ArticleGenome research2008
Reduced purifying selection prevails over positive selection in human copy number variant evolution.
Article in Genome research, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 1 of them a synthesis that pooled it.
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Who cites it
49 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Meta-analysis of shared genetic architecture across ten pediatric autoimmune diseases.Nature medicine · 2015Pooled it
- Rapid and repeated evolution of myosin copy number in threespine stickleback.Current biology : CB · 2026Article
- Rapid and repeated evolution of myosin copy number in threespine stickleback.bioRxiv : the preprint server for biology · 2025Article
- The Domestication of Wild Boar Could Result in a Relaxed Selection for Maintaining Olfactory Capacity.Life (Basel, Switzerland) · 2024Article
- Comparative genomic diversity analysis of copy number variations (CNV) in indicine and taurine cattle thriving in Europe and Indian subcontinent.Animal biotechnology · 2023Article
- Article
- Human follicular mites: Ectoparasites becoming symbionts.Molecular biology and evolution · 2022Article
- Androgen-Binding Protein (Abp) Evolutionary History: Has Positive Selection Caused Fixation of Different Paralogs in Different Taxa of the Genus Mus?Genome biology and evolution · 2021Article
- Modelling segmental duplications in the human genome.BMC genomics · 2021Article
- Systematic identification of genetic systems associated with phenotypes in patients with rare genomic copy number variations.Human genetics · 2021Article
- Fine-Scale Characterization of Genomic Structural Variation in the Human Genome Reveals Adaptive and Biomedically Relevant Hotspots.Genome biology and evolution · 2019Article
- Analysis of Copy Number Variation in the Abp Gene Regions of Two House Mouse Subspecies Suggests Divergence during the Gene Family Expansions.Genome biology and evolution · 2017Article
- Dosage sensitivity is a major determinant of human copy number variant pathogenicity.Nature communications · 2017Article
- Copy number variants in the sheep genome detected using multiple approaches.BMC genomics · 2016Article
- CNV analysis in the Lithuanian population.BMC genetics · 2016Article
- Divergence patterns of genic copy number variation in natural populations of the house mouse (Mus musculus domesticus) reveal three conserved genes with major population-specific expansions.Genome research · 2015Article
- Copy number variation in the speciation of pigs: a possible prominent role for olfactory receptors.BMC genomics · 2015Article
- A copy number variation map of the human genome.Nature reviews. Genetics · 2015Review
- Genome-wide association study of copy number variations (CNVs) with opioid dependence.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2015Article
- Structural architecture of SNP effects on complex traits.American journal of human genetics · 2014Article
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
Copy number variation is a dominant contributor to genomic variation and may frequently underlie an individual's variable susceptibilities to disease. Here we question our previous proposition that copy number variants (CNVs) are often retained in the human population because of their adaptive benefit. We show that genic biases of CNVs are best explained, not by positive selection, but by reduced efficiency of selection in eliminating deleterious changes from the human population. Of four CNV data sets examined, three exhibit significant increases in protein evolutionary rates. These increases appear to be attributable to the frequent coincidence of CNVs with segmental duplications (SDs) that recombine infrequently. Furthermore, human orthologs of mouse genes, which, when disrupted, result in pre- or postnatal lethality, are unusually depleted in CNVs. Together, these findings support a model of reduced purifying selection (Hill-Robertson interference) within copy number variable regions that are enriched in nonessential genes, allowing both the fixation of slightly deleterious substitutions and increased drift of CNV alleles. Additionally, all four CNV sets exhibited increased rates of interspecies chromosomal rearrangement and nucleotide substitution and an increased gene density. We observe that sequences with high G+C contents are most prone to copy number variation. In particular, frequently duplicated human SD sequence, or CNVs that are large and/or observed frequently, tend to be elevated in G+C content. In contrast, SD sequences that appear fixed in the human population lie more frequently within low G+C sequence. These findings provide an overarching view of how CNVs arise and segregate in the human population.
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