Comparative hybridization reveals extensive genome variation in the AIDS-associated pathogen Cryptococcus neoformans

Guanggan Hu^*¹ , Iris Liu^*¹ , Anita Sham¹ , Jason E Stajich²^,3 , Fred S Dietrich² and James W Kronstad¹

¹Michael Smith Laboratories, The University of British Columbia, 2185 East Mall, Vancouver, British Columbia V6T 1Z4, Canada

²Department of Molecular Genetics and Microbiology, Institute for Genome Sciences and Policy, 287 CARL Building, Duke University Medical Center, Durham, NC 27710, USA

³Department of Plant and Microbial Biology, 121 Koshland Hall, University of California, Berkeley, CA 94720-3102, USA

author email corresponding author email* Contributed equally

Genome Biology 2008, 9:R41doi:10.1186/gb-2008-9-2-r41


Published:	22 February 2008

Subject areas: Genome studies, Medicine

Abstract

Background

Genome variability can have a profound influence on the virulence of pathogenic microbes. The availability of genome sequences for two strains of the AIDS-associated fungal pathogen Cryptococcus neoformans presented an opportunity to use comparative genome hybridization (CGH) to examine genome variability between strains of different mating type, molecular subtype, and ploidy.

Results

Initially, CGH was used to compare the approximately 100 kilobase MATa and MATα mating-type regions in serotype A and D strains to establish the relationship between the Log2 ratios of hybridization signals and sequence identity. Subsequently, we compared the genomes of the environmental isolate NIH433 (MATa) and the clinical isolate NIH12 (MATα) with a tiling array of the genome of the laboratory strain JEC21 derived from these strains. In this case, CGH identified putative recombination sites and the origins of specific segments of the JEC21 genome. Similarly, CGH analysis revealed marked variability in the genomes of strains representing the VNI, VNII, and VNB molecular subtypes of the A serotype, including disomy for chromosome 13 in two strains. Additionally, CGH identified differences in chromosome content between three strains with the hybrid AD serotype and revealed that chromosome 1 from the serotype A genome is preferentially retained in all three strains.

Conclusion

The genomes of serotypes A, D, and AD strains exhibit extensive variation that spans the range from small differences (such as regions of divergence, deletion, or amplification) to the unexpected disomy for chromosome 13 in haploid strains and preferential retention of specific chromosomes in naturally occurring diploids.