The Parasexual Cycle in Candida albicans Provides an Alternative Pathway to Meiosis for the Formation of Recombinant Strains

Abstract

Candida albicans has an elaborate, yet efficient, mating system that promotes conjugation between diploid a and α strains. The product of mating is a tetraploid a/α cell that must undergo a reductional division to return to the diploid state. Despite the presence of several “meiosis-specific” genes in the C. albicans genome, a meiotic program has not been observed. Instead, tetraploid products of mating can be induced to undergo efficient, random chromosome loss, often producing strains that are diploid, or close to diploid, in ploidy. Using SNP and comparative genome hybridization arrays we have now analyzed the genotypes of products from the C. albicans parasexual cycle. We show that the parasexual cycle generates progeny strains with shuffled combinations of the eight C. albicans chromosomes. In addition, several isolates had undergone extensive genetic recombination between homologous chromosomes, including multiple gene conversion events. Progeny strains exhibited altered colony morphologies on laboratory media, demonstrating that the parasexual cycle generates phenotypic variants of C. albicans. In several fungi, including Saccharomyces cerevisiae and Schizosaccharomyces pombe, the conserved Spo11 protein is integral to meiotic recombination, where it is required for the formation of DNA double-strand breaks. We show that deletion of SPO11 prevented genetic recombination between homologous chromosomes during the C. albicans parasexual cycle. These findings suggest that at least one meiosis-specific gene has been re-programmed to mediate genetic recombination during the alternative parasexual life cycle of C. albicans. We discuss, in light of the long association of C. albicans with warm-blooded animals, the potential advantages of a parasexual cycle over a conventional sexual cycle. Candida albicans is an important human fungal pathogen that has an unconventional sexual cycle. Efficient mating requires that diploid cells of opposite mating type first switch from the more common “white” phase to the “opaque” phase and then undergo cell fusion. The resulting tetraploid strains can return to the diploid state via a non-meiotic parasexual program of concerted chromosome loss. We used SNP and comparative genome hybridization to analyze the progeny resulting from this parasexual cycle and found a range of genetically diverse strains with altered phenotypes. In addition, in a subset of these strains, genetic recombination was found to have taken place between homologous chromosomes. This recombination was dependent on Spo11, a conserved protein required for the introduction of DNA double-strand breaks in the chromosomes of eukaryotes that undergo conventional meiosis. Thus, Spo11 is required for genetic recombination and the generation of increased genetic diversity during the C. albicans parasexual cycle.