We aim to study the evolutionary biology of Paracoccidioides brasiliensis, the ascomycete fungus that causes paracoccidioidomycosis, the most important endemic mycosis in South America. Ours is a collaboration between Colombian medical mycologists with clinical and research experience with P. brasiliensis and a US mycologist experienced with fungal evolutionary biology. We have three specific aims: (1) Is P. brasiliensis one species or more than one? (2) Does P. brasiliensis reproduce clonally or by recombination? (3) Are clinical isolates of P. brasiliensis representative of environmental isolates, or are only some environmental genotypes capable of infecting humans? The importance and approach for each aim follow. (1) Fungal species concepts are morphological, but our experience with Histoplasma capsulatum, Coccidioides immitis and Aspergillus flavus shows that a morphological species can harbor more than one genetically isolated species. These species may have different phenotypes, including pathogenicity, so physicians must know the species. We will use the same strategy that we developed with C. immitis, A. flavus and H. capsulatum to use the interface of congruence and incongruity of four or five gene genealogies to define genetically isolated species. (2) P. brasiliensis is thought to reproduce clonally, which means that the same pathogenic genotype may be encountered repeatedly and that any variable DNA region could be used to track strains. However, our experience with C. immitis and A. flavus is that asexual fungi can also recombine; causing different patients to be infected with genetically different pathogens which cannot be tracked with just one gene. The same data used to assess species can be used to determine reproductive mode, again by gene genealogy congruence within species. (3) If genotypes of clinical isolates are not representative of all environmental isolates, it is possible that comparison of the genomes of the two types of isolates may help find genes responsible for pathogenicity. Finding pathogenicity genes is one of the goals of the field of medical mycology and comparing pools of DNA from pathogens and nonpathogens could solve the problem.
