Genome analysis reveals evolutionary mechanisms of adaptation in systemic dimorphic fungi

Dimorphic fungal pathogens cause a significant human disease burden and unlike most fungal pathogens affect immunocompetent hosts. Most dimorphic fungi are found in the family Ajellomycetaceae, including the genera Histoplasma, Blastomyces, Paracoccidioides, and the recently described Emergomyces. To examine the origin of virulence and host adaptation in these fungal pathogens, we compared the gene content of classic systemic, opportunistic, and non-pathogenic species, including new genomes for Emmonsia species and two closely non-pathogenic species, Helicocarpus griseus and Polytolypa hystricis. We examined differences in gene content between pathogens and environmental fungi, and found that gene families related to plant degradation, synthesis of secondary metabolites, and amino acid and lipid metabolism are retained in H. griseus and P. hystricis. Genes of central importance in dimorphic pathogenic fungi such as heat shock response proteins, morphological switch related proteins are conserved in non-pathogenic species. However, we found that changes in the copy number of proteases, phosphotransferases and transcription factors in systemic dimorphic relative to non-dimorphic species may have aided the evolution of specialized gene regulatory programs to rapidly adapt to higher temperatures and new nutritional environments. Notably, we found that both more basal non-pathogenic species appear homothallic, with both mating type locus idiomorphs fused at a single locus, whereas all related pathogenic species are heterothallic. These differences revealed that independent changes in nutrient acquisition capacity but similar host/substrate shift from plants to animals have occurred in the Onygenaceae and Ajellomycetaceae, and highlighted how the dimorphic pathogens from Ajellomycetaceae have adapted to the host immune response and decreased their capacity for life stages in environmental niches.