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Massoumi Alamouti S.,University of British Columbia | Haridas S.,University of British Columbia | Haridas S.,U.S. Department of Energy | Feau N.,University of British Columbia | And 3 more authors.
Molecular Biology and Evolution | Year: 2014

Studies on beetle/tree fungal symbionts typically characterize the ecological and geographic distributions of the fungal populations. There is limited understanding of the genome-wide evolutionary processes that act within and between species as such fungi adapt to different environments, leading to physiological differences and reproductive isolation. Here, we assess genomic evidence for such evolutionary processes by extending our recent work on Grosmannia clavigera, which is vectored by the mountain pine beetle and jeffrey pine beetle. We report the genome sequences of an additional 11 G. clavigera (Gc) sensu lato strains from the two known sibling species, Grosmannia sp. (Gs) and Gc. The 12 fungal genomes are structurally similar, showing large-scale synteny within and between species. We identified 103,430 single-nucleotide variations that separated the Grosmannia strains into divergent Gs and Gc clades, and further divided each of these clades into two subclades, one of which may represent an additional species. Comparing variable genes between these lineages, we identified truncated genes and potential pseudogenes, as well as seven genes that show evidence of positive selection. As these variable genes are involved in secondary metabolism and in detoxifying or utilizing host-tree defense chemicals (e.g., polyketide synthases, oxidoreductases, and mono-oxygenases), their variants may reflect adaptation to the specific chemistries of the host trees Pinus contorta, P. ponderosa, and P. jeffreyi. This work provides a comprehensive resource for developing informative markers for landscape population genomics of these ecologically and economically important fungi, and an approach that could be extended to other beetle-tree-associated fungi. © 2014 The Author. Source

Qin Z.S.,Emory University | Bilenky M.,British Columbia Cancer Agency Genome science Center | Su G.,University of Michigan | Jones S.J.M.,British Columbia Cancer Agency Genome science Center
Frontiers in Bioscience - Elite | Year: 2013

Assembling a comprehensive catalog of all transcription factors (TFs) and the genes that they regulate (regulon) is important for understanding gene regulation. The sequence-specific conserved binding profiles of TFs can be characterized from whole genome sequences with phylogenetic approaches, and a large number of such profiles have been released. Effective mining of these data sources could reveal novel functional elements computationally. Due to the variability of the binding sites, it is necessary to generalize profiles pertinent to the same TF by clustering. The summarized familial profile is effective in identifying unknown binding sites, thus lead to gene co-regulation prediction. Here we report MotifOrganizer, a scalable model-based clustering algorithm designed for grouping motifs identified from large scale comparative genomics studies on mammalian species. The new algorithm allows grouping of motifs with variable widths and a novel two-stage operation scheme further increases the scalability. MotifOrgainzer demonstrated favorable performance comparing to distance-based and single-stage model-based clustering tools on simulated data. Tests on approximately 150k motifs from the cisRED human database demonstrated that MotifOrganizer can effectively cluster whole genome sets of mammalian motifs. Source

Rebollo R.,Terry Fox Laboratory | Rebollo R.,University of British Columbia | Karimi M.M.,University of British Columbia | Bilenky M.,British Columbia Cancer Agency Genome science Center | And 14 more authors.
PLoS Genetics | Year: 2011

The "arms race" relationship between transposable elements (TEs) and their host has promoted a series of epigenetic silencing mechanisms directed against TEs. Retrotransposons, a class of TEs, are often located in repressed regions and are thought to induce heterochromatin formation and spreading. However, direct evidence for TE-induced local heterochromatin in mammals is surprisingly scarce. To examine this phenomenon, we chose two mouse embryonic stem (ES) cell lines that possess insertionally polymorphic retrotransposons (IAP, ETn/MusD, and LINE elements) at specific loci in one cell line but not the other. Employing ChIP-seq data for these cell lines, we show that IAP elements robustly induce H3K9me3 and H4K20me3 marks in flanking genomic DNA. In contrast, such heterochromatin is not induced by LINE copies and only by a minority of polymorphic ETn/MusD copies. DNA methylation is independent of the presence of IAP copies, since it is present in flanking regions of both full and empty sites. Finally, such spreading into genes appears to be rare, since the transcriptional start sites of very few genes are less than one Kb from an IAP. However, the B3galtl gene is subject to transcriptional silencing via IAP-induced heterochromatin. Hence, although rare, IAP-induced local heterochromatin spreading into nearby genes may influence expression and, in turn, host fitness. © 2011 Rebollo et al. Source

Cusulin C.,University of Calgary | Chesnelong C.,University of Calgary | Bose P.,British Columbia Cancer Agency Genome science Center | Bilenky M.,British Columbia Cancer Agency Genome science Center | And 7 more authors.
Stem Cell Reports | Year: 2015

In glioblastoma multiforme (GBM), brain-tumor-initiating cells (BTICs) with cancer stem cell characteristics have been identified and proposed as primordial cells responsible for disease initiation, recurrence, and therapeutic resistance. However, the extent to which individual, patient-derived BTIC lines reflect the heterogeneity of GBM remains poorly understood. Here we applied a stem cell biology approach and compared self-renewal, marker expression, label retention, and asymmetric cell division in 20 BTIC lines. Through cluster analysis, we identified two subgroups of BTIC lines with distinct precursor states, stem- or progenitor-like, predictive of survival after xenograft. Moreover, stem and progenitor transcriptomic signatures were identified, which showed a strong association with the proneural and mesenchymal subtypes, respectively, in the TCGA cohort. This study proposes a different framework for the study and use of BTIC lines and provides precursor biology insights into GBM. © 2015 The Authors. Source

Hall D.E.,University of British Columbia | Yuen M.M.S.,University of British Columbia | Jancsik S.,University of British Columbia | Quesada A.L.,University of British Columbia | And 12 more authors.
BMC Plant Biology | Year: 2013

Background: The mountain pine beetle (MPB, Dendroctonus ponderosae) epidemic has affected lodgepole pine (Pinus contorta) across an area of more than 18 million hectares of pine forests in western Canada, and is a threat to the boreal jack pine (Pinus banksiana) forest. Defence of pines against MPB and associated fungal pathogens, as well as other pests, involves oleoresin monoterpenes, which are biosynthesized by families of terpene synthases (TPSs). Volatile monoterpenes also serve as host recognition cues for MPB and as precursors for MPB pheromones. The genes responsible for terpene biosynthesis in jack pine and lodgepole pine were previously unknown.Results: We report the generation and quality assessment of assembled transcriptome resources for lodgepole pine and jack pine using Sanger, Roche 454, and Illumina sequencing technologies. Assemblies revealed transcripts for approximately 20,000 - 30,000 genes from each species and assembly analyses led to the identification of candidate full-length prenyl transferase, TPS, and P450 genes of oleoresin biosynthesis. We cloned and functionally characterized, via expression of recombinant proteins in E. coli, nine different jack pine and eight different lodgepole pine mono-TPSs. The newly identified lodgepole pine and jack pine mono-TPSs include (+)-α-pinene synthases, (-)-α-pinene synthases, (-)-β-pinene synthases, (+)-3-carene synthases, and (-)-β-phellandrene synthases from each of the two species.Conclusion: In the absence of genome sequences, transcriptome assemblies are important for defence gene discovery in lodgepole pine and jack pine, as demonstrated here for the terpenoid pathway genes. The product profiles of the functionally annotated mono-TPSs described here can account for the major monoterpene metabolites identified in lodgepole pine and jack pine. © 2013 Hall et al.; licensee BioMed Central Ltd. Source

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