title: Microevolutionary traits and comparative population genomics of the emerging pathogenic fungus Cryptococcus gattii.
abstract: 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'.
authors.affiliation: Genome Sequencing and Analysis Program, The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA rfarrer@broadinstitute.org.|Department of Infectious Disease Epidemiology, School of Public Health, Imperial College London, London W2 1PG, UK.
authors.forename: Rhys A
authors.identifier: 0000-0001-8456-7458
authors.initials: RA
authors.lastname: Farrer
authors.affiliation: Institute of Microbiology and Infection, School of Biosciences, University of Birmingham, Birmingham B15 2TT, UK.|NIHR Surgical Reconstruction and Microbiology Research Centre, University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital Birmingham, Birmingham B15 2TH, UK.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Voelz
authors.affiliation: Department of Infectious Disease Epidemiology, School of Public Health, Imperial College London, London W2 1PG, UK.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Henk
authors.affiliation: Institute of Microbiology and Infection, School of Biosciences, University of Birmingham, Birmingham B15 2TT, UK.
authors.forename: Simon A
authors.initials: SA
authors.lastname: Johnston
authors.affiliation: Department of Infectious Disease Epidemiology, School of Public Health, Imperial College London, London W2 1PG, UK.
authors.forename: Matthew C
authors.identifier: 0000-0002-1862-6402
authors.initials: MC
authors.lastname: Fisher
authors.affiliation: Institute of Microbiology and Infection, School of Biosciences, University of Birmingham, Birmingham B15 2TT, UK.|NIHR Surgical Reconstruction and Microbiology Research Centre, University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital Birmingham, Birmingham B15 2TH, UK.
authors.forename: Robin C
authors.initials: RC
authors.lastname: May
authors.affiliation: Genome Sequencing and Analysis Program, The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
authors.forename: Christina A
authors.identifier: 0000-0002-5778-960X
authors.initials: CA
authors.lastname: Cuomo
mesh_terms: D002874:Chromosome Mapping; D003453:Cryptococcosis / Q000382:microbiology*; D056285:Cryptococcus gattii / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology*; D019143:Evolution, Molecular; D016681:Genome, Fungal; D058507:Host Specificity; D006801:Humans; D056186:Metagenomics; D010802:Phylogeny; D014774:Virulence / Q000235:genetics
keywords: Cryptococcus gattii; intracellular proliferation; microevolution; mitochondrial tubularization