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Highly recombinant VGII Cryptococcus gattii population develops clonal outbreak clusters through both sexual

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The Cryptococcus gattii outbreak in the Pacific Northwest originated from multiple introductions and clonal expansion. Sexual reproduction played a key role in the evolution of new, virulent fungal strains.

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Area of Science:

  • Mycology
  • Genomics
  • Evolutionary Biology

Background:

  • Cryptococcus gattii caused a significant outbreak in the Pacific Northwest (PNW) starting in the late 1990s.
  • The outbreak involves three distinct clonal subpopulations: VGIIa, VGIIb, and VGIIc, with VGIIa and VGIIc unique to the PNW and showing increased virulence.

Purpose of the Study:

  • To investigate the origins and evolutionary mechanisms behind the Cryptococcus gattii outbreak in the PNW.
  • To analyze the genomic diversity of outbreak and global isolates to understand lineage emergence and adaptation.

Main Methods:

  • Whole-genome sequencing of 53 Cryptococcus gattii isolates, including PNW outbreak strains and global representatives.
  • Comparative genomic analysis to identify population structure, clonal expansion, and evidence of recombination and introgression.

Main Results:

  • Evidence of clonal expansion for VGIIa, VGIIb, and VGIIc populations in the PNW.
  • VGIIb likely originated in Australia, and VGIIa may have originated in South America, suggesting independent introductions.
  • VGIIa outbreak lineage may have evolved from a less virulent ancestor via a transient mutator phenotype (MSH2 mutation).
  • Genomic islands shared among lineages and with global isolates indicate sexual recombination, contributing to novel virulent subtypes.
  • Introgression from VGI into basal VGII isolates was identified, contributing to intra-VGII polymorphism.

Conclusions:

  • Both microevolutionary processes (e.g., mutator phenotype) and sexual reproduction are critical drivers in the emergence of infectious outbreaks from less virulent progenitors.
  • Multiple introductions and distinct evolutionary pathways, including sexual recombination and introgression, contributed to the Cryptococcus gattii PNW outbreak and the development of virulent strains.