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Within these two recognized species, phylogenetic analysis reveals at least six cryptic species defined as molecular types (VNI\/II\/B, VNIV, VGI, VGII, VGIII, and VGIV) that comprise the pathogenic<jats:italic>Cryptococcus<\/jats:italic>species complex. These pathogenic species are clustered in the<jats:italic>Filobasidiella<\/jats:italic>clade within the order Tremellales. Previous studies have shown that the<jats:italic>Filobasidiella<\/jats:italic>clade also includes several saprobic fungi isolated from insect frass, but information evaluating the relatedness of the saprobes and pathogens within this cluster is limited. Here, the phylogeny encompassing a subset of species in the Tremellales lineage that clusters closely with the pathogenic<jats:italic>Cryptococcus<\/jats:italic>species complex was resolved by employing a multilocus sequencing approach for phylogenetic analysis. Six highly conserved genomic loci from 15 related basidiomycete species were sequenced, and the alignments from the concatenated gene sequences were evaluated with different tree-building criteria. Furthermore, these 15 species were subjected to virulence and phenotype assays to evaluate their pathogenic potential. These studies revealed that<jats:italic>Cryptococcus amylolentus<\/jats:italic>and<jats:italic>Tsuchiyaea wingfieldii<\/jats:italic>, two nonpathogenic sibling species, are the taxa most closely related to the pathogens<jats:italic>C. neoformans<\/jats:italic>and<jats:italic>C. gattii<\/jats:italic>and together with<jats:italic>Filobasidiella depauperata<\/jats:italic>form a<jats:italic>Cryptococcus<\/jats:italic>sensu stricto group. Five other saprobic yeast species form the<jats:italic>Kwoniella<\/jats:italic>clade, which appears to be a part of a more distantly related sensu lato group. This study establishes a foundation for future comparative genomic approaches that will provide insight into the structure, function, and evolution of the mating type locus, the transitions in modes of sexual reproduction, and the emergence of human pathogenic species from related or ancestral saprobic species.<\/jats:p>","DOI":"10.1128\/ec.00373-08","type":"journal-article","created":{"date-parts":[[2009,1,17]],"date-time":"2009-01-17T03:01:56Z","timestamp":1232161316000},"page":"353-361","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":96,"title":["Phylogeny and Phenotypic Characterization of Pathogenic<i>Cryptococcus<\/i>Species and Closely Related Saprobic Taxa in the Tremellales"],"prefix":"10.1128","volume":"8","author":[{"given":"Keisha","family":"Findley","sequence":"first","affiliation":[{"name":"Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina 27710"}]},{"given":"Marianela","family":"Rodriguez-Carres","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina 27710"}]},{"given":"Banu","family":"Metin","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina 27710"}]},{"given":"Johannes","family":"Kroiss","sequence":"additional","affiliation":[{"name":"Department of Zoology, University of Regensburg, 93040 Regensburg, Germany"}]},{"given":"A\u0301lvaro","family":"Fonseca","sequence":"additional","affiliation":[{"name":"Centro de Recursos Microbiolo\u0301gicos, Departamento de Cie\u0302ncias da Vida, Faculdade de Cie\u0302ncias e Tecnologia, Universidade Nova de Lisboa, 2829-516 Caparica, Portugal"}]},{"given":"Rytas","family":"Vilgalys","sequence":"additional","affiliation":[{"name":"Department of Biology, Duke University, Durham, North Carolina 27708"}]},{"given":"Joseph","family":"Heitman","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina 27710"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2836(05)80360-2"},{"key":"e_1_3_2_3_2","first-page":"13","volume":"38","year":"1995","unstructured":"Bandoni, R. 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