Microevolutionary traits and comparative population genomics of the emerging pathogenic fungus Cryptococcus gattii

Rhys A Farrer* (Corresponding Author), Kerstin Voelz, Daniel A Henk, Simon A Johnston, Matthew C Fisher, Robin C May, Christina A Cuomo

*Corresponding author for this work

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Emerging fungal pathogens cause an expanding burden of disease across the animal kingdom, including a rise in morbidity and mortality in humans. Yet, we currently have only a limited repertoire of available therapeutic interventions. A greater understanding of the mechanisms of fungal virulence and of the emergence of hypervirulence within species is therefore needed for new treatments and mitigation efforts. For example, over the past decade, an unusual lineage of Cryptococcus gattii, which was first detected on Vancouver Island, has spread to the Canadian mainland and the Pacific Northwest infecting otherwise healthy individuals. The molecular changes that led to the development of this hypervirulent cryptococcal lineage remain unclear. To explore this, we traced the history of similar microevolutionary events that can lead to changes in host range and pathogenicity. Here, we detail fine-resolution mapping of genetic differences between two highly related Cryptococcus gattii VGIIc isolates that differ in their virulence traits (phagocytosis, vomocytosis, macrophage death, mitochondrial tubularization and intracellular proliferation). We identified a small number of single site variants within coding regions that potentially contribute to variations in virulence. We then extended our methods across multiple lineages of C. gattii to study how selection is acting on key virulence genes within different lineages.

This article is part of the themed issue 'Tackling emerging fungal threats to animal health, food security and ecosystem resilience'.

Original languageEnglish
Article number20160021
Number of pages11
JournalPhilosophical Transactions of the Royal Society B: Biological Sciences
Issue number1709
Early online date24 Oct 2016
Publication statusPublished - 5 Dec 2016

Bibliographical note

Electronic supplementary material is available
online at http://dx.doi.org/10.6084/m9.figshare.c.3493062.
Data accessibility. The genome sequence and feature files for C. gattii
R265 are available from GenBank (project accession number
All sequencing data are available from the SRA project accession
SRP017762, and along with the phenotypic data, described in
previous studies [16,24,52].

Funding. This work was financially supported by a Lister Fellowship to R.C.M., the Medical Research Council (G0601171), the Wellcome Trust (WT088148MF) and the European Research Council under the European Union’s Seventh Framework Programme (FP/2007-2013) ERC Grant agreement no. 614562. R.A.F. is supported by the Wellcome Trust. This project was supported in part by NIAID grant no. U19AI110818 to the Broad Institute. This work was also
supported by independent research funded by the National Institute of Health Research (NIHR) Surgical Reconstruction and Microbiology Research Centre. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, the NIH or the Department of Health.
Acknowledgements. We thank Arturo Casadevall for providing the 18B7
antibody used in this study and Hannah Larner for the genomic library preparation.


  • Cryptococcus gatti
  • microevolution
  • mitochondrial tubularization
  • intracellular proliferation


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