Rapid mechanisms for generating genome diversity: Whole ploidy shifts, aneuploidy, and loss of heterozygosity

Human fungal pathogens can exist in a variety of ploidy states, including euploid and aneuploid forms. Ploidy change has a major impact on phenotypic properties, including the regulation of interactions with the human host. In addition, the rapid emergence of drug-resistant isolates is often associated with the formation of specific supernumerary chromosomes. Pathogens such as Candida albicans and Cryptococcus neoformans appear particularly well adapted for propagation in multiple ploidy states with novel pathways driving ploidy variation. In both species, heterozygous cells also readily undergo loss of heterozygosity (LOH), leading to additional phenotypic changes such as altered drug resistance. Here, we examine the sexual and parasexual cycles that drive ploidy variation in human fungal pathogens and discuss ploidy and LOH events with respect to their far-reaching roles in fungal adaptation and pathogenesis.