Open Access Open Badges Research article

Impact of constitutional copy number variants on biological pathway evolution

Maria Poptsova1, Samprit Banerjee2, Omer Gokcumen3, Mark A Rubin1 and Francesca Demichelis145*

Author affiliations

1 Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY, USA

2 Department of Public Health, Weill Cornell Medical College, New York, NY, USA

3 Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, USA

4 Centre for Integrative Biology, University of Trento, Trento, Italy

5 Institute for Computational Biomedicine, Weill Cornell Medical College, New York, NY, USA

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Citation and License

BMC Evolutionary Biology 2013, 13:19  doi:10.1186/1471-2148-13-19

Published: 23 January 2013



Inherited Copy Number Variants (CNVs) can modulate the expression levels of individual genes. However, little is known about how CNVs alter biological pathways and how this varies across different populations. To trace potential evolutionary changes of well-described biological pathways, we jointly queried the genomes and the transcriptomes of a collection of individuals with Caucasian, Asian or Yoruban descent combining high-resolution array and sequencing data.


We implemented an enrichment analysis of pathways accounting for CNVs and genes sizes and detected significant enrichment not only in signal transduction and extracellular biological processes, but also in metabolism pathways. Upon the estimation of CNV population differentiation (CNVs with different polymorphism frequencies across populations), we evaluated that 22% of the pathways contain at least one gene that is proximal to a CNV (CNV-gene pair) that shows significant population differentiation. The majority of these CNV-gene pairs belong to signal transduction pathways and 6% of the CNV-gene pairs show statistical association between the copy number states and the transcript levels.


The analysis suggested possible examples of positive selection within individual populations including NF-kB, MAPK signaling pathways, and Alu/L1 retrotransposition factors. Altogether, our results suggest that constitutional CNVs may modulate subtle pathway changes through specific pathway enzymes, which may become fixed in some populations.

CNVs; Pathways; Pathway evolution; Population genetics; eQTL