ArticleMolecular biology and evolution2013
A novel test for selection on cis-regulatory elements reveals positive and negative selection acting on mammalian transcriptional enhancers.
Article in Molecular biology and evolution, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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24 citing papers in PubMed, 31 citations in OpenAlex.
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- In silico genome transplants and the cis-regulatory basis of biodiversity.Trends in genetics : TIG · 2026Review
- Pleiotropy and the evolutionary stability of plastic phenotypes: a geometric framework.G3 (Bethesda, Md.) · 2026Article
- Mammalian antiviral proteins ZAP and KHNYN can independently restrict CpG-enriched avian viruses.PLoS biology · 2025Article
- Mammalian ZAP and KHNYN can independently restrict CpG-enriched avian viruses.bioRxiv : the preprint server for biology · 2025Article
- Sexual Size Dimorphism Correlates With the Number of Androgen Response Elements in Mammals, But Only in Small-Bodied Species.Genome biology and evolution · 2025Article
- Contributions of mutation and selection to regulatory variation: lessons from thePhilosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Review
- The relationship between sexual dimorphism and androgen response element proliferation in primate genomes.Evolution; international journal of organic evolution · 2022Article
- Article
- Mapping cis-regulatory elements in the midgestation mouse placenta.Scientific reports · 2021Article
- Molecular and evolutionary processes generating variation in gene expression.Nature reviews. Genetics · 2021Review
- Primary Metabolism co-Opted for Defensive Chemical Production in the Carabid Beetle, Harpalus pensylvanicus.Journal of chemical ecology · 2021Article
- Robust inference of positive selection on regulatory sequences in the human brain.Science advances · 2020Article
- The Evolution of Gene Expression in cis and trans.Trends in genetics : TIG · 2018Review
- Evolution of Brain Active Gene Promoters in Human Lineage Towards the Increased Plasticity of Gene Regulation.Molecular neurobiology · 2018Article
- Effects of mutation and selection on plasticity of a promoter activity inProceedings of the National Academy of Sciences of the United States of America · 2017Article
- Contrasting Frequencies and Effects of cis- and trans-Regulatory Mutations Affecting Gene Expression.Molecular biology and evolution · 2016Article
- Disentangling Sources of Selection on Exonic Transcriptional Enhancers.Molecular biology and evolution · 2016Article
- Which Genetics Variants in DNase-Seq Footprints Are More Likely to Alter Binding?PLoS genetics · 2016Article
- Economical analysis of saturation mutagenesis experiments.Scientific reports · 2015Article
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3 authors at 1 institution in 1 country.
Funding
Abstract
Measuring natural selection on genomic elements involved in the cis-regulation of gene expression--such as transcriptional enhancers and promoters--is critical for understanding the evolution of genomes, yet it remains a major challenge. Many studies have attempted to detect positive or negative selection in these noncoding elements by searching for those with the fastest or slowest rates of evolution, but this can be problematic. Here, we introduce a new approach to this issue, and demonstrate its utility on three mammalian transcriptional enhancers. Using results from saturation mutagenesis studies of these enhancers, we classified all possible point mutations as upregulating, downregulating, or silent, and determined which of these mutations have occurred on each branch of a phylogeny. Applying a framework analogous to Ka/Ks in protein-coding genes, we measured the strength of selection on upregulating and downregulating mutations, in specific branches as well as entire phylogenies. We discovered distinct modes of selection acting on different enhancers: although all three have experienced negative selection against downregulating mutations, the selection pressures on upregulating mutations vary. In one case, we detected positive selection for upregulation, whereas the other two had no detectable selection on upregulating mutations. Our methodology is applicable to the growing number of saturation mutagenesis data sets, and provides a detailed picture of the mode and strength of natural selection acting on cis-regulatory elements.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.