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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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Date
2014-04
Authors
Janbon, G
Ormerod, KL
Paulet, D
Byrnes, EJ
Yadav, V
Chatterjee, G
Mullapudi, N
Hon, C
Billmyre, RB
Brunel, F
Bahn, Y
Chen, W
Chen, Y
Chow, EWL
Coppée, J
Floyd-Averette, A
Gaillardin, C
Gerik, KJ
Goldberg, J
Gonzalez-Hilarion, S
Gujja, S
Hamlin, JL
Hsueh, Y
Ianiri, G
Jones, S
Kodira, CD
Kozubowski, L
Lam, W
Marra, M
Mesner, LD
Mieczkowski, PA
Moyrand, F
Nielsen, K
Proux, C
Rossignol, T
Schein, JE
Sun, S
Wollschlaeger, C
Wood, IA
Zeng, Q
Neuvéglise, C
Newlon, CS
Perfect, JR
Lodge, JK
Idnurm, A
Stajich, JE
Kronstad, JW
Sanyal, K
Heitman, J
Fraser, JA
Cuomo, CA
Dietrich, FS
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Abstract
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.
Type
Journal article
Subject
Chromosomes, Fungal
Cryptococcus neoformans
DNA, Fungal
Genome, Fungal
Introns
RNA, Fungal
Transcriptome
Virulence
Permalink
https://hdl.handle.net/10161/8468
Published Version (Please cite this version)
10.1371/journal.pgen.1004261
Publication Info
Janbon, G; Ormerod, KL; Paulet, D; Byrnes, EJ; Yadav, V; Chatterjee, G; ... Dietrich, FS (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.
This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.
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Scholars@Duke

Dietrich

Fred Samuel Dietrich

Associate Professor of Molecular Genetics and Microbiology
My laboratory is interested in fungal genomics.In particular we use genomic sequencing of fungal strains and species in comparative analysis. Starting with the sequencing of Saccharomyces cerevisiae strain S288C, I have been involved in the genome sequencing and annotation of Ashbya gossypii, Cryptococcus neoformans var. grubii and ~100 additional S. cerevisiae strains. We currently use Illumina paired end and mate paired sequencin
Heitman

Joseph Heitman

Chair, Department of Molecular Genetics and Microbiology
Joseph Heitman was an undergraduate at the University of Chicago (1980-1984), graduating from the BS-MS program with dual degrees in chemistry and biochemistry with general and special honors. He then matriculated as an MD-PhD student at Cornell and Rockefeller Universities and worked with Peter Model and Norton Zinder on how restriction enzymes recognize specific DNA sequences and how bacteria respond to and repair DNA breaks and nicks. Dr. Heitman moved as an EMBO long-term fellow to the Bi
Lodge

Jennifer Lodge

Vice President for Research and Innovation
Perfect

John Robert Perfect

James B. Duke Distinguished 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
Yadav

Vikas Yadav

Research Associate, Senior
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