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Population genomics and the evolution of virulence in the fungal pathogen Cryptococcus neoformans.

Publication ,  Journal Article
Desjardins, CA; Giamberardino, C; Sykes, SM; Yu, C-H; Tenor, JL; Chen, Y; Yang, T; Jones, AM; Sun, S; Haverkamp, MR; Heitman, J; Perfect, JR ...
Published in: Genome Res
July 2017

Cryptococcus neoformans is an opportunistic fungal pathogen that causes approximately 625,000 deaths per year from nervous system infections. Here, we leveraged a unique, genetically diverse population of C. neoformans from sub-Saharan Africa, commonly isolated from mopane trees, to determine how selective pressures in the environment coincidentally adapted C. neoformans for human virulence. Genome sequencing and phylogenetic analysis of 387 isolates, representing the global VNI and African VNB lineages, highlighted a deep, nonrecombining split in VNB (herein, VNBI and VNBII). VNBII was enriched for clinical samples relative to VNBI, while phenotypic profiling of 183 isolates demonstrated that VNBI isolates were significantly more resistant to oxidative stress and more heavily melanized than VNBII isolates. Lack of melanization in both lineages was associated with loss-of-function mutations in the BZP4 transcription factor. A genome-wide association study across all VNB isolates revealed sequence differences between clinical and environmental isolates in virulence factors and stress response genes. Inositol transporters and catabolism genes, which process sugars present in plants and the human nervous system, were identified as targets of selection in all three lineages. Further phylogenetic and population genomic analyses revealed extensive loss of genetic diversity in VNBI, suggestive of a history of population bottlenecks, along with unique evolutionary trajectories for mating type loci. These data highlight the complex evolutionary interplay between adaptation to natural environments and opportunistic infections, and that selection on specific pathways may predispose isolates to human virulence.

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Published In

Genome Res

DOI

EISSN

1549-5469

Publication Date

July 2017

Volume

27

Issue

7

Start / End Page

1207 / 1219

Location

United States

Related Subject Headings

  • Virulence Factors
  • Transcription Factors
  • Humans
  • Genome-Wide Association Study
  • Genetics, Population
  • Fungal Proteins
  • Evolution, Molecular
  • Cryptococcus neoformans
  • Cryptococcosis
  • Bioinformatics
 

Citation

APA
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Desjardins, C. A., Giamberardino, C., Sykes, S. M., Yu, C.-H., Tenor, J. L., Chen, Y., … Cuomo, C. A. (2017). Population genomics and the evolution of virulence in the fungal pathogen Cryptococcus neoformans. Genome Res, 27(7), 1207–1219. https://doi.org/10.1101/gr.218727.116
Desjardins, Christopher A., Charles Giamberardino, Sean M. Sykes, Chen-Hsin Yu, Jennifer L. Tenor, Yuan Chen, Timothy Yang, et al. “Population genomics and the evolution of virulence in the fungal pathogen Cryptococcus neoformans.Genome Res 27, no. 7 (July 2017): 1207–19. https://doi.org/10.1101/gr.218727.116.
Desjardins CA, Giamberardino C, Sykes SM, Yu C-H, Tenor JL, Chen Y, et al. Population genomics and the evolution of virulence in the fungal pathogen Cryptococcus neoformans. Genome Res. 2017 Jul;27(7):1207–19.
Desjardins, Christopher A., et al. “Population genomics and the evolution of virulence in the fungal pathogen Cryptococcus neoformans.Genome Res, vol. 27, no. 7, July 2017, pp. 1207–19. Pubmed, doi:10.1101/gr.218727.116.
Desjardins CA, Giamberardino C, Sykes SM, Yu C-H, Tenor JL, Chen Y, Yang T, Jones AM, Sun S, Haverkamp MR, Heitman J, Litvintseva AP, Perfect JR, Cuomo CA. Population genomics and the evolution of virulence in the fungal pathogen Cryptococcus neoformans. Genome Res. 2017 Jul;27(7):1207–1219.

Published In

Genome Res

DOI

EISSN

1549-5469

Publication Date

July 2017

Volume

27

Issue

7

Start / End Page

1207 / 1219

Location

United States

Related Subject Headings

  • Virulence Factors
  • Transcription Factors
  • Humans
  • Genome-Wide Association Study
  • Genetics, Population
  • Fungal Proteins
  • Evolution, Molecular
  • Cryptococcus neoformans
  • Cryptococcosis
  • Bioinformatics