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Published Online January 13, 2005
Science DOI: 10.1126/science.1103773

Reports

Submitted on August 9, 2004
Accepted on January 5, 2005

The Genome of the Basidiomycetous Yeast and Human Pathogen Cryptococcus Neoformans

Brendan J. Loftus 1*, Eula Fung 2, Paola Roncaglia 3, Don Rowley 2, Paolo Amedeo 1, Dan Bruno 2, Jessica Vamathevan 4, Molly Miranda 2, Iain J. Anderson 1, James A. Fraser 5, Jonathan E. Allen 6, Ian E. Bosdet 7, Michael R. Brent 8, Readman Chiu 7, Tamara L. Doering 9, Maureen J. Donlin 10, Cletus A. D'Souza 11, Deborah S. Fox 12, Viktoriya Grinberg 4, Jianmin Fu 13, Marilyn Fukushima 2, Brian J. Haas 6, James C. Huang 5, Guilhem Janbon 14, Steven J. M. Jones 7, Hean L. Koo 6, Martin I. Krzywinski 7, June K. Kwon-Chung 15, Klaus B. Lengeler 12, Rama Maiti 6, Marco A. Marra 7, Robert E. Marra 16, Carrie A. Mathewson 7, Thomas G. Mitchell , Mihaela Pertea 6, Florenta R. Riggs 4, Steven L. Salzberg 6, Jacqueline E. Schein 7, Alla Shvartsbeyn 4, Heesun Shin 7, Martin Shumway 6, Charles A. Specht 17, Bernard B. Suh 18, Aaron Tenney 8, Terry R. Utterback 19, Brian L. Wickes 13, Jennifer R. Wortman 1, Natasja H. Wye 7, James W. Kronstad 11, Jennifer K. Lodge 10, Joseph Heitman 5, Ronald W. Davis 2, Claire M. Fraser 1, Richard W. Hyman 2

1 The Institute for Genomic Research (TIGR), 9712 Medical Center Dr., Rockville, MD 20850, USA.
2 Stanford Genome Technology Center, Stanford University, 855 California Ave., Palo Alto, CA 94304, USA.
3 Neurobiology Sector, International School for Advanced Studies (SISSA-ISAS), Via Beirut 2-4, 34014 Trieste, Italy.
4 DNA Sequencing Facility, The Institute for Genomic Research (TIGR), 9712 Medical Center Dr., Rockville, MD 20850, USA.
5 Department of Molecular Genetics and Microbiology, Duke University Medical Center, 322 CARL Building, Research Drive, Box 3546, DUMC, Durham, NC 27710, USA.
6 Bioinformatics, The Institute for Genomic Research (TIGR), 9712 Medical Center Dr., Rockville, MD 20850, USA.
7 Genome Sciences Centre, 100-570 West 7th Avenue, Vancouver, BC V5Z 4S6, Canada.
8 Laboratory for Computational Genomics, Washington University, One Brookings Drive, St. Louis, MO 63130, USA.
9 Department of Molecular Microbiology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
10 Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, 1402 S. Grand Blvd, St. Louis, MO 63104, USA.
11 The Michael Smith Laboratories, The University of British Columbia, 2185 East Mall, Vancouver, BC V6T 1Z4, Canada.
12 Department of Molecular Genetics and Microbiology, Duke University Medical Center, 322 CARL Building, Research Drive, Box 3546, DUMC, Durham, NC 27710, USA; Research Institute for Children and the Department of Pediatrics, Louisiana State Health Science Center, Children's Hospital, 200 Henry Clay Avenue, New Orleans, LA 70118, USA.
13 University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA.
14 Unité de Mycologie Moléculaire, Institut Pasteur, 25 rue du Dr. Roux, Cedex 15, Paris, France.
15 Molecular Microbiology Section, Laboratory of Clinical Investigation, National Institutes of Health (NIAID/NIH), 9000 Rockville Pike, Bethesda, MD 20892, USA.
16 Department of Molecular Genetics and Microbiology, Duke University Medical Center, 322 CARL Building, Research Drive, Box 3546, DUMC, Durham, NC 27710, USA; Plant Pathology and Ecology, The Connecticut Agricultural Experiment Station, 123 Huntington St., New Haven, CT 06511, USA.
17 Department of Medicine, Boston University, 650 Albany Street, EBRC-625 Boston, MA 02118, USA.
18 Department of Biomolecular Engineering, University of California, Santa Cruz, 1156 High St. Santa Cruz, CA 95064 USA.
19 Joint Technology Center, J. Craig Venter Foundation, 5 Research Place, Rockville, MD 20850, USA.

* To whom correspondence should be addressed.
Brendan J. Loftus , E-mail: bjloftus{at}tigr.org

Cryptococcus neoformans is a basidiomycetous yeast ubiquitous in the environment, a model for fungal pathogenesis and an opportunistic human pathogen of global importance. We have sequenced its ~20 Mb genome, which contains ~6500 intron-rich gene structures and encodes a transcriptome abundant in alternatively spliced and antisense messages. The genome is rich in transposons, many of which cluster at candidate centromeric regions. The presence of these transposons may drive karyotype instability and phenotypic variation. C. neoformans encodes unique genes that may contribute to its unusual virulence properties and comparison of two phenotypically distinct strains reveals variation in gene content in addition to sequence polymorphisms between the genomes.


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