Analysis of the genome and transcriptome of Cryptococcus neoformans var. grubii reveals complex RNA expression and microevolution leading to virulence attenuation.
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 articleSubject
Chromosomes, FungalCryptococcus neoformans
DNA, Fungal
Genome, Fungal
Introns
RNA, Fungal
Transcriptome
Virulence
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https://hdl.handle.net/10161/8468Published Version (Please cite this version)
10.1371/journal.pgen.1004261Publication 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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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
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
Jennifer Lodge
Vice President for Research and Innovation
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
Vikas Yadav
Research Associate, Senior
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