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PLoS Genet DOI: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.

Publication TypeJournal Article
Year of Publication2014
AuthorsJanbon, G, Ormerod, KL, Paulet, D, Byrnes, EJ, Yadav, V, Chatterjee, G, Mullapudi, N, Hon, C-C, R Billmyre, B, Brunel, F, Bahn, Y-S, Chen, W, Chen, Y, Chow, EWL, Coppée, J-Y, Floyd-Averette, A, Gaillardin, C, Gerik, KJ, Goldberg, J, Gonzalez-Hilarion, S, Gujja, S, Hamlin, JL, Hsueh, Y-P, 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
JournalPLoS Genet
Volume10
Issue4
Pagese1004261
Date Published2014 Apr
ISSN1553-7404
KeywordsChromosomes, Fungal, Cryptococcus neoformans, DNA, Fungal, Genome, Fungal, Introns, RNA, Fungal, Transcriptome, Virulence
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.

URLhttp://dx.plos.org/10.1371/journal.pgen.1004261
DOI10.1371/journal.pgen.1004261
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/24743168?dopt=Abstract

Alternate JournalPLoS Genet.
PubMed ID24743168
PubMed Central IDPMC3990503
Grant ListR37 AI039115 / AI / NIAID NIH HHS / United States
R01 AI073896 / AI / NIAID NIH HHS / United States
R01 AI093257 / AI / NIAID NIH HHS / United States
U54 HG003067 / HG / NHGRI NIH HHS / United States
T32 GM007754 / GM / NIGMS NIH HHS / United States
T32 GM007184 / GM / NIGMS NIH HHS / United States
AI50113-10 / AI / NIAID NIH HHS / United States
U54HG003067 / HG / NHGRI NIH HHS / United States
AI39115-16 / AI / NIAID NIH HHS / United States
R01 AI053721 / AI / NIAID NIH HHS / United States
R01 AI050184 / AI / NIAID NIH HHS / United States
T32 AI052080 / AI / NIAID NIH HHS / United States
R01 AI080275 / AI / NIAID NIH HHS / United States
R01 AI050113 / AI / NIAID NIH HHS / United States
AI094364 / AI / NIAID NIH HHS / United States
R03 AI105636 / AI / NIAID NIH HHS / United States
NS042263 / NS / NINDS NIH HHS / United States