scholarly journals Adaptation of the Osmotolerant Yeast Zygosaccharomyces rouxii to an Osmotic Environment Through Copy Number Amplification of FLO11D

Genetics ◽  
2013 ◽  
Vol 195 (2) ◽  
pp. 393-405 ◽  
Author(s):  
Jun Watanabe ◽  
Kenji Uehara ◽  
Yoshinobu Mogi
Keyword(s):  
Copy Number ◽  
Zygosaccharomyces Rouxii ◽  
Copy Number Amplification ◽  
Osmotolerant Yeast

scholarly journals Emergence of a Viral RNA Polymerase Variant during Gene Copy Number Amplification Promotes Rapid Evolution of Vaccinia Virus

2016 ◽  
Vol 91 (4) ◽  
Author(s):  
Kelsey R. Cone ◽  
Zev N. Kronenberg ◽  
Mark Yandell ◽  
Nels C. Elde
Keyword(s):  
Rna Polymerase ◽  
Vaccinia Virus ◽  
Copy Number ◽  
Point Mutations ◽  
Gene Copy Number ◽  
Viral Rna ◽  
Gene Copy ◽  
Trade Offs ◽  
Number Variation ◽  
Copy Number Amplification

ABSTRACT Viruses are under relentless selective pressure from host immune defenses. To study how poxviruses adapt to innate immune detection pathways, we performed serial vaccinia virus infections in primary human cells. Independent courses of experimental evolution with a recombinant strain lacking E3L revealed several high-frequency point mutations in conserved poxvirus genes, suggesting important roles for essential poxvirus proteins in innate immune subversion. Two distinct mutations were identified in the viral RNA polymerase gene A24R, which seem to act through different mechanisms to increase virus replication. Specifically, a Leu18Phe substitution encoded within A24R conferred fitness trade-offs, including increased activation of the antiviral factor protein kinase R (PKR). Intriguingly, this A24R variant underwent a drastic selective sweep during passaging, despite enhanced PKR activity. We showed that the sweep of this variant could be accelerated by the presence of copy number variation (CNV) at the K3L locus, which in multiple copies strongly reduced PKR activation. Therefore, adaptive cases of CNV can facilitate the accumulation of point mutations separate from the expanded locus. This study reveals how rapid bouts of gene copy number amplification during accrual of distant point mutations can potently facilitate poxvirus adaptation to host defenses. IMPORTANCE Viruses can evolve quickly to defeat host immune functions. For poxviruses, little is known about how multiple adaptive mutations emerge in populations at the same time. In this study, we uncovered a means of vaccinia virus adaptation involving the accumulation of distinct genetic variants within a single population. We identified adaptive point mutations in the viral RNA polymerase gene A24R and, surprisingly, found that one of these mutations activates the nucleic acid sensing factor PKR. We also found that gene copy number variation (CNV) can provide dual benefits to evolving virus populations, including evidence that CNV facilitates the accumulation of a point mutation distant from the expanded locus. Our data suggest that transient CNV can accelerate the fixation of mutations conferring modest benefits, or even fitness trade-offs, and highlight how structural variation might aid poxvirus adaptation through both direct and indirect actions.

scholarly journals Directed gene copy number amplification inPichia pastorisby vector integration into the ribosomal DNA locus

2009 ◽  
Vol 9 (8) ◽  
pp. 1260-1270 ◽  
Author(s):  
Hans Marx ◽  
Astrid Mecklenbräuker ◽  
Brigitte Gasser ◽  
Michael Sauer ◽  
Diethard Mattanovich
Keyword(s):  
Ribosomal Dna ◽  
Copy Number ◽  
Gene Copy Number ◽  
Gene Copy ◽  
Vector Integration ◽  
Copy Number Amplification

scholarly journals Classification of human cancers based on DNA copy number amplification modeling

2008 ◽  
Vol 1 (1) ◽  
Author(s):  
Samuel Myllykangas ◽  
Jarkko Tikka ◽  
Tom Böhling ◽  
Sakari Knuutila ◽  
Jaakko Hollmén
Keyword(s):  
Copy Number ◽  
Dna Copy Number ◽  
Human Cancers ◽  
Copy Number Amplification

scholarly journals Accelerated selection of a viral RNA polymerase variant during gene copy number amplification promotes rapid evolution of vaccinia virus

