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PLoS Genet. 2014 Apr 17;10(4):e1004261. doi: 10.1371/journal.pgen.1004261. eCollection 2014 Apr.

Analysis of the genome and transcriptome of Cryptococcus neoformans var. grubii reveals complex RNA expression and microevolution leading to virulence attenuation.

Author information

1
Institut Pasteur, Unité Biologie et Pathogénicité Fongiques, Département Génomes et Génétique, Paris, France; INRA, USC2019, Paris, France.
2
University of Queensland, School of Chemistry and Molecular Biosciences, Brisbane, Queensland, Australia.
3
Institut Pasteur, Plate-forme Transcriptome et Epigénome, Département Génomes et Génétique, Paris, France.
4
Duke University Medical Center, Department of Molecular Genetics and Microbiology, Durham, North Carolina, United States of America.
5
Jawaharlal Nehru Centre for Advanced Scientific Research, Molecular Biology and Genetics Unit, Bangalore, India.
6
Genotypic Technology Private Limited, Bangalore, India.
7
Institut Pasteur, Unité Biologie Cellulaire du Parasitisme, Département Biologie Cellulaire et Infection, Paris, France.
8
INRA, UMR 1319 Micalis, Jouy-en-Josas, France.
9
Yonsei University, Center for Fungal Pathogenesis, Department of Biotechnology, Seoul, Republic of Korea.
10
Rutgers New Jersey Medical School, Department of Microbiology and Molecular Genetics, Newark, New Jersey, United States of America.
11
Washington University School of Medicine, Department of Molecular Microbiology, St. Louis, Missouri, United States of America.
12
Broad Institute of MIT and Harvard, Cambridge, Massachusetts, United States of America.
13
University of Virginia, Department of Biochemistry and Molecular Genetics, Charlottesville, Virginia, United States of America.
14
Duke University Medical Center, Department of Molecular Genetics and Microbiology, Durham, North Carolina, United States of America; California Institute of Technology, Division of Biology, Pasadena, California, United States of America.
15
University of Missouri-Kansas City, School of Biological Sciences, Division of Cell Biology and Biophysics, Kansas City, Missouri, United States of America.
16
Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia, Canada.
17
Clemson University, Department of Genetics and Biochemistry, Clemson, South Carolina, United States of America.
18
University of North Carolina, Department of Genetics, Chapel Hill, North Carolina, United States of America.
19
Duke University Medical Center, Department of Molecular Genetics and Microbiology, Durham, North Carolina, United States of America; University of Minnesota, Microbiology Department, Minneapolis, Minnesota, United States of America.
20
University of Queensland, School of Mathematics and Physics, Brisbane, Queensland, Australia.
21
Duke University Medical Center, Duke Department of Medicine and Molecular Genetics and Microbiology, Durham, North Carolina, United States of America.
22
Duke University Medical Center, Department of Molecular Genetics and Microbiology, Durham, North Carolina, United States of America; University of California, Department of Plant Pathology & Microbiology, Riverside, California, United States of America.
23
Michael Smith Laboratories, Department of Microbiology and Immunology, Vancouver, British Columbia, Canada.

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.

PMID:
24743168
PMCID:
PMC3990503
DOI:
10.1371/journal.pgen.1004261
[Indexed for MEDLINE]
Free PMC Article

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