Gene Network Polymorphism Illuminates Loss and Retention of Novel RNAi Silencing Components in the Cryptococcus Pathogenic Species Complex.
Abstract
RNAi is a ubiquitous pathway that serves central functions throughout eukaryotes,
including maintenance of genome stability and repression of transposon expression
and movement. However, a number of organisms have lost their RNAi pathways, including
the model yeast Saccharomyces cerevisiae, the maize pathogen Ustilago maydis, the
human pathogen Cryptococcus deuterogattii, and some human parasite pathogens, suggesting
there may be adaptive benefits associated with both retention and loss of RNAi. By
comparing the RNAi-deficient genome of the Pacific Northwest Outbreak C. deuterogattii
strain R265 with the RNAi-proficient genomes of the Cryptococcus pathogenic species
complex, we identified a set of conserved genes that were lost in R265 and all other
C. deuterogattii isolates examined. Genetic and molecular analyses reveal several
of these lost genes play roles in RNAi pathways. Four novel components were examined
further. Znf3 (a zinc finger protein) and Qip1 (a homolog of N. crassa Qip) were found
to be essential for RNAi, while Cpr2 (a constitutive pheromone receptor) and Fzc28
(a transcription factor) are involved in sex-induced but not mitosis-induced silencing.
Our results demonstrate that the mitotic and sex-induced RNAi pathways rely on the
same core components, but sex-induced silencing may be a more specific, highly induced
variant that involves additional specialized or regulatory components. Our studies
further illustrate how gene network polymorphisms involving known components of key
cellular pathways can inform identification of novel elements and suggest that RNAi
loss may have been a core event in the speciation of C. deuterogattii and possibly
contributed to its pathogenic trajectory.
Type
Journal articleSubject
CryptococcusFungal Proteins
Gene Regulatory Networks
Genome, Fungal
Humans
Polymorphism, Genetic
RNA Interference
Signal Transduction
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https://hdl.handle.net/10161/11693Published Version (Please cite this version)
10.1371/journal.pgen.1005868Publication Info
Feretzaki, M; Billmyre, RB; Clancey, SA; Wang, X; & Heitman, J (2016). Gene Network Polymorphism Illuminates Loss and Retention of Novel RNAi Silencing Components
in the Cryptococcus Pathogenic Species Complex. PLoS Genet, 12(3). pp. e1005868. 10.1371/journal.pgen.1005868. Retrieved from https://hdl.handle.net/10161/11693.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Joseph Heitman
Chair, Department of Molecular Genetics and Microbiology
Joseph Heitman was an undergraduate at the University of Chicago (1980-1984), graduating
from the BS-MS program with dual degrees in chemistry and biochemistry with general
and special honors. He then matriculated as an MD-PhD student at Cornell and Rockefeller
Universities and worked with Peter Model and Norton Zinder on how restriction enzymes
recognize specific DNA sequences and how bacteria respond to and repair DNA breaks
and nicks. Dr. Heitman moved as an EMBO long-term fellow to the Bi

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