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

被引：287

作者：

Janbon, Guilhem ^{[1
,2
]}

Ormerod, Kate L. ^{[3
]}

Paulet, Damien ^{[4
]}

Byrnes, Edmond J., III ^{[5
]}

Yadav, Vikas ^{[6
]}

Chatterjee, Gautam ^{[6
]}

Mullapudi, Nandita ^{[7
]}

Hon, Chung-Chau ^{[8
]}

Billmyre, R. Blake ^{[5
]}

Brunel, Francois ^{[9
]}

Bahn, Yong-Sun ^{[10
]}

Chen, Weidong ^{[11
]}

Chen, Yuan ^{[5
]}

Chow, Eve W. L. ^{[3
]}

Coppee, Jean-Yves ^{[4
]}

Floyd-Averette, Anna ^{[5
]}

Gaillardin, Claude ^{[9
]}

Gerik, Kimberly J. ^{[12
]}

Goldberg, Jonathan ^{[13
]}

Gonzalez-Hilarion, Sara ^{[1
,2
]}

Gujja, Sharvari ^{[13
]}

Hamlin, Joyce L. ^{[14
]}

Hsueh, Yen-Ping ^{[5
,15
]}

Ianiri, Giuseppe ^{[16
]}

Jones, Steven ^{[17
]}

Kodira, Chinnappa D. ^{[13
]}

Kozubowski, Lukasz ^{[18
]}

Lam, Woei ^{[12
]}

Marra, Marco ^{[17
]}

Mesner, Larry D. ^{[14
]}

Mieczkowski, Piotr A. ^{[19
]}

Moyrand, Frederique ^{[1
,2
]}

Nielsen, Kirsten ^{[5
,20
]}

Proux, Caroline ^{[4
]}

Rossignol, Tristan ^{[9
]}

Schein, Jacqueline E. ^{[17
]}

Sun, Sheng ^{[5
]}

Wollschlaeger, Carolin ^{[1
,2
]}

Wood, Ian A. ^{[21
]}

Zeng, Qiandong ^{[13
]}

Neuveglise, Cecile ^{[9
]}

Newlon, Carol S. ^{[11
]}

Perfect, John R. ^{[22
]}

Lodge, Jennifer K. ^{[12
]}

Idnurm, Alexander ^{[16
]}

Stajich, Jason E. ^{[5
,23
]}

Kronstad, James W. ^{[24
]}

Sanyal, Kaustuv ^{[6
]}

Heitman, Joseph ^{[5
]}

Fraser, James A. ^{[3
]}

机构：

[1] Inst Pasteur, Dept Genomes & Genet, Unite Biol & Pathogenicite Fong, Paris, France

[2] INRA, USC2019, Paris, France

[3] Univ Queensland, Sch Chem & Mol Biosci, Brisbane, Qld, Australia

[4] Inst Pasteur, Dept Genomes & Genet, Paris, France

[5] Duke Univ, Med Ctr, Dept Mol Genet & Microbiol, Durham, NC USA

[6] Indian Inst Sci, Jawaharlal Nehru Ctr Adv Sci Res, Mol Biol & Genet Unit, Bangalore 560012, Karnataka, India

[7] Genotyp Technol Private Ltd, Bangalore, Karnataka, India

[8] Inst Pasteur, Unite Biol Cellulaire Parasitisme, Dept Biol Cellulaire & Infect, Paris, France

[9] INRA, UMR Micalis 1319, Jouy En Josas, France

[10] Yonsei Univ, Ctr Fungal Pathogenesis, Dept Biotechnol, Seoul 120749, South Korea

[11] Rutgers New Jersey Med Sch, Dept Microbiol & Mol Genet, Newark, NJ USA

[12] Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA

[13] Broad Inst MIT & Harvard, Cambridge, MA USA

[14] Univ Virginia, Dept Biochem & Mol Genet, Charlottesville, VA USA

[15] CALTECH, Div Biol, Pasadena, CA 91125 USA

[16] Univ Missouri, Sch Biol Sci, Div Cell Biol & Biophys, Kansas City, MO 64110 USA

[17] BC Canc Agcy, Canadas Michael Smith Genome Sci Ctr, Vancouver, BC, Canada

[18] Clemson Univ, Dept Biochem & Genet, Clemson, SC USA

[19] Univ N Carolina, Dept Genet, Chapel Hill, NC USA

[20] Univ Minnesota, Dept Microbiol, Minneapolis, MN 55455 USA

[21] Univ Queensland, Sch Math & Phys, Brisbane, Qld, Australia

[22] Duke Univ, Med Ctr, Duke Dept Med & Mol Genet & Microbiol, Durham, NC USA

[23] Univ Calif Riverside, Dept Plant Pathol & Microbiol, Riverside, CA 92521 USA

[24] Michael Smith Labs, Dept Microbiol & Immunol, Vancouver, BC, Canada

来源：

PLOS GENETICS | 2014年 / 10卷 / 04期

基金：

澳大利亚国家健康与医学研究理事会; 美国国家卫生研究院;

关键词：

REPLICATION ORIGINS; FUNCTIONAL GENOMICS; CENTROMERE FUNCTION; CANDIDA-ALBICANS; GENE PREDICTION; DNA-SEQUENCES; SEXUAL CYCLE; SEQ DATA; 3' ENDS; YEAST;

D O I：

10.1371/journal.pgen.1004261

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

引用

页数：26

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