Academic journal article Genetics

Chromosome Loss Followed by Duplication Is the Major Mechanism of Spontaneous Mating-Type Locus Homozygosis in Candida Albicans

Academic journal article Genetics

Chromosome Loss Followed by Duplication Is the Major Mechanism of Spontaneous Mating-Type Locus Homozygosis in Candida Albicans

Article excerpt

ABSTRACT

Candida albicans, which is diploid, possesses a single mating-type (MTL) locus on chromosome 5, which is normally heterozygous (a/α). To mate, C. albicans must undergo MTL homozygosis to a/a or α/α. Three possible mechanisms may be used in this process, mitotic recombination, gene conversion, or loss of one chromosome 5 homolog, followed by duplication of the retained homolog. To distinguish among these mechanisms, 16 spontaneous a/a and α/α derivatives were cloned from four natural a/α strains, P37037, P37039, P75063, and P34048, grown on nutrient agar. Eighteen polymorphic (heterozygous) markers were identified on chromosome 5, 6 to the left and 12 to the right of the MTL locus. These markers were then analyzed in MTL-homozygous derivatives of the four natural a/α strains to distinguish among the three mechanisms of homozygosis. An analysis of polymorphisms on chromosomes 1, 2, and R excluded meiosis as a mechanism of MTL homozygosis. The results demonstrate that while mitotic recombination was the mechanism for homozygosis in one offspring, loss of one chromosome 5 homolog followed by duplication of the retained homolog was the mechanism in the remaining 15 offspring, indicating that the latter mechanism is the most common in the spontaneous generation of MTL homozygotes in natural strains of C. albicans in culture.

IN haploid Saccharomyces cerevisiae, mating type is regulated by a cassette system consisting of two loci, HML and HMR, which contain unexpressed copies of the MATa and 7MATa locus, respectively, and a third, MAT, which contains one expressed copy of either the MATa or TVMTa locus (HERSKOWITZ and OSHIMA 1981; HABER 1998). The MATa locus contains the mating-type gene TVMTaI, and the TVMTa locus contains the mating-type genes TWATaI and TWATa2. Mating type is dictated by the MATlocus genotype. Haploid S. cerevisiae can change its mating type by site-specific recombination at the MAT locus with a copy of the alternative silent locus (BUTLER et al. 2004). This represents a conserved system, since no mating-type information is lost when cells switch mating type. Although the yeast pathogen Candida albicans possesses mating-type genes similar to those in S. cerevisiae, C. albicans, which is diploid, possesses a single mating-type (MTL) locus situated on chromosome 5 (HULL and JOHNSON 1999), which is normally heterozygous (a/a) in natural strains (LOCKHART et al. 2002). The MTL locus of one chromosome 5 homolog contains the genes MTLaI and MTLa2, while the MTL locus on the other homolog contains the genes MTLaI and MTLa2 (HULL and JOHNSON 1999; TSONG et al. 2003). MTLa2 plays a unique role as a positive regulator of a-specific genes in C. albicans (TsONG et al. 2003). For C. albicans to express a mating type, the MTL hétérozygote must undergo homozygosis to either a/a or á/á (HULL et al. 2000; MAGEE and MAGEE 2000; LOCKHART et al. 2003). Hence, in contrast to S. cerevisiae, C. albicans loses the alternative mating-type information to be mating competent. An analysis of the MTL genotypes of a collection of 220 natural C. albicans strains revealed that ^97% were MTL heterozygous, while only 3% were MTL homozygous (LOCKHART et áú. 2002). Of the MTL-heterozygous strains, ^4% underwent spontaneous homozygosis in culture (LOCKHART et al. 2002; PUJOL et al. 2003). MTL zygosity has been shown to regulate not only mating competency, but also white-opaque switching. Cells can switch from white to opaque, a requirement for mating, only when they have undergone homozygosis (LOCKHART et al. 2002; MILLER and JOHNSON 2002). Hence, understanding how a/a cells become a/a or á/á is important not only for understanding mating, but also in understanding phenotypic switching.

C. albicans might employ three possible mechanisms to achieve homozygosis at the MTL locus. First, mitotic recombination (WHELAN and SOLL 1982) may occur between the chromosome 5 homologs at a site between the MTL locus and centromere, as depicted in Figure IA, resulting in cosegregation of two MTLa or two MTLa loci. …

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