ArticlePLoS genetics2013
Strong purifying selection at synonymous sites in D. melanogaster.
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 132 papers.
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Who cites it
132 citing papers in PubMed.
- Gene-level complexity explains genome-wide variation in the distribution of fitness effects.Molecular biology and evolution · 2026Article
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- Estimating the evolutionary fitness of specific synonymous codon changes.Molecular biology and evolution · 2026Article
- From Codons to Protein Structure: Evolutionary Constraints of Mitochondrial Proteins in Corvides.Biology · 2026Article
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- Estimating the evolutionary fitness of specific synonymous codon changes.bioRxiv : the preprint server for biology · 2026Article
- Synonymous but not silent: functional codon bias reveals decoupled mitonuclear evolution in parasitic worms.Bioinformatics advances · 2026Article
- The impact of non-neutral synonymous mutations when inferring selection on nonsynonymous mutations.Genetics · 2025Article
- Evidence of long-term purging of mutation burden in killer whale Orcinus orca genomes.Heredity · 2025Article
- Functional synonymous mutations and their evolutionary consequences.Nature reviews. Genetics · 2025Review
- A Genome-Wide Analysis of Structure and Evolution in Irish and British Populations ofEvolutionary applications · 2025Article
- Testing for the Genomic Footprint of Conflict Between Life Stages in an Angiosperm and Moss Species.Genome biology and evolution · 2025Article
- Quantifying the Evolution of SNPs That Affect RNA Secondary Structure in Arabidopsis thaliana Genes.Molecular biology and evolution · 2025Article
- Codon Usage Bias: A Potential Factor Affecting VGLUT Developmental Expression and Protein Evolution.Molecular neurobiology · 2025Article
- The population chloroplast genomes of Populus reveal the phylogenetic relationship between three new taxa of sect. Leucoides and their parents.BMC genomics · 2025Article
- Dynamic Outlier Slicing Allows Broader Exploration of Adaptive Divergence: A Comparison of Individual Genome and Pool-Seq Data Linked to Humic Adaptation in Perch.Molecular ecology · 2025Article
- Applying the Classic Test dN/dS to Detect Selection in Archaea.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Fixation of Expression Divergences by Natural Selection inInternational journal of molecular sciences · 2024Article
- Genome-wide impact of codon usage bias on translation optimization in Drosophila melanogaster.Nature communications · 2024Article
- Comparative Chloroplast Genomes Analysis Provided Adaptive Evolution Insights inInternational journal of molecular sciences · 2024Article
72 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors.
Funding
Abstract
Synonymous sites are generally assumed to be subject to weak selective constraint. For this reason, they are often neglected as a possible source of important functional variation. We use site frequency spectra from deep population sequencing data to show that, contrary to this expectation, 22% of four-fold synonymous (4D) sites in Drosophila melanogaster evolve under very strong selective constraint while few, if any, appear to be under weak constraint. Linking polymorphism with divergence data, we further find that the fraction of synonymous sites exposed to strong purifying selection is higher for those positions that show slower evolution on the Drosophila phylogeny. The function underlying the inferred strong constraint appears to be separate from splicing enhancers, nucleosome positioning, and the translational optimization generating canonical codon bias. The fraction of synonymous sites under strong constraint within a gene correlates well with gene expression, particularly in the mid-late embryo, pupae, and adult developmental stages. Genes enriched in strongly constrained synonymous sites tend to be particularly functionally important and are often involved in key developmental pathways. Given that the observed widespread constraint acting on synonymous sites is likely not limited to Drosophila, the role of synonymous sites in genetic disease and adaptation should be reevaluated.
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