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Interspecific and intervarietal hybridization may contribute to the biological diversity of fungal populations.  Cryptococcus neoformans  is a pathogenic yeast and the most common fungal cause of meningitis in patients with AIDS. Most patients are infected with either of the two varieties of  C. neoformans,  designated as serotype A  (C. neoformans  var.  grubii)  or serotype D  (C. neoformans  var.  neoformans) . In addition, serotype AD strains, which are hybrids of these two varieties, are commonly isolated from clinical and environmental samples. While most isolates of serotype A and serotype D are haploid, AD strains are diploid or aneuploid, and contain two sets of chromosomes and two mating type alleles,  MAT a   and  MATα,  one from each of the serotypes. The global population of serotype A is dominated by isolates with the  MATα  mating type (Aα); however, about half of the globally analyzed AD strains possess the extremely rare serotype A  MAT a   allele (A a ). We previously described an unusual population of serotype A in Botswana, in which 25% of the strains contain the rare  MAT a   allele. Here we utilized two methods, phylogenetic analysis of three genes and genotyping by scoring amplified fragment length polymorphisms, and discovered that AD hybrid strains possessing the rare serotype A  MAT a   allele (genotype A a Dα) cluster with isolates of serotype A from Botswana, whereas AD hybrids that possess the  MAT α serotype A allele (AαD a  and AαDα) cluster with cosmopolitan isolates of serotype A. We also determined that AD hybrid strains are more resistant to UV irradiation than haploid serotype A strains from Botswana. These findings support two hypotheses: (i) A a Dα strains originated in sub-Saharan Africa from a cross between strains of serotypes A and D; and (ii) this fusion produced hybrid strains with increased fitness, enabling the Botswanan serotype A  MAT a   genome, which is otherwise geographically restricted, to survive, emigrate, and propagate throughout the world.

Many Globally Isolated AD Hybrid Strains of Cryptococcus neoformans Originated in Africa