Abstract

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, MATa 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 MATa allele (Aa). We previously described an unusual population of serotype A in Botswana, in which 25% of the strains contain the rare MATa 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 MATa allele (genotype AaDα) cluster with isolates of serotype A from Botswana, whereas AD hybrids that possess the MATα serotype A allele (AαDa 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) AaDα 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 MATa genome, which is otherwise geographically restricted, to survive, emigrate, and propagate throughout the world.

Highlights

  • The impact of hybridization between fungal species and varieties on their evolution is unresolved

  • We investigated whether serotype A MATa alleles in non-Botswanan AD hybrids could have originated from the VNB subpopulation of serotype A, and whether hybrid strains are fitter than strains of serotype A or serotype D

  • The high prevalence of the MATa serotype A allele among the AD hybrid strains has been puzzling because this allele is uncommon in the global population of serotype A

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Summary

Introduction

The impact of hybridization between fungal species and varieties on their evolution is unresolved. Several examples of epidemiologically successful interspecific hybrids that were able to colonize new environments and infect new hosts have been described among fungal plant pathogens [5,6,7] and oomycetes [4]. These hybrids illustrate the effect of natural hybridization on the production of biological diversity in fungal populations. Neoformans, which includes isolates of serotype D [8,9,10] These varieties represent monophyletic lineages that diverged approximately 18 million years ago [11,12], and according to the phylogenetic species concept, they may reflect cryptic species [13]. The clinical manifestations of human infections with serotype A or D appear to be similar, but experimental infections suggest that strains of serotype A are more virulent than strains of serotype D [8,15]

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