Loss and fragmentation of chromosome 5 are major events linked to the adaptation of rad52-ΔΔ strains of Candida albicans to sorbose

Abstract

Candida albicans can adapt and grow on sorbose plates by losing one copy of Chr5. Since rad52 mutants of Saccharomyces cerevisiae lose chromosomes at a high rate, we have investigated the ability of C. albicans rad52 to adapt to sorbose. Carad52-DeltaDelta mutants generate Sou(+) strains earlier than wild-type but the final yield is lower, probably because they die at a higher rate in sorbose. As other strains of C. albicans, CAF2 and rad52-DeltaDelta derivatives generate Sou(+) strains by a loss of one copy of Chr5 about 75% of the time. In addition, rad52 strains were able to produce Sou(+) strains by a fragmentation/deletion event in one copy of Chr5, consisting of loss of a region adjacent to the right telomere. Finally, both CAF2 and rad52-DeltaDelta produced Sou(+) strains with two apparent full copies of Chr5, suggesting that additional genomic changes may also regulate adaptation to sorbose.

Genomic Plasticity of the Human Fungal Pathogen Candida albicans

“…The Chr5 breakpoint in this strain is near 3 genes with high sequence identity, which may provide a recombination hot spot or fragile site (8). Thus, highly similar gene sequences as well as sequences resembling the natural telomere repeat appear to facilitate unintended chromosome truncations, perhaps by a mechanism similar to that used to construct strains with specific telomere-mediated chromosome truncations in S. cerevisiae (182,192) and more recently in C. albicans (6,93,174).…”

“…5D), and both breakpoints occur at the MRS. It is important to note that while Chr5 loss certainly can occur following sorbose treatment, other chromosomes are often affected as well, not all Sou ϩ strains are monosomic for Chr5 (6,17,53), and segmental trisomy of Ch4R has been observed with several Sou ϩ derivatives (E. Rustchenko, personal communication).…”

High-Frequency Genetic Contents Variations in Clinical Candida albicans Isolates

“…Aneuploidy of the entire chromosomes or large portions of chromosomes was previously largely investigated in C. albicans. 3,14,15,26) Aneuploidy was revealed in clinical isolates, [27][28][29] as well as in vitro experiments that established formation of a specific chromosome alteration in response to a specific stressful environment. 3,[30][31][32] Our analysis with GO Term Finder showed no significant enrichment of any functional category among variable genes from different isolates.…”

“…[6][7][8][9][10][11][12][13][14][15] Recently, array technology opened a new dimension in the study of genome instability. Array comparative genomic hybridization (array CGH) allows the detection of genomic variations across a whole genome.…”

“…The instability of the chromosome copy number of entire chromosomes, as well as the large portions of chromosomes was extensively studied with laboratory and freshly isolated strains using pulse-field gene electrophoresis (PFGE) as reviewed by Rustchenko, 3) Rustchenko and Sherman, 4) and Selmecki et al 5) Combined with Southern blot analysis, PFGE allowed limited analysis of gene copy number, and also could be extended to the analysis of chromosome deletions and other rearrangements. [6][7][8][9][10][11][12][13][14][15] Recently, array technology opened a new dimension in the study of genome instability. Array comparative genomic hybridization (array CGH) allows the detection of genomic variations across a whole genome.…”