Microevolution of Cryptococcus neoformans driven by massive tandem gene amplification

Chow, Eve W. L., Morrow, Carl A., Djordjevic, Julianne T., Wood, Ian A. and Fraser, James A. (2012) Microevolution of Cryptococcus neoformans driven by massive tandem gene amplification. Molecular Biology and Evolution, 29 8: 1987-2000. doi:10.1093/molbev/mss066

Author Chow, Eve W. L.
Morrow, Carl A.
Djordjevic, Julianne T.
Wood, Ian A.
Fraser, James A.
Title Microevolution of Cryptococcus neoformans driven by massive tandem gene amplification
Formatted title
Microevolution of Cryptococcus neoformans driven by massive tandem gene amplification
Journal name Molecular Biology and Evolution   Check publisher's open access policy
ISSN 0737-4038
Publication date 2012
Sub-type Article (original research)
DOI 10.1093/molbev/mss066
Volume 29
Issue 8
Start page 1987
End page 2000
Total pages 14
Place of publication Cary, NC, United States
Publisher Oxford University Press
Collection year 2013
Language eng
Formatted abstract
The subtelomeric regions of organisms ranging from protists to fungi undergo a much higher rate of rearrangement than is observed in the rest of the genome. While characterizing these ~40 kb regions of the human fungal pathogen Cryptococcus neoformans, we have identified a recent gene amplification event near the right telomere of chromosome 3 that involves a gene encoding an arsenite-efflux transporter (ARR3). The 3,177 bp amplicon exists in a tandem array of 2 to 15 copies, and is present exclusively in strains with the C. neoformans var. grubii subclade VNI A5 MLST profile. Strains bearing the amplification display dramatically enhanced resistance to arsenite that correlates with the copy number of the repeat; the origin of increased resistance was verified as transport-related by functional complementation of an arsenite transporter mutant of Saccharomyces cerevisiae. Subsequent experimental evolution in the presence of increasing concentrations of arsenite yielded highly resistant strains with the ARR3 amplicon further amplified to over 50 copies, accounting for up to ~1% of the whole genome and making the copy number of this repeat as high as that seen for the rDNA. The example described here therefore represents a rare evolutionary intermediate – an array that is currently in a state of dynamic flux, in dramatic contrast to relatively common, static relics of past tandem duplications that are unable to further amplify due to nucleotide divergence. Beyond identifying and engineering fungal isolates that are highly resistant to arsenite and describing the first reported instance of microevolution via massive gene amplification in C. neoformans, these results suggest that adaptation through gene
amplification may be an important mechanism that C. neoformans employs in response to environmental stresses, perhaps including those encountered during infection. More importantly, the ARR3 array will serve as an ideal model for further molecular genetic analyses of how tandem gene duplications arise and expand.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes First published online: February 14, 2012

Document type: Journal Article
Sub-type: Article (original research)
Collections: School of Mathematics and Physics
Official 2013 Collection
School of Chemistry and Molecular Biosciences
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Citation counts: TR Web of Science Citation Count  Cited 14 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 14 times in Scopus Article | Citations
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Created: Fri, 17 Feb 2012, 08:39:34 EST by Lucy O'Brien on behalf of School of Chemistry & Molecular Biosciences