer a robust phylogeny and pinpoint poorly resolved branches and their likely underlying contributors, we used 81 genomes spanning the diversity of Aspergillus and Penicillium to construct a 1,668-gene data matrix. Phylogenies of the nucleotide and amino acid versions of this full data matrix as well as of several additional data matrices were generated using three different maximum likelihood schemes (i.e., gene-partitioned, unpartitioned, and coalescence) and using both site-homogenous and site-heterogeneous models (total of 64 species-level phylogenies). Examination of the topological agreement among these phylogenies and measures of internode certainty identified 11 / 78 (14.1%) bipartitions that were incongruent and pinpointed the likely underlying contributing factors, which included incomplete lineage sorting, hidden paralogy, hybridization or introgression, and reconstruction artifacts associated with poor taxon sampling. Relaxed molecular clock analyses suggest that Aspergillaceae likely originated in the lower Cretaceous and the Aspergillus and Penicillium genera in the upper Cretaceous. Our results shed light on the ongoing debate on Aspergillus systematics and taxonomy and provide a robust evolutionary and temporal framework for comparative genomic analyses in Aspergillaceae. More broadly, our approach provides a general template for phylogenomic identification of resolved and contentious branches in densely genome-sequenced lineages across the tree of life.ImportanceUnderstanding the evolution of traits across technologically and medically significant fungi requires a robust phylogeny. Even though species in the Aspergillus and Penicillium genera (Family: Aspergillaceae, Class: Eurotiomycetes) are some of the most significant technologically and medically relevant fungi, we still lack a genome-scale phylogeny of the lineage or knowledge of the parts of the phylogeny that exhibit conflict among analyses. Here, we used a phylogenomic approach to infer evolutionary relationships among 81 genomes that span the diversity of Aspergillus and Penicillium species, to identify conflicts in the phylogeny, and to determine the likely underlying factors of the observed conflicts. Using a data matrix comprised of 1,668 genes, we found that while most branches of the phylogeny of the Aspergillaceae are robustly supported and recovered irrespective of method of analysis, a few exhibit varying degrees of conflict among our analyses. Further examination of the observed conflict revealed that it largely stems from incomplete lineage sorting and hybridization or introgression. Our analyses provide a robust and comprehensive evolutionary genomic roadmap for this important lineage, which will facilitate the examination of the diverse technologically and medically relevant traits of these fungi in an evolutionary context.</div
Variation Among Biosynthetic Gene Clusters, Secondary Metabolite Profiles, and Cards of Virulence Across Aspergillus Species
No full textThe Generation, Exploitation and Future of Induced Pluripotent Stem Cells
No full textThe foundational advancements of John Gurdon and Shinya Yamanaka have improved understanding of dedifferen- tiation of cells to a pluripotent state. The seminal discovery established a novel system to study disease pathogenesis, drug screening, and toxicity, as well as sprouted the new field of regenerative medicine. In this article, the method- ology to obtain dedifferentiated cells, known as induced pluripotent stem (iPS) cells, subsequent validation, and application of which are reviewed. The experiments investigated here aim to demonstrate the capacity of iPS cells to replace the ethically-gray human embryonic cells by developing human livers and viable, healthy animals. It is con- cluded that the reported methods pave the way for a bright future of iPS cell application in both basic and applied sciences
CryptoCEN data v1.0.0
No full textData forMJ O'Meara, JR Rapala, CB Nichols, C Alexandre, B Billmyre, JL Steenwyk, A Alspaugh, TR O'MearaCryptoCEN: A Co-Expression Network for Cryptococcus neoformans reveals novel proteins involved in DNA damage repairCode available at https://github.com/maomlab/CalCEN/tree/master/vignettes/CryptoCENh99_transcript_annotations.tsvCryptococcus neoforman H99 (NCBI Taxon:235443) annotated protein features collected from FungiDB Release 49top_coexp_hits.tsvtop 50 CrypoCEN associations for each genetop_coexp_hits_0.05.tsvtop CrypoCEN associations for each gene filtered by score > 0.95 and at most 50 per geneData/estimated_expression_meta.tsvMetadata for RNAseq estimated expression runsData/estimated_expression.tsvgene by RNA-seq run estimated expressionData/sac_complex_interactions.tsvC. neoformans genes that are orthologous to S. cerevisiae genes who's proteins are involved in a protein complexNetworks/CryptoCEN_network.tsvCo-expression networkNetworks/BlastP_network.tsvProtein sequence similarity networkNetwork/CoEvo_network.tsvCo-evolution network</ul
A portrait of budding yeasts: A symbol of the arts, sciences and a whole greater than the sum of its parts
No full textOrthoSNAP: a tree splitting and pruning algorithm for retrieving single-copy orthologs from gene family trees
No full text Molecular evolution studies, such as phylogenomic studies and genome-wide surveys of selection, often rely on gene families of single-copy orthologs (SC-OGs). Large gene families with multiple homologs in one or more species—a phenomenon observed among several important families of genes such as transporters and transcription factors—are often ignored because identifying and retrieving SC-OGs nested within them is challenging. To address this issue and increase the number of markers used in molecular evolution studies, we developed OrthoSNAP, a software that uses a phylogenetic framework to simultaneously split gene families into SC-OGs and prune species-specific inparalogs. We term SC-OGs identified by OrthoSNAP as SNAP-OGs because they are identified using a splitting and pruning procedure analogous to snapping branches on a tree. From 415,129 orthologous groups of genes inferred across seven eukaryotic phylogenomic datasets, we identified 9,821 SC-OGs; using OrthoSNAP on the remaining 405,308 orthologous groups of genes, we identified an additional 10,704 SNAP-OGs. Comparison of SNAP-OGs and SC-OGs revealed that their phylogenetic information content was similar, even in complex datasets that contain a whole genome duplication, complex patterns of duplication and loss, transcriptome data where each gene typically has multiple transcripts, and contentious branches in the tree of life. OrthoSNAP is useful for increasing the number of markers used in molecular evolution data matrices, a critical step for robustly inferring and exploring the tree of life. </p