2016 ◽  
Author(s):  
Kelsey R. Cone ◽  
Zev N. Kronenberg ◽  
Mark Yandell ◽  
Nels C. Elde
Keyword(s):  
Rna Polymerase ◽  
Vaccinia Virus ◽  
Copy Number ◽  
Point Mutations ◽  
Gene Copy Number ◽  
Viral Rna ◽  
Gene Copy ◽  
Number Variation ◽  
Fitness Tradeoffs ◽  
Copy Number Amplification

AbstractViruses are under relentless selective pressure from host immune defenses. To study how poxviruses adapt to innate immune detection pathways, we performed serial infections of vaccinia virus in primary human cells. Independent courses of experimental evolution with a recombinant strain lacking E3L revealed several high frequency point mutations in conserved poxvirus genes, suggesting important roles for essential poxvirus proteins in innate immune subversion. Two distinct mutations were identified in the viral RNA polymerase gene A24R, which seem to act through different mechanisms to increase virus replication. Specifically, a Leu18Phe substitution in A24R conferred fitness tradeoffs, including increased activation of the antiviral factor Protein kinase R (PKR). Intriguingly, this A24R variant underwent a drastic selective sweep during passaging, despite enhanced PKR activity. We show that the sweep of this variant can be accelerated by the presence of copy number variation (CNV) at the K3L locus, which with multiple copies strongly reduces PKR activation. Therefore, adaptive cases of CNV can also facilitate the accumulation of point mutations separate from the expanded locus. This study reveals how rapid bouts of gene copy number amplification during accrual of distant point mutations can potently facilitate poxvirus adaptation to host defenses.ImportanceViruses can quickly evolve to defeat host immune functions. For poxviruses, little is known about how multiple adaptive mutations might concurrently emerge in populations. In this study, we uncovered a means of vaccinia virus adaptation involving the accumulation of distinct genetic variants within a single population. We identified adaptive point mutations in the viral RNA polymerase gene A24R, and show that these mutations can affect the activation of host nucleic acid sensing pathways through different mechanisms. We also found that structural variants within viral genomes in the form of gene copy number variation (CNV) provide dual benefits to evolving populations, including evidence that CNV facilitates the accumulation of a point mutation distant from the expanded locus. Our data suggest that transient CNV can accommodate the accumulation of mutations conferring modest benefits, or even fitness tradeoffs, and highlight how structural variation might aid poxvirus adaptation through both direct and indirect action.

scholarly journals LINC00467, Driven by Copy Number Amplification and DNA Demethylation, Is Associated with Oxidative Lipid Metabolism and Immune Infiltration in Breast Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-27
Author(s):  
Hao Bo ◽  
Wancong Zhang ◽  
Xiaoping Zhong ◽  
Jiasheng Chen ◽  
Yang Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lipid Metabolism ◽  
Network Analysis ◽  
Copy Number ◽  
Poor Prognosis ◽  
Transforming Growth Factor ◽  
Dna Demethylation ◽  
Migration And Invasion ◽  
Potential Biomarker ◽  
Copy Number Amplification

Breast cancer (BRCA) is a malignant tumor with a high incidence and poor prognosis in females. However, its pathogenesis remains unclear. In this study, based on bioinformatic analysis, we found that LINC00467 was highly expressed in BRCA and was associated with tumor metastasis and poor prognosis. The genomic and epigenetic analysis showed that LINC00467 may also be regulated by copy number amplification (CNA), chromatin openness, and DNA methylation. In vitro experiments showed that it could promote the proliferation, migration, and invasion of BRCA cells. Competitive endogenous RNA (ceRNA) regulatory network analysis and weighted gene coexpression network analysis (WGCNA) suggested that LINC00467 may play a role in signaling pathways of peroxisomal lipid metabolism, immunity, and others through microRNAs (miRNAs) targeting transforming growth factor beta 2 (TGFB2). In addition, copy number amplification and high expression of LINC00467 were associated with the low infiltration of CD8+ and CD4+ T cells. In conclusion, we found that LINC00467, driven by copy number amplification and DNA demethylation, may be a potential biomarker for the diagnosis and prognosis of BRCA and a tumor promoter acting as a potential therapeutic target for BRCA as well.

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