title: Genome variation in Cryptococcus gattii, an emerging pathogen of immunocompetent hosts.
abstract: Cryptococcus gattii recently emerged as the causative agent of cryptococcosis in healthy individuals in western North America, despite previous characterization of the fungus as a pathogen in tropical or subtropical regions. As a foundation to study the genetics of virulence in this pathogen, we sequenced the genomes of a strain (WM276) representing the predominant global molecular type (VGI) and a clinical strain (R265) of the major genotype (VGIIa) causing disease in North America. We compared these C. gattii genomes with each other and with the genomes of representative strains of the two varieties of Cryptococcus neoformans that generally cause disease in immunocompromised people. Our comparisons included chromosome alignments, analysis of gene content and gene family evolution, and comparative genome hybridization (CGH). These studies revealed that the genomes of the two representative C. gattii strains (genotypes VGI and VGIIa) are colinear for the majority of chromosomes, with some minor rearrangements. However, multiortholog phylogenetic analysis and an evaluation of gene/sequence conservation support the existence of speciation within the C. gattii complex. More extensive chromosome rearrangements were observed upon comparison of the C. gattii and the C. neoformans genomes. Finally, CGH revealed considerable variation in clinical and environmental isolates as well as changes in chromosome copy numbers in C. gattii isolates displaying fluconazole heteroresistance.
authors.affiliation: The Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: C A
authors.initials: CA
authors.lastname: D'Souza
authors.forename: J W
authors.initials: JW
authors.lastname: Kronstad
authors.forename: G
authors.initials: G
authors.lastname: Taylor
authors.forename: R
authors.initials: R
authors.lastname: Warren
authors.forename: M
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authors.lastname: Yuen
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authors.initials: G
authors.lastname: Hu
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authors.initials: WH
authors.lastname: Jung
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authors.initials: A
authors.lastname: Sham
authors.forename: S E
authors.initials: SE
authors.lastname: Kidd
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authors.lastname: Tangen
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authors.lastname: Sawkins
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authors.lastname: McVicker
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authors.initials: S
authors.lastname: Shah
authors.forename: S
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authors.lastname: Gnerre
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authors.initials: A
authors.lastname: Griggs
authors.forename: Q
authors.initials: Q
authors.lastname: Zeng
authors.forename: K
authors.initials: K
authors.lastname: Bartlett
authors.forename: W
authors.initials: W
authors.lastname: Li
authors.forename: X
authors.initials: X
authors.lastname: Wang
authors.forename: J
authors.initials: J
authors.lastname: Heitman
authors.forename: J E
authors.initials: JE
authors.lastname: Stajich
authors.forename: J A
authors.initials: JA
authors.lastname: Fraser
authors.forename: W
authors.initials: W
authors.lastname: Meyer
authors.forename: D
authors.initials: D
authors.lastname: Carter
authors.forename: J
authors.initials: J
authors.lastname: Schein
authors.forename: M
authors.initials: M
authors.lastname: Krzywinski
authors.forename: K J
authors.initials: KJ
authors.lastname: Kwon-Chung
authors.forename: A
authors.initials: A
authors.lastname: Varma
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.forename: R
authors.initials: R
authors.lastname: Brunham
authors.forename: M
authors.initials: M
authors.lastname: Fyfe
authors.forename: B F F
authors.initials: BF
authors.lastname: Ouellette
authors.forename: A
authors.initials: A
authors.lastname: Siddiqui
authors.forename: M
authors.initials: M
authors.lastname: Marra
authors.forename: S
authors.initials: S
authors.lastname: Jones
authors.forename: R
authors.initials: R
authors.lastname: Holt
authors.forename: B W
authors.initials: BW
authors.lastname: Birren
authors.forename: J E
authors.initials: JE
authors.lastname: Galagan
authors.forename: C A
authors.initials: CA
authors.lastname: Cuomo
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology; D003453:Cryptococcosis / Q000276:immunology* / Q000382:microbiology*; D056285:Cryptococcus gattii / Q000145:classification / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D004196:Disease Outbreaks; D019143:Evolution, Molecular; D005260:Female; D014644:Genetic Variation; D016680:Genome, Bacterial; D005838:Genotype; D054884:Host-Pathogen Interactions; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009656:North America / Q000453:epidemiology; D010802:Phylogeny
chemical_list: D000935:Antifungal Agents