Nutritional Heterogeneity Among Aspergillus fumigatus Strains Has Consequences for Virulence in a Strain- and Host-Dependent Manner
No full textOnly Vanderbilt University affiliated authors are listed on VUIR. For a full list of authors, access the version of record at https://www.frontiersin.org/articles/10.3389/fmicb.2019.00854/fullAcquisition and subsequent metabolism of different carbon and nitrogen sources have been shown to play an important role in virulence attributes of the fungal pathogen Aspergillus fumigatus, such as the secretion of host tissue-damaging proteases and fungal cell wall integrity. We examined the relationship between the metabolic processes of carbon catabolite repression (CCR), nitrogen catabolite repression (NCR) and virulence in a variety of A. fumigatus clinical isolates. A considerable amount of heterogeneity with respect to the degree of CCR and NCR was observed and a positive correlation between NCR and virulence in a neutropenic mouse model of pulmonary aspergillosis (PA) was found. Isolate Afs35 was selected for further analysis and compared to the reference strain A1163, with both strains presenting the same degree of virulence in a neutropenic mouse model of PA. Afs35 metabolome analysis in physiological-relevant carbon sources indicated an accumulation of intracellular sugars that also serve as cell wall polysaccharide precursors. Genome analysis showed an accumulation of missense substitutions in the regulator of protease secretion and in genes encoding enzymes required for cell wall sugar metabolism. Based on these results, the virulence of strains Afs35 and A1163 was assessed in a triamcinolone murine model of PA and found to be significantly different, confirming the known importance of using different mouse models to assess strain-specific pathogenicity. These results highlight the importance of nitrogen metabolism for virulence and provide a detailed example of the heterogeneity that exists between A. fumigatus isolates with consequences for virulence in a strain-specific and host-dependent manner.JO was supported in part by institutional startup funds and in part through the Dartmouth Lung Biology Center for Molecular, Cellular, and Translational Research grant P30 GM106394 (PI: Bruce A. Stanton) and Center for Molecular, Cellular, and Translational Immunological Research grant P30 GM103415 (PI: William R. Green). FA was supported by a FAPESP young researcher fellowship (2016/03322-7). LR was supported by a FAPESP young researcher fellowship (2017/14159-2). JS was supported by the Graduate Program in Biological Sciences at Vanderbilt University and AR was supported, in part, by the National Science Foundation (DEB-1442113), the Vanderbilt Discovery Grant Program, the Burroughs Wellcome Fund, and the Guggenheim Foundation
Extensive Copy Number Variation in Fermentation-Related Genes Among Saccharomyces cerevisiae Wine Strains
No full textDue to the importance of Saccharomyces cerevisiae in wine-making, the genomic variation of wine yeast strains has been extensively studied. One of the major insights stemming from these studies is that wine yeast strains harbor low levels of genetic diversity in the form of single nucleotide polymorphisms (SNPs). Genomic structural variants, such as copy number (CN) variants, are another major type of variation segregating in natural populations. To test whether genetic diversity in CN variation is also low across wine yeast strains, we examined genome-wide levels of CN variation in 132 whole-genome sequences of S. cerevisiae wine strains. We found an average of 97.8 CN variable regions (CNVRs) affecting ∼4% of the genome per strain. Using two different measures of CN diversity, we found that gene families involved in fermentation-related processes such as copper resistance (CUP), flocculation (FLO), and glucose metabolism (HXT), as well as the SNO gene family whose members are expressed before or during the diauxic shift, showed substantial CN diversity across the 132 strains examined. Importantly, these same gene families have been shown, through comparative transcriptomic and functional assays, to be associated with adaptation to the wine fermentation environment. Our results suggest that CN variation is a substantial contributor to the genomic diversity of wine yeast strains, and identify several candidate loci whose levels of CN variation may affect the adaptation and performance of wine yeast strains during fermentation
Extensive Copy Number Variation in Fermentation-Related Genes among<i>Saccharomyces cerevisiae</i>Wine Strains
No full textAbstractDue to the importance ofSaccharomyces cerevisiaein wine-making, the genomic variation of wine yeast strains has been extensively studied. One of the major insights stemming from these studies is that wine yeast strains harbor low levels of genetic diversity in the form of single nucleotide polymorphisms (SNPs). Genomic structural variants, such as copy number (CN) variants, are another major type of variation segregating in natural populations. To test whether genetic diversity in CN variation is also low across wine yeast strains, we examined genome-wide levels of CN variation in 132 whole-genome sequences ofS. cerevisiaewine strains. We found an average of 97.8 CN variable regions (CNVRs) affecting ~4% of the genome per strain. Using two different measures of CN diversity, we found that gene families involved in fermentation-related processes such as copper resistance (CUP), flocculation (FLO), and glucose metabolism (HXT), as well as theSNOgene family whose members are expressed before or during the diauxic shift showed substantial CN diversity across the 132 strains examined. Importantly, these same gene families have been shown, through comparative transcriptomic and functional assays, to be associated with adaptation to the wine fermentation environment. Our results suggest that CN variation is a substantial contributor to the genomic diversity of wine yeast strains and identify several candidate loci whose levels of CN variation may affect the adaptation and performance of wine yeast strains during fermentation.</jats:p
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