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

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.