Fine-Resolution Physical Mapping of Genomic Diversity in Candida albicans

Abstract

It has been suggested that Candida albicans, a diploid asexual fungus, achieves genetic diversity by genomic rearrangement. This important human pathogen may provide a system in which to analyze alternate routes to genomic diversity. C. albicans has a highly variable karyotype; its chromosomes contain a middle repeated DNA sequence called the Major Repeat Sequence (MRS), composed of subrepeats HOK, RPS, and RB2. RPS is tandemly repeated while the other subrepeats occur once in each MRS. Chromosome 7, the smallest of the eight chromosomes, has been previously mapped. The complete physical map of this chromosome was used to analyze chromosome 7 diversity in six strains, including two well-characterized laboratory strains (1006 and WO-1) and four clinical ones. We found four types of events to explain the genomic diversity: 1) Chromosome length polymorphism (CLP) results from expansion and contraction of the RPS; 2) reciprocal translocation occurs at the MRS loci; 3) chromosomal deletion; and (4) trisomy of individual chromosomes. These four phenomena play an important role in generating genomic diversity in C. albicans.

Chromosome translocation induced by the insertion of the URA blaster into the major repeat sequence (MRS) in Candida albicans

“…In most strains where chromosome translocations have been mapped, the translocation point is at an MRS (Chu et al, 1993;Navarro-Garcia et al, 1995;Iwaguchi et al, 2000Iwaguchi et al, , 2001. Chibana et al (2000) showed that several reciprocal translocations involving chromosome 7 occurred at the MRS locus. Thus, the MRS is likely to be directly involved in the process of chromosome translocation.…”

“…There are several reports of chromosome translocation involving chromosome 7 (Chu et al, 1993;Iwaguchi et al, 2000;Navarro-Garcia et al, 1995;Iwaguchi et al, 2001;Chibana et al, 2000). Both ends of the SfiI fragment 7F have been shown to be active sites for recombination, and each is flanked by major repeat sequences (MRSs).…”

Extensive chromosome rearrangements distinguish the karyotype of the hypovirulent species Candida dubliniensis from the virulent Candida albicans

“…Although large blocks of DNA, corresponding in several cases to the SfiI restriction fragments in C. albicans, are similarly organized in the two species, they are much less frequently arranged as pairs of chromosome homologues in C. dubliniensis. As in C. albicans, the MRS in C. dubliniensis seems to be a major site for chromosome reorganization (Chibana, Beckerman et al 2000) (Magee and Chibana 2002).…”

“…The origin and function of the MRS are not known, but it is found only in C. dubliniensis and C. albicans. It is the site of most of the translocations which have been mapped in C. albicans, and it is responsible for much of the chromosome length polymorphism which exists in that organism (Chibana, Beckerman et al 2000).…”

Diversity in Paracoccidioides brasiliensis . The PbGP43 gene as a genetic marker

“…The hybridization data [41] provided evidence that translocation and reciprocal translocation might contribute to chromosomal polymorphism in P. brasiliensis and that chromosomal rearrangements could provide a means for genetic variation in this organism, as proposed to occur in Candida albicans, and other fungi and eukaryotes [43][44][45]. The results on the molecular karyotypes of pathogenic fungi demonstrate the overwhelmingly fluidity of chromosome organization among eukaryotes with small genomes, which probably contributes to the maintenance of genome functionality and control of gene expression.…”