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

187 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

All Science Journal Classification (ASJC) codes

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

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    Janbon, G., Ormerod, K. L., Paulet, D., Byrnes, E. J., Yadav, V., Chatterjee, G., Mullapudi, N., Hon, C. C., Billmyre, R. B., Brunel, F., Bahn, Y. S., Chen, W., Chen, Y., Chow, E. W. L., Coppée, J. Y., Floyd-Averette, A., Gaillardin, C., Gerik, K. J., Goldberg, J., ... Dietrich, F. 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]. https://doi.org/10.1371/journal.pgen.1004261