Comparative genome hybridization reveals widespread aneuploidy in Candida albicans laboratory strains

Abstract

Clinical strains of Candida albicans are highly tolerant of aneuploidies and other genome rearrangements. We have used comparative genome hybridization (CGH), in an array format, to analyse the copy number of over 6000 open reading frames (ORFs) in the genomic DNA of C. albicans laboratory strains carrying one (CAI-4) to three (BWP17) auxotrophies. We find that during disruption of the HIS1 locus all genes telomeric to HIS1 were deleted and telomeric repeats were added to a 9 nt sequence within the transforming DNA. This deletion occurred in approximately 10% of transformants analysed and was stably maintained through two additional rounds of transformation and counterselection of the transformation marker. In one example, the deletion was repaired, apparently via break-induced replication. Furthermore, all CAI-4 strains tested were trisomic for chromosome 2 although this trisomy appears to be unstable, as it is not detected in strains subsequently derived from CAI-4. Our data indicate CGH arrays can be used to detect monosomies and trisomies, to predict the sites of chromosome breaks, and to identify chromosomal aberrations that have not been detected with other approaches in C. albicans strains. Furthermore, they highlight the high level of genome instability in C. albicans laboratory strains exposed to the stress of transformation and counterselection on 5-fluoro-orotic acid.