ArticleGenome biology2005
Evidence for selection on synonymous mutations affecting stability of mRNA secondary structure in mammals.
Article in Genome biology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 188 papers, 2 of them syntheses that pooled it.
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Who cites it
188 citing papers in PubMed, 2 syntheses or guidelines pooled it, 348 citations in OpenAlex.
- Body mass index stratified meta-analysis of genome-wide association studies of polycystic ovary syndrome in women of European ancestry.BMC genomics · 2024Pooled it
- Associations of the 5-hydroxytryptamine (serotonin) receptor 1B gene (HTR1B) with alcohol, cocaine, and heroin abuse.American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics · 2013Pooled it
- A novel synonymous TSC2 mutation in a Chinese family leads to tuberous sclerosis type 2 by disrupting Normal pre-mRNA splicing.Journal, genetic engineering & biotechnology · 2026Article
- Folding the message: mRNA structure as a regulatory layer of human mitochondrial gene expression.Biochimica et biophysica acta. Molecular cell research · 2026Review
- Synonymous mutations in essential genes infrequently produce fitness effects in human cell lines.Nucleic acids research · 2026Article
- Positive selection on brain cis-regulatory elements in the human lineage drives changes in gene expression and susceptibility to neuropsychiatric disorders.HGG advances · 2026Article
- Holostean genomes reveal evolutionary novelty in the vertebrate immunoproteasome that have implications for MHCI function.Molecular biology and evolution · 2026Article
- The mutation landscape of Daphnia obtusa reveals evolutionary forces shaping genome stability.Molecular biology and evolution · 2026Article
- Recent Insights Into the Evolutionary Genomics of the Critically Endangered Aye-Aye (Daubentonia madagascariensis).American journal of primatology · 2025Review
- Bacterial gene 5' ends have unusual mutation rates that can mislead tests of selection.PLoS biology · 2025Article
- The mutation landscape ofbioRxiv : the preprint server for biology · 2025Article
- ECSFinder: optimized prediction of evolutionarily conserved RNA secondary structures from genome sequences.Nucleic acids research · 2025Article
- Quantifying the Evolution of SNPs That Affect RNA Secondary Structure in Arabidopsis thaliana Genes.Molecular biology and evolution · 2025Article
- RNA editing generates mRNA isoforms with distinct stabilities that may expand the thermal tolerance of mRNA and proteins inZoological research · 2025Article
- Interpreting mammalian synonymous site conservation in light of the unwanted transcript hypothesis.Nature communications · 2025Article
- DiMA: sequence diversity dynamics analyser for viruses.Briefings in bioinformatics · 2024Article
- Compositional Features and Codon Usage Pattern of Genes Associated with Parkinson's Disease.Molecular neurobiology · 2024Article
- Selection on synonymous sites: the unwanted transcript hypothesis.Nature reviews. Genetics · 2024Review
- Fitness benefits of a synonymous substitution in an ancient EF-Tu gene depend on the genetic background.Journal of bacteriology · 2024Article
- Commonalities and differences in the mutational signature and somatic driver mutation landscape across solid and hollow viscus organs.Oncogene · 2023Review
128 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
backgroundIn mammals, contrary to what is usually assumed, recent evidence suggests that synonymous mutations may not be selectively neutral. This position has proven contentious, not least because of the absence of a viable mechanism. Here we test whether synonymous mutations might be under selection owing to their effects on the thermodynamic stability of mRNA, mediated by changes in secondary structure.
resultsWe provide numerous lines of evidence that are all consistent with the above hypothesis. Most notably, by simulating evolution and reallocating the substitutions observed in the mouse lineage, we show that the location of synonymous mutations is non-random with respect to stability. Importantly, the preference for cytosine at 4-fold degenerate sites, diagnostic of selection, can be explained by its effect on mRNA stability. Likewise, by interchanging synonymous codons, we find naturally occurring mRNAs to be more stable than simulant transcripts. Housekeeping genes, whose proteins are under strong purifying selection, are also under the greatest pressure to maintain stability.
conclusionTaken together, our results provide evidence that, in mammals, synonymous sites do not evolve neutrally, at least in part owing to selection on mRNA stability. This has implications for the application of synonymous divergence in estimating the mutation rate.
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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.