Loss of heterozygosity, by mitotic gene conversion and crossing over, causes strain-specific adenine mutants in constitutive diploid Candida albicans

Molecular evidence is provided in this paper to elucidate a long-standing i ntriguing phenomenon in fungal genetics: that many natural isolates of the constitutive diploid organism Candida albicans yield strain-specific, reces sive mutants at a reproducible frequency that is as high as a few percent o f the surviving cells after exposure to UV irradiation or other mutagens. S outhern hybridization analysis and DNA sequence data indicated that C. albi cans CA12, a clinical isolate. is heterozygous for the ADE2 gene, carrying one functional and one null allele. Sequence analysis of the null allele re vealed the presence of a 1.3 kb deletion, which locates between two AATC re peats and spans the promoter and coding regions of the gene. The adenine au xotrophic mutants, which were readily isolated after UV irradiation of C. a lbicans CA12, were proved to be the segregants of mitotic recombination as they remained as diploid. not hemizygous or haploid. cells and were homozyg ous for ade2. Analysis of reciprocal products of the mitotic recombination detected that the process of loss of heterozygosity was mediated by mitotic crossing over (reciprocal exchange of genetic information) as well as gene conversion (nonreciprocal exchange of genetic information).