ArticleGenetics2011
Changes in selective effects over time facilitate turnover of enhancer sequences.
Article in Genetics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- Pervasive cryptic selection in the human noncoding genome.bioRxiv : the preprint server for biology · 2026Article
- The effect of mutational robustness on the evolvability of multicellular organisms and eukaryotic cells.Journal of evolutionary biology · 2023Article
- Phylogenetic Modeling of Regulatory Element Turnover Based on Epigenomic Data.Molecular biology and evolution · 2020Article
- Population genetic models of GERP scores suggest pervasive turnover of constrained sites across mammalian evolution.PLoS genetics · 2020Article
- Natural variation of the expression pattern of the segmentation gene even-skipped in melanogaster.Developmental biology · 2015Article
- Phylum-Level Conservation of Regulatory Information in Nematodes despite Extensive Non-coding Sequence Divergence.PLoS genetics · 2015Article
- Cis-regulatory elements and human evolution.Current opinion in genetics & development · 2014Review
- Pervasive divergence of transcriptional gene regulation in Caenorhabditis nematodes.PLoS genetics · 2014Article
- Ancestral resurrection of the Drosophila S2E enhancer reveals accessible evolutionary paths through compensatory change.Molecular biology and evolution · 2014Article
- Subtle changes in motif positioning cause tissue-specific effects on robustness of an enhancer's activity.PLoS genetics · 2014Article
- Multidimensional adaptive evolution of a feed-forward network and the illusion of compensation.Evolution; international journal of organic evolution · 2013Article
- Coevolution within and between regulatory loci can preserve promoter function despite evolutionary rate acceleration.PLoS genetics · 2012Article
- Tempo and mode in evolution of transcriptional regulation.PLoS genetics · 2012Review
- Methods to detect selection on noncoding DNA.Methods in molecular biology (Clifton, N.J.) · 2012Review
- Article
- A conserved developmental patterning network produces quantitatively different output in multiple species of Drosophila.PLoS genetics · 2011Article
- Weighing the evidence for adaptation at the molecular level.Trends in genetics : TIG · 2011Article
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Authors and funding
1 author.
Funding
Abstract
Correct gene expression is often critical and consequently stabilizing selection on expression is widespread. Yet few genes possess highly conserved regulatory DNA, and for the few enhancers that have been carefully characterized, substantial functional reorganization has often occurred. Given that natural selection removes mutations of even very small deleterious effect, how can transcription factor binding evolve so readily when it underlies a conserved phenotype? As a first step toward addressing this question, I combine a computational model for regulatory function that incorporates many aspects of our present biological knowledge with a model for the fitness effects of misexpression. I then use this model to study the evolution of enhancers. Several robust behaviors emerge: First, the selective effects of mutations at a site change dramatically over time due to substitutions elsewhere in the enhancer, and even the overall degree of constraint across the enhancer can change considerably. Second, many of the substitutions responsible for changes in binding occur at sites where previously the mutation would have been strongly deleterious, suggesting that fluctuations in selective effects at a site are important for functional turnover. Third, most substitutions contributing to the repatterning of binding and constraint are effectively neutral, highlighting the importance of genetic drift-even for enhancers underlying conserved phenotypes. These findings have important implications for phylogenetic inference of function and for interpretations of selection coefficients estimated for regulatory DNA.
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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.