Vertebrate codon bias indicates a highly GC-rich ancestral genome
Abstract
Two factors are thought to have contributed to the origin of codon usage bias in eukaryotes: 1) genome-wide mutational forces that shape overall GC-content and create context-dependent nucleotide bias, and 2) positive selection for codons that maximize efficient and accurate translation. Particularly in vertebrates, these two explanations contradict each other and cloud the origin of codon bias in the taxon. On the one hand, mutational forces fail to explain GC-richness (~60%) of third codon positions, given the GC-poor overall genomic composition among vertebrates (~40%). On the other hand, positive selection cannot easily explain strict regularities in codon preferences. Large-scale bioinformatic assessment, of nucleotide composition of coding and non-coding sequences in vertebrates and other taxa, suggests a simple possible resolution for this contradiction. Specifically, we propose that the last common vertebrate ancestor had a GC-rich genome (~65% GC). The data suggest that whole-genome mutational bias is the major driving force for generating codon bias. As the bias becomes prominent, it begins to affect translation and can result in positive selection for optimal codons. The positive selection can, in turn, significantly modulate codon preferences.
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Optimizing GC content has a similar effect to codon optimization because GC content correlates with codon usage in vertebrates.
“Optimizing GC content has a similar effect as it correlates with codon usage in vertebrates13.”
From Algorithm for optimized mRNA design improves stability and immunogenicity (2023) · cites this paper as [13]
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Additional file 1 of Analysis of codon usage bias of WRKY transcription factors in Helianthus annuus
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- Authors
- Nabiyouni, M., Prakash, A., & Fedorov, A.
- Affiliations
- University of Toledo (US)
- Corresponding author
- Fedorov, Alexei
- ORCID
- Fedorov, Alexei
- Venue
- Gene
- Publisher
- Elsevier BV
- Published
- 2013-04
- Volume
- 519
- Issue
- 1
- Pages
- 113-119
- ISSN
- 0378-1119 (ISSN-L)
- OpenAlex
- W2086214522
- Cited by
- 25
- References
- 33
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 1 · 2023: 1 · 2022: 3 · 2021: 1 · 2018: 3 · 2017: 3 · 2016: 2 · 2015: 4 · 2014: 1
- FWCI
- 1.04
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Gene (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Science Foundation
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
- Keywords
- codon usage bias, vertebrates, GC content, mutational bias, positive selection, last common ancestor, third codon position, translation efficiency, nucleotide composition, genome evolution
- MeSH terms
- Animals, Base Composition, Chickens, Codon, Humans, Mutation, Nucleotides, Selection, Genetic, Vertebrates, Zebrafish, Gene Expression, Open Reading Frames, Genome, Evolution, Molecular, Computational Biology, Databases, Genetic
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