Authors
Vitor A C Pavinato, Jody Hey
Published in
Molecular biology and evolution. Aug 11, 2026. Epub Aug 11, 2026.
Abstract
Synonymous mutations do not alter proteins but undergo natural selection in many species. For Drosophila melanogaster, reports on selection strength vary from undetectable to surprisingly strong. Here we apply a new method to estimate the population selection coefficient (2Ns) for all 134 ordered pairs of synonymous codon changes. The method uses ratios of site frequency spectra for synonymous codon changes and matched neutral changes, avoiding reliance on divergence data or codon frequencies and remaining relatively insensitive to demographic history. Results indicate that natural selection on synonymous codons is weak, with |2Ns| < 2.30 for all pairs of codons and |2Ns| < 1 for 49% of codon changes. Despite being derived solely from polymorphism data, codon fitness estimates are strongly correlated with observed codon frequencies. A selection-mutation-drift model based on these estimates accurately predicts codon usage, while a model based on mutation alone fails. Codon fitness estimates also predict expression-associated codon usage, with higher-fitness codons used more often in highly expressed genes. However, the effect of expression on selection strength is modest, with a 10-fold increase in expression predicted to increase the average strength of selection on synonymous codons by only 14%. Finally, we detect clear signs that selection favors codon changes that stabilize mRNA secondary structure. The convergence of multiple independent lines of evidence validates this polymorphism-based approach and provides a coherent framework for understanding selection on synonymous site evolution.
PMID:
42578945
Bibliographic data and abstract were imported from PubMed on 11 Aug 2026.
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