| 1 | Department of Plant and Microbial Biology, 321 Koshland Hall, University of California, Berkeley, California, 94720-3102 |
| 2 | Celera Diagnostics, Alameda, CA, USA |
| 3 | Roche Molecular Systems, Alameda, CA, USA |
| 4 | Corporación para Investigaciones Biológicas, Medellin, Colombia |
| 5 | Instituto Nacional de Salud Santafé de Bogotá, Colombia |
| 6 | Instituto de Medicina Tropical de São Paulo, Brazil |
| 7 | Instituto de Microbiologia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil |
| 8 | Center of Medical Mycology, Institute of Dermatology, Chinese Academy of Medical Sciences, Nanjing, China |
| 9 | Hospital de Enfermedades Infecciosas, Buenos Aires, Argentina |
| 10 | Microbiology Department, University of Sydney, Australia |
| 11 | Research Center for Pathogenic Fungi and Microbial Toxicoses, Chiba University, Chiba, Japan |
| 12 | 2Institute of Molecular and Cellular Biosciences, University of Tokyo, Japan |
| 13 | Departamento de Microbiología y Parasitología, Facultad de Medicina, Universidad Nacional Autónoma de México, México |
| 14 | Veterinary Resources Program, National Institutes of Health, Bethesda, MD, USA |
| 15 | Department of Medical Sciences, National Institute of Health, Nonthaburi, Thailand |
Until recently, Histoplasma capsulatum was believed to harbour three varieties, var. capsulatum (chiefly a New World human pathogen), var. duboisii (an African human pathogen) and var. farciminosum (an Old World horse pathogen), which varied in clinical manifestations and geographical distribution. We analysed the phylogenetic relationships of 137 individuals representing the three varieties from six continents using DNA sequence variation in four independent protein-coding genes. At least eight clades were idengified: (i) North American class 1 clade; (ii) North American class 2 clade; (iii) Latin American group A clade; (iv) Latin American group B clade; (v) Australian clade; (vi) Netherlands (Indonesian?) clade; (vii) Eurasian clade and (viii) African clade. Seven of eight clades represented genetically isolated groups that may be recognized as phylogenetic species. The sole exception was the Eurasian clade which originated from within the Latin American group A clade. The phylogenetic relationships among the clades made a star phylogeny. Histoplasma capsulatum var. capsulatum individuals were found in all eight clades. The African clade included all of the H. capsulatum var. duboisii individuals as well as individuals of the other two varieties. The 13 individuals of var. farciminosum were distributed among three phylogenetic species. These findings suggest that the three varieties of Histoplasma are phylogenetically meaningless. Instead we have to recognize the existence of genetically distinct geographical populations or phylogenetic species. Combining DNA substitution rates of protein-coding genes with the phylogeny suggests that the radiation of Histoplasma started between 3 and 13 million years ago in Latin America.