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Genome-wide analysis of heat stress-stimulated transposon mobility in the human fungal pathogen Cryptococcus deneoformans.

Publication ,  Journal Article
Gusa, A; Yadav, V; Roth, C; Williams, JD; Shouse, EM; Magwene, P; Heitman, J; Jinks-Robertson, S
Published in: Proc Natl Acad Sci U S A
January 24, 2023

We recently reported transposon mutagenesis as a significant driver of spontaneous mutations in the human fungal pathogen Cryptococcus deneoformans during murine infection. Mutations caused by transposable element (TE) insertion into reporter genes were dramatically elevated at high temperatures (37° vs. 30°) in vitro, suggesting that heat stress stimulates TE mobility in the Cryptococcus genome. To explore the genome-wide impact of TE mobilization, we generated transposon accumulation lines by in vitro passage of C. deneoformans strain XL280α for multiple generations at both 30° and at the host-relevant temperature of 37°. Utilizing whole-genome sequencing, we identified native TE copies and mapped multiple de novo TE insertions in these lines. Movements of the T1 DNA transposon occurred at both temperatures with a strong bias for insertion between gene-coding regions. By contrast, the Tcn12 retrotransposon integrated primarily within genes and movement occurred exclusively at 37°. In addition, we observed a dramatic amplification in copy number of the Cnl1 (Cryptococcus neoformans LINE-1) retrotransposon in subtelomeric regions under heat-stress conditions. Comparing TE mutations to other sequence variations detected in passaged lines, the increase in genomic changes at elevated temperatures was primarily due to mobilization of the retroelements Tcn12 and Cnl1. Finally, we found multiple TE movements (T1, Tcn12, and Cnl1) in the genomes of single C. deneoformans isolates recovered from infected mice, providing evidence that mobile elements are likely to facilitate microevolution and rapid adaptation during infection.

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Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

January 24, 2023

Volume

120

Issue

4

Start / End Page

e2209831120

Location

United States

Related Subject Headings

  • Retroelements
  • Mice
  • Humans
  • Heat-Shock Response
  • Genome
  • DNA Transposable Elements
  • Cryptococcus neoformans
  • Cryptococcosis
  • Animals
 

Citation

APA
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ICMJE
MLA
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Gusa, A., Yadav, V., Roth, C., Williams, J. D., Shouse, E. M., Magwene, P., … Jinks-Robertson, S. (2023). Genome-wide analysis of heat stress-stimulated transposon mobility in the human fungal pathogen Cryptococcus deneoformans. Proc Natl Acad Sci U S A, 120(4), e2209831120. https://doi.org/10.1073/pnas.2209831120
Gusa, Asiya, Vikas Yadav, Cullen Roth, Jonathan D. Williams, Eva Mei Shouse, Paul Magwene, Joseph Heitman, and Sue Jinks-Robertson. “Genome-wide analysis of heat stress-stimulated transposon mobility in the human fungal pathogen Cryptococcus deneoformans.Proc Natl Acad Sci U S A 120, no. 4 (January 24, 2023): e2209831120. https://doi.org/10.1073/pnas.2209831120.
Gusa A, Yadav V, Roth C, Williams JD, Shouse EM, Magwene P, et al. Genome-wide analysis of heat stress-stimulated transposon mobility in the human fungal pathogen Cryptococcus deneoformans. Proc Natl Acad Sci U S A. 2023 Jan 24;120(4):e2209831120.
Gusa, Asiya, et al. “Genome-wide analysis of heat stress-stimulated transposon mobility in the human fungal pathogen Cryptococcus deneoformans.Proc Natl Acad Sci U S A, vol. 120, no. 4, Jan. 2023, p. e2209831120. Pubmed, doi:10.1073/pnas.2209831120.
Gusa A, Yadav V, Roth C, Williams JD, Shouse EM, Magwene P, Heitman J, Jinks-Robertson S. Genome-wide analysis of heat stress-stimulated transposon mobility in the human fungal pathogen Cryptococcus deneoformans. Proc Natl Acad Sci U S A. 2023 Jan 24;120(4):e2209831120.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

January 24, 2023

Volume

120

Issue

4

Start / End Page

e2209831120

Location

United States

Related Subject Headings

  • Retroelements
  • Mice
  • Humans
  • Heat-Shock Response
  • Genome
  • DNA Transposable Elements
  • Cryptococcus neoformans
  • Cryptococcosis
  • Animals