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Updated: Jul 11, 2025

Detection of Copy Number Alterations Using Single Cell Sequencing
Published on: February 17, 2017
Multilevel gene expression changes in lineages containing adaptive copy number variants.
Pieter Spealman1, Carolina de Santana2, Titir De1
1Center for Genomics and Systems Biology, Department of Biology, New York University.
Adaptive copy-number variants (CNVs) in yeast evolved under nutrient limitation. CNVs impact gene expression across RNA, translation, and protein levels, revealing complex regulatory changes during adaptation.
Area of Science:
- Evolutionary biology
- Genetics
- Molecular biology
Background:
- Copy-number variants (CNVs) are key drivers of adaptive evolution.
- CNVs can confer fitness advantages but may also impose costs.
- Recurrent CNV evolution at the GAP1 locus was observed in yeast under glutamine limitation.
Purpose of the Study:
- To investigate the role of gene expression in adaptation mediated by CNVs.
- To understand how CNVs affect gene expression at multiple regulatory levels (transcriptome, translatome, proteome).
- To identify regulatory mechanisms influenced by adaptive CNVs.
Main Methods:
- Evolution experiments with Saccharomyces cerevisiae in glutamine-limited chemostats.
- Measurement of transcriptome, translatome, and proteome in evolved yeast strains with unique CNVs.
- Analysis of gene expression efficiency at RNA, translation, and protein levels.
Main Results:
- CNV amplification positively correlated with RNA abundance, but this effect diminished at the proteome level (post-transcriptional dosage compensation).
- Widespread divergence in gene expression efficiency was observed across regulatory steps.
- Genes with altered translational efficiency were enriched for regulatory elements like upstream open reading frames and RNA binding sites.
Conclusions:
- Adaptive CNVs induce significant changes in gene expression at multiple regulatory levels.
- Post-transcriptional mechanisms play a role in buffering the effects of CNV amplification.
- Evolutionary adaptation involving CNVs involves complex alterations in gene expression regulation.
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