Genetic differences between Coccidioides spp. and closely related nonpathogenic Onygenales

Coccidioides spp. are dimorphic, pathogenic fungi that can cause severe human and animal disease. Like the other primary fungal pathogens, animal infection results in a morphologic transformation from the environmental mycelial phase to a tissue phase, known as a spherule. The sequencing and annotation of Coccidioides spp. and the genomes of several nonpathogenic Onygenales species allows comparisons that provide clues about the Coccidioides spp. genes that might be involved in pathogenesis. The analysis in this study is a gene by gene orthology comparison. Although there were few differences in the size of genes families in the Coccidioides spp.-specific group compared to the genes shared by Coccidioides spp. and nonpathogenic Onygenales, there were a number of differences in the characterization of the two types of genes. Many more Coccidioides spp.-specific genes are up-regulated expression in spherules. Coccidioides spp.-specific genes more often lacked functional annotation and were more often classified as orphan genes. Analysis by random forest machine learning confirmed that high numbers of orthologs and high levels of expression in hyphae were predictive of common genes, while high levels of expression in spherules and more nonsynonymous predicted Coccidioides spp.-specific genes. Review of individual genes in the Coccidioides spp.-specific group identified a histidine kinase, two thioredoxin genes, a calmodulin gene and ureidoglycolate hydrolase. Hopefully, identification of these genes will be useful for pursuing potential Coccidioides spp. virulence genes in the future.