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

Janbon, Guilhem and Ormerod, Kate L and Paulet, Damien and Byrnes, Edmond J and Yadav, Vikas and Chatterjee, Gautam and Mullapudi, Nandita and Hon, Chung-Chau and Billmyre, Blake R and Brunel, Francois and Bahn, Yong-Sun and Chen, Weidong and Chen, Yuan and Chow, Eve WL and Coppee, Jean-Yves and Floyd-Averette, Anna and Gaillardin, Claude and Gerik, Kimberly J and Goldberg, Jonathan and Gonzalez-Hilarion, Sara and Gujja, Sharvari and Hamlin, Joyce L and Hsueh, Yen-Ping and Ianiri, Giuseppe and Jones, Steven and Kodira, Chinnappa D and Kozubowski, Lukasz and Lam, Woei and Marra, Marco and Mesner, Larry D and Mieczkowski, Piotr A and Moyrand, Frederique and Nielsen, Kirsten and Proux, Caroline and Rossignol, Tristan and Schein, Jacqueline E and Sun, Sheng and Wollschlaeger, Carolin and Wood, Ian A and Zeng, Qiandong and Neuveglise, Cecile and Newlon, Carol S and Perfect, John R and Lodge, Jennifer K and Idnurm, Alexander and Stajich, Jason E. and Kronstad, James W. and Sanyal, Kaustuv and Heitman, Joseph and Fraser, James A and 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. In: PLOS GENETICS, 10 (4).

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Official URL: http://dx.doi.org/10.1371/journal.pgen.1004261

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.

Item Type: Journal Article
Additional Information: copyright for this article belongs to PUBLIC LIBRARY SCIENCE, 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
Department/Centre: Division of Physical & Mathematical Sciences > Mathematics
Depositing User: Id for Latest eprints
Date Deposited: 24 Jun 2014 07:33
Last Modified: 24 Jun 2014 07:33
URI: http://eprints.iisc.ac.in/id/eprint/49324

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