Correlation between polyploidy and auxotrophic segregation in the imperfect yeast Candida albicans

Abstract

In order to clarify the relationship between polyploidization and the capability of phenotypic switching in the imperfect yeast Candida albicans, two types of variants were isolated as segregants from a fusant, which produced a proportion of the cell population with a higher ploidy than the rest, either in a temperaturedependent or -independent manner, when incubated at low (28°C) and high (37°C) temperatures. In the case of the temperature-dependent type of variants, high-ploidy cells appeared at 37°C but rarely at 28°C. This phenotype was named Pldts (temperature-sensitive polyploidization), and the temperature-independent phenotype was called Pld-. The appearance of high-ploidy cells in the culture of the Pldts strain at 37°C was accompanied by a significant increase in the frequency of auxotrophic variants; these variants probably occur as a result of segregation of auxotrophic markers from the heterozygous to the homozygous state. Both Pldts and Pld-phenotypes were recessive in a fusion with a Pld+ parent. An adenine auxotrophic marker (adel) was introduced into a Pldts strain in a heterozygous state, and the individual high-ploidy cells of this strain, grown at 37°C, were micromanipulated to form colonies, which consisted of red and white sectors appearing at high frequency on a pink background. When the adel auxotrophy was introduced into Pld-strains, frequently sectored colonies were produced. These results suggested an increased level of chromosome missegregation in both types of Pld mutants. Analyses by pulsed-field gel electrophoresis of Ade-segregants, derived from a micromanipulated high-ploidy cell of a Pldts strain, suggested the occurrence of nonreciprocal recombination, some of which includes chromosome loss.The dimorphic and pathogenic yeast Candida albicans is diploid as commonly isolated (17), and no sexual cycle has been observed for it (23). Diploidy seems to endow this organism with genetic stability in the short run, since a recessive mutation cannot be expressed until it exists in a homozyogous state after the occurrence of mitotic recombination. However, in the long run, the organism is postulated to accumulate recessive mutations and chromosome rearrangement. Some phenotypic variation (often called phenotypic instability or switching) has been reported to occur in this organism: Slutsky et al. (25) showed that the colony phenotype of azparticular strain, 3153A, changed at a frequency of 10-2 to 10-, which is too high to be a result of mutation. Later, the same laboratory reported a second form of colony morphology variation, smooth-opaque (4, 26). Suzuki et al. (28) albicans was assumed to be coupled to chromosomal rearrangements by Suzuki et al. (28).In this article, two types of variation (Pld-and Pldts) are shown to occur; these cause the phenotype of polyploidy in a temperature-independent or -dependent manner, respectively. Chromosome instability is shown to exist in both Pld-and Pldts strains through the demonstration of segregation of auxotrophic markers including adel. Direc...

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

“…Thus, proteins specific to these chromosomes might repress recombination at the MRS. A mutation in the SPS gene product seems to cause a loss of chromosome R (Suzuki et al, 1994) and translocation between chromosomes 4 and 7 (Iwaguchi et al, 2000). Thus, the SPS gene is a possible candidate for a regulatory element of chromosome organization.…”

Genomic Plasticity of the Human Fungal Pathogen Candida albicans

“…Such failures arise in a number of S. cerevisiae mutants (e.g., strains with defects in IPL1 and BEM2 [26] as well as in strains with defects in the RSC complex [23] and strains with defects in spindle pole body duplication [29]). Early work on C. albicans detected strains with mixed ploidy states using fluorescent microscopy (183)(184)(185). Additional work on these Sps strains, named for the inability to suppress ploidy shift changes, found that the polyploid yeast also generated increased chromosomal translocations relative to stable diploid controls (85).…”

Ploidy Variation in Fungi: Polyploidy, Aneuploidy, and Genome Evolution

“…Ploidy level heterogeneity and aneuploidy is frequently observed in clinical isolates of fungal species including C. albicans , C. neoformans , and C. glabrata (10, 11, 15, 140, 141). However, very little is known about the dynamics of ploidy changes during in vivo evolution and the effects on host-fungus interactions.…”