Cryptococcus neoformans is a major cause of fungal meningitis, predominantly in immunocompromised individuals. This fungus has two mating types/sexes, a and α, and mating typically requires two individuals with opposite mating types.

It is mysterious why the α mating type is overwhelmingly predominant in nature and how the capacity for sexual reproduction is maintained in a largely unisexual population. We postulated that same-sex mating between α isolates may occur naturally, as it does under laboratory conditions.

By analyzing natural Cryptococcus diploid hybrid isolates containing two α alleles of different serotypic origins, this study demonstrates that same-sex mating transpires in nature. The observations that Sxi1α, a sex regulator encoded by the mating type locus, is frequently altered in C. neoformans hybrids but rarely in the haploid population, and that Sxi1α is also altered in the fertile VGIII group of the sibling species C. gattii by a different mutation support the hypothesis that these SXI1α mutations may enhance fertility, possibly in concert with other genomic changes.

αADα Hybrids Mate as α Cells. A) Hyphae produced by mating between the natural αADα hybrid 6–20 and JEC20 reference strain on V8 medium were fixed and stained with DAPI. Diploid nuclei (arrows) are brighter and larger than their haploid counterparts (arrowheads) when stained with DNA fluorescent dyes [73,97]. Dikaryotic mating hyphae containing two nuclei per compartment, which alternate position at each conjugate division, were observed during mating. Fused clamp cells are indicated by asterisks in the DIC image. (B) Basidia at different stages of development. (C) Four long spore chains produced on the surface of a basidium during mating. Scale bar, 10 μm.


The study provides insights on the genetic and environmental factors that play important roles in the evolution of the current population structure of this pathogenic fungus.

In this article published in PLoS Genetics, Xiaorong Lin and colleagues from Duke University Medical Center analyzed natural Cryptococcus diploid hybrid isolates containing two á alleles of different serotypic origins. Natural áADá hybrids that arose by fusion between two á cells of different serotypes (A and D) were identified and characterized, demonstrating that same-sex mating transpires in nature.

Same-sex mating had been observed under laboratory conditions, but direct evidence for naturally occurring same-sex mating was lacking. This study provides the first evidence of this and sheds light on the genetic and environmental factors that play important roles in the evolution of the current population structure of this pathogenic fungus.

Citation: Lin X, Litvintseva AP, Nielsen K, Patel S, Floyd A, et al. (2007) áADá hybrids of Cryptococcus neoformans: Evidence of same-sex mating in nature and hybrid fitness, PLoS Genet 3(10): e186. doi:10.1371/journal.pgen.0030186