Inferring adaptive codon preference to understand sources of selection shaping codon usage bias

Janaina Lima De Oliveira, Atahualpa Castillo Morales, Laurence Hurst, Araxi Urrutia, Christopher R L Thompson, Jason Wolf

Research output: Contribution to journalArticlepeer-review

12 Citations (SciVal)


Alternative synonymous codons are often used at unequal frequencies. Classically, studies of such codon usage bias (CUB) attempted to separate the impact of neutral from selective forces by assuming that deviations from a predicted neutral equilibrium capture selection. However, GC-biased gene conversion (gBGC) can also cause deviation from a neutral null. Alternatively, selection has been inferred from CUB in highly expressed genes, but the accuracy of this approach has not been extensively tested, and gBGC can interfere with such extrapolations (e.g., if expression and gene conversion rates covary). It is therefore critical to examine deviations from a mutational null in a species with no gBGC. To achieve this goal, we implement such an analysis in the highly AT rich genome of Dictyostelium discoideum, where we find no evidence of gBGC. We infer neutral CUB under mutational equilibrium to quantify "adaptive codon preference,"a nontautologous genome wide quantitative measure of the relative selection strength driving CUB. We observe signatures of purifying selection consistent with selection favoring adaptive codon preference. Preferred codons are not GC rich, underscoring the independence from gBGC. Expression-associated "preference"largely matches adaptive codon preference but does not wholly capture the influence of selection shaping patterns across all genes, suggesting selective constraints associated specifically with high expression. We observe patterns consistent with effects on mRNA translation and stability shaping adaptive codon preference. Thus, our approach to quantifying adaptive codon preference provides a framework for inferring the sources of selection that shape CUB across different contexts within the genome.

Original languageEnglish
Article numbermsab099
Pages (from-to)3247-3266
Number of pages20
JournalMolecular Biology and Evolution
Issue number8
Early online date19 Apr 2021
Publication statusPublished - 31 Aug 2021

Bibliographical note

Funding Information:
This work was supported by the Biotechnology and Biological Sciences Research Council (BBSRC) (BB/M01035X/1 and BB/M007146/1 to J.B.W., L.D.H., and C.R.L.T.), the Natural Environment Research Council (NE/H020322/1 to J.B.W. and C.R.L.T. and NE/P004121/1 to AOU), a Wellcome Trust Investigator Award (WT095643AIA to C.R.L.T), a Frontier in Science CONACyT grant (682142 to AOU), a PAPPITDGAPA-UNAM grant (IA204020), and a studentship from the National Council for Scientific and Technological Development (234216/2014-0 to J.L.O). J.B.W. completed some of this work as a fellow at the Wissenschaftkolleg zu Berlin. We thank two anonymous reviewers for comments that greatly improved this work.

Publisher Copyright:
© 2021 The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.


  • biased gene conversion
  • codon usage bias
  • translation
  • weak selection

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics


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