Mitotic Recombination and Adaptive Genomic Changes in Human Pathogenic Fungi.

Journal Article (Journal Article;Review)

Genome rearrangements and ploidy alterations are important for adaptive change in the pathogenic fungal species Candida and Cryptococcus, which propagate primarily through clonal, asexual reproduction. These changes can occur during mitotic growth and lead to enhanced virulence, drug resistance, and persistence in chronic infections. Examples of microevolution during the course of infection were described in both human infections and mouse models. Recent discoveries defining the role of sexual, parasexual, and unisexual cycles in the evolution of these pathogenic fungi further expanded our understanding of the diversity found in and between species. During mitotic growth, damage to DNA in the form of double-strand breaks (DSBs) is repaired, and genome integrity is restored by the homologous recombination and non-homologous end-joining pathways. In addition to faithful repair, these pathways can introduce minor sequence alterations at the break site or lead to more extensive genetic alterations that include loss of heterozygosity, inversions, duplications, deletions, and translocations. In particular, the prevalence of repetitive sequences in fungal genomes provides opportunities for structural rearrangements to be generated by non-allelic (ectopic) recombination. In this review, we describe DSB repair mechanisms and the types of resulting genome alterations that were documented in the model yeast Saccharomyces cerevisiae. The relevance of similar recombination events to stress- and drug-related adaptations and in generating species diversity are discussed for the human fungal pathogens Candida albicans and Cryptococcus neoformans.

Full Text

Duke Authors

Cited Authors

  • Gusa, A; Jinks-Robertson, S

Published Date

  • November 7, 2019

Published In

Volume / Issue

  • 10 / 11

PubMed ID

  • 31703352

Pubmed Central ID

  • PMC6895784

Electronic International Standard Serial Number (EISSN)

  • 2073-4425

Digital Object Identifier (DOI)

  • 10.3390/genes10110901


  • eng

Conference Location

  • Switzerland