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Widespread synchronization of codon usage in functionally related genes

Lopez Arcondo, J. L.; Litos, A.; Siemers, M.; Boer, M. D.; Padial, E.; Doijad, S.; Dutilh, B. E.

2025-12-12 genomics
10.64898/2025.12.10.693408 bioRxiv
Show abstract

The usage of synonymous codons varies along the genome, with strong biases in conserved and highly expressed genes that are optimized for translation. The extent of codon usage adaptation across genes and co-adaptation between genes, as well as the influence of gene function on these patterns, remain important open questions. Here, we show that codon usage is highly non-random in most bacterial genes, with at least [~]20-46% of the gene families presenting synchronized codon usage evolution. We show that co-adapting genes are co-expressed, co-regulated, metabolically connected, and functionally associated. Codon usage adaptations of key marker genes highlight differences in their expression context between microbes with alternative ecological strategies. This underappreciated regulatory dimension has important implications for function discovery and engineering.

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