Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Found 1 result for 23359205
Filters applied. Clear filters
. 2013;9(1):e1003242.
doi: 10.1371/journal.pgen.1003242. Epub 2013 Jan 24.

Gene copy-number polymorphism caused by retrotransposition in humans

Daniel R Schrider  1 , Fabio C P Navarro, Pedro A F Galante, Raphael B Parmigiani, Anamaria A Camargo, Matthew W Hahn, Sandro J de Souza
Affiliations

Gene copy-number polymorphism caused by retrotransposition in humans

Daniel R Schrider et al. PLoS Genet. 2013.

Abstract

The era of whole-genome sequencing has revealed that gene copy-number changes caused by duplication and deletion events have important evolutionary, functional, and phenotypic consequences. Recent studies have therefore focused on revealing the extent of variation in copy-number within natural populations of humans and other species. These studies have found a large number of copy-number variants (CNVs) in humans, many of which have been shown to have clinical or evolutionary importance. For the most part, these studies have failed to detect an important class of gene copy-number polymorphism: gene duplications caused by retrotransposition, which result in a new intron-less copy of the parental gene being inserted into a random location in the genome. Here we describe a computational approach leveraging next-generation sequence data to detect gene copy-number variants caused by retrotransposition (retroCNVs), and we report the first genome-wide analysis of these variants in humans. We find that retroCNVs account for a substantial fraction of gene copy-number differences between any two individuals. Moreover, we show that these variants may often result in expressed chimeric transcripts, underscoring their potential for the evolution of novel gene functions. By locating the insertion sites of these duplicates, we are able to show that retroCNVs have had an important role in recent human adaptation, and we also uncover evidence that positive selection may currently be driving multiple retroCNVs toward fixation. Together these findings imply that retroCNVs are an especially important class of polymorphism, and that future studies of copy-number variation should search for these variants in order to illuminate their potential evolutionary and functional relevance.

PubMed Disclaimer

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Detecting retroCNVs using sequence reads.
a) RetroCNVs present in the reference genome are detected by searching for retrocopies in the reference that are absent from a sequenced individual, as revealed by paired-end reads spanning the location of the retroCNV and mapping too far apart from one another. b) RetroCNVs absent from the reference genome are detected by using paired-end reads to detect retroCNV insertion sites, and c) using reads that span exon-exon junctions but do not map to the reference genome.
Figure 2
Figure 2. Estimated derived allele frequencies of retroCNVs segregating in three human subpopulations.
Allele frequencies were calculated as described in the Materials and Methods. RetroCNVs fixed in or absent from a given subpopulation are not shown.
Figure 3
Figure 3. Reduced nucleotide diversity on chromosome 18 among chromosomes containing the DHFR retroCNV in CEU.
π is shown in 10 kilobase windows for chromosomes containing the DHFR retroCNV (red) and those lacking this retroCNV (black). The location of the retroCNV insertion is marked by an arrow. While there is little difference in nucleotide diversity distal to the retroCNV, there is a recombination hotspot in that region (data from ref. [65]).
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Demuth JP, De Bie T, Stajich JE, Cristianini N, Hahn MW (2006) The evolution of mammalian gene families. PLoS ONE 1: e85 doi:10.1371/journal.pone.0000085. - DOI - PMC - PubMed
    1. Conrad DF, Pinto D, Redon R, Feuk L, Gokcumen O, et al. (2010) Origins and functional impact of copy number variation in the human genome. Nature 464: 704–712. - PMC - PubMed
    1. Dennis MY, Nuttle X, Sudmant PH, Antonacci F, Graves TA, et al. (2012) Evolution of human-specific neural SRGAP2 genes by incomplete segmental duplication. Cell 149: 912–922. - PMC - PubMed
    1. Iskow RC, Gokcumen O, Lee C (2012) Exploring the role of copy number variants in human adaptation. Trends Genet 28: 245–257. - PMC - PubMed
    1. Greenberg AJ, Moran JR, Fang S, Wu CI (2006) Adaptive loss of an old duplicated gene during incipient speciation. Mol Biol Evol 23: 401–410. - PubMed

Publication types