Genome Organization and Copy-Number Variation Reveal Clues to Virulence Evolution in <i>Coccidioides posadasii</i>
Claire A. Dubin | Mark Voorhies | Anita Sil | Marcus M. Teixeira | Bridget M. Barker | Rachel B. Brem
The human fungal pathogen <i>Coccidioides</i> spp. causes valley fever, a treatment-refractory and sometimes deadly disease prevalent in arid regions of the western hemisphere. Fungal virulence in the mammalian host hinges on a switch between growth as hyphae and as large spherules containing infectious spores. How these virulence programs are encoded in the genome remains poorly understood. Drawing on <i>Coccidioides</i> genomic resources, we first discovered a new facet of genome organization in this system: spherule-gene islands, clusters of genes physically linked in the genome that exhibited specific mRNA induction in the spherule phase. Next, we surveyed copy-number variation genome-wide among strains of <i>C. posadasii</i>. Emerging from this catalog were spherule-gene islands with striking presence–absence differentiation between <i>C. posadasii</i> populations, a pattern expected from virulence factors subjected to different selective pressures across habitats. Finally, analyzing single-nucleotide differences across <i>C. posadasii</i> strains, we identified signatures of natural selection in spherule-expressed genes. Together, our data establish spherule-gene islands as candidate determinants of virulence and targets of selection in <i>Coccidioides</i>.
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