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Estimating the evolutionary fitness of specific synonymous codon changes
Vitor A C Pavinato1, Jody Hey1
1Department of Biology, Temple University, Philadelphia, PA 19122.
Biorxiv : the Preprint Server for Biology
|March 27, 2026
Summary
Natural selection on synonymous codons in Drosophila melanogaster is weak, with most changes showing minimal impact. This study
Area of Science:
- Evolutionary biology
- Molecular evolution
- Population genetics
Background:
- Synonymous mutations, which do not alter protein sequences, are known to be under natural selection.
- Previous studies on selection strength for synonymous mutations in Drosophila melanogaster have yielded varying results, from undetectable to strong selection.
- A new method is needed to accurately estimate selection coefficients for synonymous codon changes.
Purpose of the Study:
- To develop and apply a novel method for estimating the population selection coefficient (2Ns) for synonymous codon changes in Drosophila melanogaster.
- To investigate the strength and patterns of natural selection acting on synonymous codon usage.
- To correlate fitness estimates with other factors like codon frequencies, gene expression, and mRNA structure.
Main Methods:
- Utilized ratios of site frequency spectra (SFS) for codon changes relative to neutral changes.
- Focused solely on polymorphism data, avoiding divergence data and codon frequencies.
- Employed a selection-mutation-drift model to predict codon usage.
Main Results:
- Natural selection on synonymous codons in Drosophila melanogaster is generally weak, with |2Ns| < 2.07 for all codon pairs and |2Ns| < 1 for 64% of changes.
- Estimated codon fitness values strongly correlate with observed codon frequencies.
- The selection-mutation-drift model accurately predicts codon usage, outperforming a mutation-only model.
- Codon fitness correlates with gene expression levels and mRNA secondary structure stabilization.
Conclusions:
- Polymorphism data alone provides a clear picture of selection on synonymous codon usage, independent of divergence data.
- Natural selection, influenced by factors like gene expression and mRNA structure, plays a significant role in synonymous codon evolution.
- The validated polymorphism-based approach offers a coherent framework for understanding synonymous site evolution.
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