Analysis of the genome and transcriptome of Cryptococcus neoformans var. grubii reveals complex RNA expression and microevolution leading to virulence attenuation.
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Cryptococcus neoformans is a pathogenic basidiomycetous yeast responsible for more than 600,000 deaths each year. It occurs as two serotypes (A and D) representing two varieties (i.e. grubii and neoformans, respectively). Here, we sequenced the genome and performed an RNA-Seq-based analysis of the C. neoformans var. grubii transcriptome structure. We determined the chromosomal locations, analyzed the sequence/structural features of the centromeres, and identified origins of replication. The genome was annotated based on automated and manual curation. More than 40,000 introns populating more than 99% of the expressed genes were identified. Although most of these introns are located in the coding DNA sequences (CDS), over 2,000 introns in the untranslated regions (UTRs) were also identified. Poly(A)-containing reads were employed to locate the polyadenylation sites of more than 80% of the genes. Examination of the sequences around these sites revealed a new poly(A)-site-associated motif (AUGHAH). In addition, 1,197 miscRNAs were identified. These miscRNAs can be spliced and/or polyadenylated, but do not appear to have obvious coding capacities. Finally, this genome sequence enabled a comparative analysis of strain H99 variants obtained after laboratory passage. The spectrum of mutations identified provides insights into the genetics underlying the micro-evolution of a laboratory strain, and identifies mutations involved in stress responses, mating efficiency, and virulence.
Published Version (Please cite this version)10.1371/journal.pgen.1004261
Publication InfoBahn, YS; Billmyre, RB; Brunel, F; Byrnes, EJ; Chatterjee, G; Chen, W; ... Zeng, Qiandong (2014). Analysis of the genome and transcriptome of Cryptococcus neoformans var. grubii reveals complex RNA expression and microevolution leading to virulence attenuation. PLoS Genet, 10(4). pp. e1004261. 10.1371/journal.pgen.1004261. Retrieved from https://hdl.handle.net/10161/8468.
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Chair, Department of Molecular Genetics and Microbiology
Signal transduction cascades regulating development and virulence of microorganisms Our research focuses on how cells sense their environment and communicate with other cells. We employ genetic and biochemical approaches to study two divergent single-celled eukaryotic organisms, the yeast Saccharomyces cerevisiae and the pathogenic fungus Cryptococcus neoformans. These organisms both grow as budding yeasts and appear quite similar, yet they have been diverging ov
James B. Duke Professor of Medicine
Research in my laboratory focuses around several aspects of medical mycology. We are investigating antifungal agents (new and old) in animal models of candida and cryptococcal infections. We have examined clinical correlation of in vitro antifungal susceptibility testing and with in vivo outcome. Our basic science project examines the molecular pathogenesis of cryptococcal infections. We have developed a molecular foundation for C. neoformans, including transformation systems, gene disr
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