Analysis of the Genome and Transcriptome of Cryptococcus neoformans var. grubii Reveals Complex RNA Expression and Microevolution Leading to Virulence Attenuation

Guilhem Janbon, Kate L. Ormerod, Damien Paulet, Edmond J. Byrnes, Vikas Yadav, Gautam Chatterjee, Nandita Mullapudi, Chung Chau Hon, R. Blake Billmyre, François Brunel, Yong Sun Bahn, Weidong Chen, Yuan Chen, Eve W.L. Chow, Jean Yves Coppée, Anna Floyd-Averette, Claude Gaillardin, Kimberly J. Gerik, Jonathan Goldberg, Sara Gonzalez-HilarionSharvari Gujja, Joyce L. Hamlin, Yen Ping Hsueh, Giuseppe Ianiri, Steven Jones, Chinnappa D. Kodira, Lukasz Kozubowski, Woei Lam, Marco Marra, Larry D. Mesner, Piotr A. Mieczkowski, Frédérique Moyrand, Kirsten Nielsen, Caroline Proux, Tristan Rossignol, Jacqueline E. Schein, Sheng Sun, Carolin Wollschlaeger, Ian A. Wood, Qiandong Zeng, Cécile Neuvéglise, Carol S. Newlon, John R. Perfect, Jennifer K. Lodge, Alexander Idnurm, Jason E. Stajich, James W. Kronstad, Kaustuv Sanyal, Joseph Heitman, James A. Fraser, Christina A. Cuomo, Fred S. Dietrich

Research output: Contribution to journalArticle

166 Citations (Scopus)

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.

Original languageEnglish
Article numbere1004261
JournalPLoS Genetics
Volume10
Issue number4
DOIs
Publication statusPublished - 2014 Apr

Fingerprint

Cryptococcus neoformans
Gene Expression Profiling
virulence
transcriptome
Introns
Virulence
RNA
introns
Poly A
genome
Genome
mutation
Untranslated Regions
replication origin
Polyadenylation
Mutation
Replication Origin
Centromere
gene
centromeres

All Science Journal Classification (ASJC) codes

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics
  • Genetics(clinical)
  • Cancer Research

Cite this

Janbon, Guilhem ; Ormerod, Kate L. ; Paulet, Damien ; Byrnes, 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, Frédérique ; 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. / Analysis of the Genome and Transcriptome of Cryptococcus neoformans var. grubii Reveals Complex RNA Expression and Microevolution Leading to Virulence Attenuation. In: PLoS Genetics. 2014 ; Vol. 10, No. 4.
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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.",
author = "Guilhem Janbon and Ormerod, {Kate L.} and Damien Paulet and Byrnes, {Edmond J.} and Vikas Yadav and Gautam Chatterjee and Nandita Mullapudi and Hon, {Chung Chau} and Billmyre, {R. Blake} and Fran{\cc}ois Brunel and Bahn, {Yong Sun} and Weidong Chen and Yuan Chen and Chow, {Eve W.L.} and Copp{\'e}e, {Jean Yves} and Anna Floyd-Averette and Claude Gaillardin and Gerik, {Kimberly J.} and Jonathan Goldberg and Sara Gonzalez-Hilarion and Sharvari Gujja and Hamlin, {Joyce L.} and Hsueh, {Yen Ping} and Giuseppe Ianiri and Steven Jones and Kodira, {Chinnappa D.} and Lukasz Kozubowski and Woei Lam and Marco Marra and Mesner, {Larry D.} and Mieczkowski, {Piotr A.} and Fr{\'e}d{\'e}rique Moyrand and Kirsten Nielsen and Caroline Proux and Tristan Rossignol and Schein, {Jacqueline E.} and Sheng Sun and Carolin Wollschlaeger and Wood, {Ian A.} and Qiandong Zeng and C{\'e}cile Neuv{\'e}glise and Newlon, {Carol S.} and Perfect, {John R.} and Lodge, {Jennifer K.} and Alexander Idnurm and Stajich, {Jason E.} and Kronstad, {James W.} and Kaustuv Sanyal and Joseph Heitman and Fraser, {James A.} and Cuomo, {Christina A.} and Dietrich, {Fred S.}",
year = "2014",
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doi = "10.1371/journal.pgen.1004261",
language = "English",
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Janbon, G, Ormerod, KL, Paulet, D, Byrnes, EJ, Yadav, V, Chatterjee, G, Mullapudi, N, Hon, CC, Billmyre, RB, Brunel, F, Bahn, YS, Chen, W, Chen, Y, Chow, EWL, Coppée, JY, Floyd-Averette, A, Gaillardin, C, Gerik, KJ, Goldberg, J, Gonzalez-Hilarion, S, Gujja, S, Hamlin, JL, Hsueh, YP, 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 2014, 'Analysis of the Genome and Transcriptome of Cryptococcus neoformans var. grubii Reveals Complex RNA Expression and Microevolution Leading to Virulence Attenuation', PLoS Genetics, vol. 10, no. 4, e1004261. https://doi.org/10.1371/journal.pgen.1004261

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, 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, Frédérique; 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.

In: PLoS Genetics, Vol. 10, No. 4, e1004261, 04.2014.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Analysis of the Genome and Transcriptome of Cryptococcus neoformans var. grubii Reveals Complex RNA Expression and Microevolution Leading to Virulence Attenuation

AU - Janbon, Guilhem

AU - Ormerod, Kate L.

AU - Paulet, Damien

AU - Byrnes, Edmond J.

AU - Yadav, Vikas

AU - Chatterjee, Gautam

AU - Mullapudi, Nandita

AU - Hon, Chung Chau

AU - Billmyre, R. Blake

AU - Brunel, François

AU - Bahn, Yong Sun

AU - Chen, Weidong

AU - Chen, Yuan

AU - Chow, Eve W.L.

AU - Coppée, Jean Yves

AU - Floyd-Averette, Anna

AU - Gaillardin, Claude

AU - Gerik, Kimberly J.

AU - Goldberg, Jonathan

AU - Gonzalez-Hilarion, Sara

AU - Gujja, Sharvari

AU - Hamlin, Joyce L.

AU - Hsueh, Yen Ping

AU - Ianiri, Giuseppe

AU - Jones, Steven

AU - Kodira, Chinnappa D.

AU - Kozubowski, Lukasz

AU - Lam, Woei

AU - Marra, Marco

AU - Mesner, Larry D.

AU - Mieczkowski, Piotr A.

AU - Moyrand, Frédérique

AU - Nielsen, Kirsten

AU - Proux, Caroline

AU - Rossignol, Tristan

AU - Schein, Jacqueline E.

AU - Sun, Sheng

AU - Wollschlaeger, Carolin

AU - Wood, Ian A.

AU - Zeng, Qiandong

AU - Neuvéglise, Cécile

AU - Newlon, Carol S.

AU - Perfect, John R.

AU - Lodge, Jennifer K.

AU - Idnurm, Alexander

AU - Stajich, Jason E.

AU - Kronstad, James W.

AU - Sanyal, Kaustuv

AU - Heitman, Joseph

AU - Fraser, James A.

AU - Cuomo, Christina A.

AU - Dietrich, Fred S.

PY - 2014/4

Y1 - 2014/4

N2 - 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.

AB - 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.

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