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Long thought to be clonal, &amp;gt;99% of sampled environmental and clinical isolates of C. neoformans are MAT\u03b1, 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\u2019s 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\u2019s ratchet and loss of fitness through a unisexual reproduction cycle involving \u03b1-\u03b1 cell fusion, nuclear fusion, and meiosis. Similar types of unisexual reproduction may operate in other pathogenic and saprobic eukaryotic taxa.<\/jats:p>","DOI":"10.1534\/genetics.114.170472","type":"journal-article","created":{"date-parts":[[2014,9,13]],"date-time":"2014-09-13T00:18:54Z","timestamp":1410567534000},"page":"1059-1069","source":"Crossref","is-referenced-by-count":26,"title":["Unisexual Reproduction Reverses Muller\u2019s Ratchet"],"prefix":"10.1093","volume":"198","author":[{"given":"Kevin C","family":"Roach","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph","family":"Heitman","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina 27710"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2014,9,11]]},"reference":[{"key":"2022011301180130400_bib1","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1126\/science.1169464","article-title":"Demonstration of genetic exchange during cyclical development of Leishmania in the sand fly vector.","volume":"324","author":"Akopyants","year":"2009","journal-title":"Science"},{"key":"2022011301180130400_bib2","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1128\/jcm.34.2.466-470.1996","article-title":"Serotyping of Cryptococcus neoformans by dot enzyme assay.","volume":"34","author":"Belay","year":"1996","journal-title":"J. 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