ArticlePLoS genetics2009
Evolutionary processes acting on candidate cis-regulatory regions in humans inferred from patterns of polymorphism and divergence.
Article in PLoS genetics, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers, 1 of them a synthesis that pooled it.
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Who cites it
93 citing papers in PubMed, 1 synthesis or guideline pooled it, 143 citations in OpenAlex.
- Pooled it
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- Natural Selection in Transcription Factor-DNA Interaction Motifs: A Comparative and Population Genomics Perspective.Genome biology and evolution · 2025Article
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- Long-read sequencing of 945 Han individuals identifies structural variants associated with phenotypic diversity and disease susceptibility.Nature communications · 2025Article
- The influence of gene flow on population viability in an isolated urban caracal population.Molecular ecology · 2024Article
- Selection on the promoter regions plays an important role in complex traits during duck domestication.BMC biology · 2023Article
- Using Computational Simulations to Model Deleterious Variation and Genetic Load in Natural Populations.The American naturalist · 2023Review
- A genome-wide genetic screen uncovers determinants of human pigmentation.Science (New York, N.Y.) · 2023Article
- MATS: a novel multi-ancestry transcriptome-wide association study to account for heterogeneity in the effects of cis-regulated gene expression on complex traits.Human molecular genetics · 2023Article
- Models based on best-available information support a low inbreeding load and potential for recovery in the vaquita.Heredity · 2023Article
- Genomic Underpinnings of Population Persistence in Isle Royale Moose.Molecular biology and evolution · 2023Article
- Do Noncoding and Coding Sites in Angiosperm Chloroplast DNA Have Different Mutation Processes?Genes · 2023Article
- Signature selection forces and evolutionary divergence of immune-survival genes compared between two important shrimp species.PloS one · 2023Article
- Extreme purifying selection against point mutations in the human genome.Nature communications · 2022Article
- Article
33 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Analysis of polymorphism and divergence in the non-coding portion of the human genome yields crucial information about factors driving the evolution of gene regulation. Candidate cis-regulatory regions spanning more than 15,000 genes in 15 African Americans and 20 European Americans were re-sequenced and aligned to the chimpanzee genome in order to identify potentially functional polymorphism and to characterize and quantify departures from neutral evolution. Distortions of the site frequency spectra suggest a general pattern of selective constraint on conserved non-coding sites in the flanking regions of genes (CNCs). Moreover, there is an excess of fixed differences that cannot be explained by a Gamma model of deleterious fitness effects, suggesting the presence of positive selection on CNCs. Extensions of the McDonald-Kreitman test identified candidate cis-regulatory regions with high probabilities of positive and negative selection near many known human genes, the biological characteristics of which exhibit genome-wide trends that differ from patterns observed in protein-coding regions. Notably, there is a higher probability of positive selection in candidate cis-regulatory regions near genes expressed in the fetal brain, suggesting that a larger portion of adaptive regulatory changes has occurred in genes expressed during brain development. Overall we find that natural selection has played an important role in the evolution of candidate cis-regulatory regions throughout hominid evolution.
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