Abstract
Cryptococcus neoformans is a pathogenic basidiomycetous fungus that engages in outcrossing, inbreeding, and selfing forms of unisexual reproduction as well as canonical sexual reproduction between opposite mating types. Long thought to be clonal, >99% of sampled environmental and clinical isolates of C. neoformans are MATα, limiting the frequency of opposite mating-type sexual reproduction. Sexual reproduction allows eukaryotic organisms to exchange genetic information and shuffle their genomes to avoid the irreversible accumulation of deleterious changes that occur in asexual populations, known as Muller's ratchet. We tested whether unisexual reproduction, which dispenses with the requirement for an opposite mating-type partner, is able to purge the genome of deleterious mutations. We report that the unisexual cycle can restore mutant strains of C. neoformans to wild-type genotype and phenotype, including prototrophy and growth rate. Furthermore, the unisexual cycle allows attenuated strains to purge deleterious mutations and produce progeny that are returned to wild-type virulence. Our results show that unisexual populations of C. neoformans are able to avoid Muller's ratchet and loss of fitness through a unisexual reproduction cycle involving α-α cell fusion, nuclear fusion, and meiosis. Similar types of unisexual reproduction may operate in other pathogenic and saprobic eukaryotic taxa.