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

Janbon, Guilhem, Ormerod, Kate L., Paulet, Damien, Byrnes III, Edmond J., Yadav, Vikas, Chatterjee, Gautam, Mullapudi, Nandita, Hon, Chung-Chau, Billmyre, R. Blake, Brunel, François, Bahn, Yong-Sun, Chen, Weidong, Chen, Yuan, Chow, Eve W. L., Coppée, Jean-Yves, Floyd-Averette, Anna, Gaillardin, Claude, Gerik, Kimberly J., Goldberg, Jonathan, Gonzalez-Hilarion, Sara, Gujja, Sharvari, Hamlin, Joyce L., Hsueh, Yen-Ping, Ianiri, Giuseppe, Jones, Steven, Kodira, Chinnappa D., Kozubowski, Lukasz, Lam, Woei, Marra, Marco, Mesner, Larry D., Mieczkowski, Piotr A., Moyrand, Fréderique, Nielsen, Kirsten, Proux, Caroline, Rossignol, Tristan, Schein, Jacqueline E., Sun, Sheng, Wollschlaeger, Carolin, Wood, Ian A., Zeng, Qiandong, Neuvéglise, Cécile, Newlon, Carol S., Perfect, John R., Lodge, Jennifer K., Idnurm, Alexander, Stajich, Jason E., Kronstad, James W., Sanyal, Kaustuv, Heitman, Joseph, Fraser, James A., Cuomo, Christina A. and Dietrich, Fred S. (2014) Analysis of the genome and transcriptome of Cryptococcus neoformans var. grubii reveals complex RNA expression and microevolution leading to virulence attenuation. PLoS Genetics, 10 4: e1004261.1-e1004261.26. doi:10.1371/journal.pgen.1004261


Author Janbon, Guilhem
Ormerod, Kate L.
Paulet, Damien
Byrnes III, Edmond J.
Yadav, Vikas
Chatterjee, Gautam
Mullapudi, Nandita
Hon, Chung-Chau
Billmyre, R. Blake
Brunel, François
Bahn, Yong-Sun
Chen, Weidong
Chen, Yuan
Chow, Eve W. L.
Coppée, Jean-Yves
Floyd-Averette, Anna
Gaillardin, Claude
Gerik, Kimberly J.
Goldberg, Jonathan
Gonzalez-Hilarion, Sara
Gujja, Sharvari
Hamlin, Joyce L.
Hsueh, Yen-Ping
Ianiri, Giuseppe
Jones, Steven
Kodira, Chinnappa D.
Kozubowski, Lukasz
Lam, Woei
Marra, Marco
Mesner, Larry D.
Mieczkowski, Piotr A.
Moyrand, Fréderique
Nielsen, Kirsten
Proux, Caroline
Rossignol, Tristan
Schein, Jacqueline E.
Sun, Sheng
Wollschlaeger, Carolin
Wood, Ian A.
Zeng, Qiandong
Neuvéglise, Cécile
Newlon, Carol S.
Perfect, John R.
Lodge, Jennifer K.
Idnurm, Alexander
Stajich, Jason E.
Kronstad, James W.
Sanyal, Kaustuv
Heitman, Joseph
Fraser, James A.
Cuomo, Christina A.
Dietrich, Fred S.
Title Analysis of the genome and transcriptome of Cryptococcus neoformans var. grubii reveals complex RNA expression and microevolution leading to virulence attenuation
Formatted title
Analysis of the genome and transcriptome of Cryptococcus neoformans var. grubii reveals complex RNA expression and microevolution leading to virulence attenuation
Journal name PLoS Genetics   Check publisher's open access policy
ISSN 1553-7404
1553-7390
Publication date 2014-04-17
Year available 2014
Sub-type Article (original research)
DOI 10.1371/journal.pgen.1004261
Open Access Status DOI
Volume 10
Issue 4
Start page e1004261.1
End page e1004261.26
Total pages 26
Editor Michael Freitag
Place of publication San Francisco, CA, United States
Publisher Public Library of Science
Language eng
Subject 1105 Ecology, Evolution, Behavior and Systematics
1312 Molecular Biology
1311 Genetics
2716 Genetics (clinical)
1306 Cancer Research
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.
Formatted 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.
Keyword Genetics & Heredity
Genetics & Heredity
GENETICS & HEREDITY
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID U54HG003067
HHSN272200900018C
2010-BLAN-1620-01
R37 AI39115-16
R01 NS042263
455980
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: School of Mathematics and Physics
Official 2015 Collection
School of Chemistry and Molecular Biosciences
 
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Created: Tue, 06 May 2014, 01:25:10 EST by Mrs Louise Nimwegen on behalf of School of Chemistry & Molecular Biosciences