ArticlePLoS genetics2013
Contributions of protein-coding and regulatory change to adaptive molecular evolution in murid rodents.
Article in PLoS genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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75 citing papers in PubMed, 125 citations in OpenAlex.
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- The distribution of fitness effects of new mutations in regulatory regions of thebioRxiv : the preprint server for biology · 2026Article
- Regulatory features determine the evolutionary fate of laterally acquired genes in plants.Molecular biology and evolution · 2026Article
- Identification of alternative splicing events in cows with A1A1 and A2A2 β-casein genotypes using large gap read mapping.BMC genomics · 2025Article
- Predicting functional constraints across evolutionary timescales with phylogeny-informed genomic language models.bioRxiv : the preprint server for biology · 2025Article
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- Principles of Computation by Competitive Protein Dimerization Networks.bioRxiv : the preprint server for biology · 2024Article
- The loci of environmental adaptation in a model eukaryote.Nature communications · 2024Article
- Biases in ARG-Based Inference of Historical Population Size in Populations Experiencing Selection.Molecular biology and evolution · 2024Article
- The distribution of fitness effects during adaptive walks using a simple genetic network.PLoS genetics · 2024Article
- Shared evolutionary processes shape landscapes of genomic variation in the great apes.Genetics · 2024Article
- Shared evolutionary processes shape landscapes of genomic variation in the great apes.bioRxiv : the preprint server for biology · 2023Article
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- Population structure and inbreeding in wild house mice (Mus musculus) at different geographic scales.Heredity · 2022Article
- Insights into Mus musculus Population Structure across Eurasia Revealed by Whole-Genome Analysis.Genome biology and evolution · 2022Article
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- Molecular Evolution across Mouse Spermatogenesis.Molecular biology and evolution · 2022Article
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15 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
The contribution of regulatory versus protein change to adaptive evolution has long been controversial. In principle, the rate and strength of adaptation within functional genetic elements can be quantified on the basis of an excess of nucleotide substitutions between species compared to the neutral expectation or from effects of recent substitutions on nucleotide diversity at linked sites. Here, we infer the nature of selective forces acting in proteins, their UTRs and conserved noncoding elements (CNEs) using genome-wide patterns of diversity in wild house mice and divergence to related species. By applying an extension of the McDonald-Kreitman test, we infer that adaptive substitutions are widespread in protein-coding genes, UTRs and CNEs, and we estimate that there are at least four times as many adaptive substitutions in CNEs and UTRs as in proteins. We observe pronounced reductions in mean diversity around nonsynonymous sites (whether or not they have experienced a recent substitution). This can be explained by selection on multiple, linked CNEs and exons. We also observe substantial dips in mean diversity (after controlling for divergence) around protein-coding exons and CNEs, which can also be explained by the combined effects of many linked exons and CNEs. A model of background selection (BGS) can adequately explain the reduction in mean diversity observed around CNEs. However, BGS fails to explain the wide reductions in mean diversity surrounding exons (encompassing ~100 Kb, on average), implying that there is a substantial role for adaptation within exons or closely linked sites. The wide dips in diversity around exons, which are hard to explain by BGS, suggest that the fitness effects of adaptive amino acid substitutions could be substantially larger than substitutions in CNEs. We conclude that although there appear to be many more adaptive noncoding changes, substitutions in proteins may dominate phenotypic evolution.
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Registered trials
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.