Codon bias variation in Staphylococcus aureus
4 affiliations
- 1Division of Clinical Microbiology, Mayo Clinic, Rochester, Minnesota, United States of America
- 2Department of Orthopedic Surgery, Mayo Clinic, Rochester, Minnesota, United States of America
- 3Des Moines University College of Osteopathic Medicine, West Des Moines, Iowa, United States of America
- 4Division of Public Health, Infectious Diseases, and Occupational Medicine, Mayo Clinic, Rochester, Minnesota, United States of America
Abstract
Background: Staphylococcus aureus causes a multiplicity of human diseases acquired in community and healthcare settings alike around the globe. While most studies focus on coding changes to assess genome evolution and study genetic adaptation, interrogation of silent mutations in the form of synonymous codon usage bias is less well-studied. As such, understanding of patterns in codon bias at the gene and genome levels, and how codon bias impacts protein expression in S. aureus remains incomplete. Methods: The codon bias of 2,565 protein encoding genes from NCTC 8325 was queried against all publicly available closed S. aureus genomes. Using public BioSample data, genomes were sorted by disease state, submitting institution, and collection site. Codon bias was assessed at the level of gene and genome using the codon adaptation index (CAI), calculated using 30S and 50S ribosomal genes. Gene set enrichment analysis was applied to determine associations between physiological functions, CAI gene scores, and interquartile ranges. CAI scores were also compared to an in vitro S. aureus proteomics database to correlate codon bias and protein expression. Results: CAI scores varied within and between isolates at the gene and genome levels. Genes with ribosome-associated functions were most enriched among high CAI genes, and had low CAI interquartile ranges (IQR), suggesting selective pressure to maintain high expression of these genes across all S. aureus isolates. Genome sequences submitted by Aga Khan University Hospital, Nairobi, Kenya were most different from others. For the LAC USA 300 strain, CAI and protein expression were moderately positively correlated (cor = 0.534, p < 2.2e-16). Conclusions: Codon bias in S. aureus was shown to vary between gene, and to be a source of genetic variation between isolates; CAI and in vitro protein expression were positively correlated.
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BibTeX
@article{oconnor2026codon,
title = {{Codon bias variation in Staphylococcus aureus}},
author = {Kathleen O’Connor and Benjamin D. Mallinger and Nicholas A. Bedard and Robin Patel},
journal = {PLOS One},
year = {2026},
month = sep,
doi = {10.1371/journal.pone.0356997},
url = {https://doi.org/10.1371/journal.pone.0356997},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Codon bias variation in Staphylococcus aureus
AU - Kathleen O’Connor
AU - Benjamin D. Mallinger
AU - Nicholas A. Bedard
AU - Robin Patel
PY - 2026
DA - 2026/09/09
JO - PLOS One
DO - 10.1371/journal.pone.0356997
UR - https://doi.org/10.1371/journal.pone.0356997
AB - Background: Staphylococcus aureus causes a multiplicity of human diseases acquired in community and healthcare settings alike around the globe. While most studies focus on coding changes to assess genome evolution and study genetic adaptation, interrogation of silent mutations in the form of synonymous codon usage bias is less well-studied. As such, understanding of patterns in codon bias at the gene and genome levels, and how codon bias impacts protein expression in S. aureus remains incomplete. Methods: The codon bias of 2,565 protein encoding genes from NCTC 8325 was queried against all publicly available closed S. aureus genomes. Using public BioSample data, genomes were sorted by disease state, submitting institution, and collection site. Codon bias was assessed at the level of gene and genome using the codon adaptation index (CAI), calculated using 30S and 50S ribosomal genes. Gene set enrichment analysis was applied to determine associations between physiological functions, CAI gene scores, and interquartile ranges. CAI scores were also compared to an in vitro S. aureus proteomics database to correlate codon bias and protein expression. Results: CAI scores varied within and between isolates at the gene and genome levels. Genes with ribosome-associated functions were most enriched among high CAI genes, and had low CAI interquartile ranges (IQR), suggesting selective pressure to maintain high expression of these genes across all S. aureus isolates. Genome sequences submitted by Aga Khan University Hospital, Nairobi, Kenya were most different from others. For the LAC USA 300 strain, CAI and protein expression were moderately positively correlated (cor = 0.534, p < 2.2e-16). Conclusions: Codon bias in S. aureus was shown to vary between gene, and to be a source of genetic variation between isolates; CAI and in vitro protein expression were positively correlated.
SN - 1932-6203
ER -