Adenine auxotrophic heterozygosity in Candida albicans CA12

As one of the remaining enigmas in mycology, a number of natural isolates of the obligate diploid fungus Candida albicans can be induced, by UV or other mutagens, to give rise to strain-specific, recessive auxotrophic mutants at the high frequency. The puzzling phenomenon was demystified by the hypothesis of Natural heterozygosity proposed by Whelan et al (1980, Mol Gen Genet 180:107-113). According to the hypothesis, the related biosynthetic alleles of these isolates are indigenously heterozygous carrying a wild-type allele and a null allele; and the mutagenesis, rather than creates de novo mutation, instead promotes the mitotic recombination between the two non-sister chromatides resulting in the homozygosity of the null allele.;I have found that C. albicans CA12 carried adenine heterozygosity. Allele specific PCR-Southern analysis revealed that (1) CA12 is heterozygous at ADE2 carrying a wild allele and a null allele (ade2) due to a 1.3 kb deletion; (2) the adenine auxotrophic derivatives of CA12 contains ade2 allele only; while (3) C. albicans CA11, a strain that could not be induced to adenine mutant, carries ADE2 allele only. The DNA sequences of ade2 alleles from three ade2 derivatives of CA12 were identical among themselves and were identical to that from CA12, indicating that auxotrophic mutants were due to the mitotic segregation of the null ade2 allele.;After UV irradiation many of the Ade;This study demonstrated that high incidence of adenine auxotroph in CA12 was the consequence of loss of ADE2/ade2 heterozygosity and both reciprocal and non-reciprocal recombination may contribute to the process. The molecular mechanism of the ADE2 heterozygosity revealed in this study will help us to explore the evolutionary and physiological significance of the unique phenomenon.