tRNA properties help shape codon pair preferences in open reading frames
Open accessAbstract
Translation elongation is an accurate and rapid process, dependent upon efficient juxtaposition of tRNAs in the ribosomal A- and P-sites. Here, we sought evidence of A- and P-site tRNA interaction by examining bias in codon pair choice within open reading frames from a range of genomes. Three distinct and marked effects were revealed once codon and dipeptide biases had been subtracted. First, in the majority of genomes, codon pair preference is primarily determined by a tetranucleotide combination of the third nucleotide of the P-site codon, and all 3 nt of the A-site codon. Second, pairs of rare codons are generally under-used in eukaryotes, but over-used in prokaryotes. Third, the analysis revealed a highly significant effect of tRNA-mediated selection on codon pairing in unicellular eukaryotes, Bacillus subtilis, and the gamma proteobacteria. This was evident because in these organisms, synonymous codons decoded in the A-site by the same tRNA exhibit significantly similar P-site pairing preferences. Codon pair preference is thus influenced by the identity of A-site tRNAs, in combination with the P-site codon third nucleotide. Multivariate analysis identified conserved nucleotide positions within A-site tRNA sequences that modulate codon pair preferences. Structural features that regulate tRNA geometry within the ribosome may govern genomic codon pair patterns, driving enhanced translational fidelity and/or rate.
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The main selective effects on codon context are found in the nucleotides following the codon in the 3' direction.
“The main selective effects on codon context are found in the nucleotides following the codon in the 3' direction [16,18,19,22].”
From Preferred and avoided codon pairs in three domains of life (2008) · cites this paper as [16]
The Discussion reports significant interactions between a codon’s third nucleotide (cP3) and nucleotides in the following A-site codon. But it calls cP3 itself cardinal to pairing frequencies, so it does not locate the main effects solely in nucleotides following the codon. No page number is available in our copy. (LLM, conf=0.82)
Experimental — accuracy not yet measuredSpecific preferred or avoided nucleotide patterns differ among species.
“It has been found that the specific preferred or avoided nucleotide patterns differ among species [16,22].”
From Preferred and avoided codon pairs in three domains of life (2008) · cites this paper as [16]
Effects of codon context are influenced by physical interactions between tRNA isoacceptors in the ribosomal P- and A-sites.
“Previous studies suggest that the effects of codon context are influenced by the physical interactions between tRNA isoacceptors in the ribosomal P- and A-sites [1,16,23].”
From Preferred and avoided codon pairs in three domains of life (2008) · cites this paper as [16]
In five gamma proteobacteria, Bacillus subtilis and two yeasts, A-site codons decoded by the same tRNA have similar patterns of P-site codon pairing preference.
“It has been shown that in five gamma proteobacteria, Bacillus subtilis and two yeasts, the A-site codons decoded by the same tRNA have similar patterns of P-site codon pairing preference [16].”
From Preferred and avoided codon pairs in three domains of life (2008) · cites this paper as [16]
Codon context might be influenced by certain structural constraints imposed by two tRNAs occupying the ribosomal P- and A-sites.
“In addition, it has been suggested that codon context might be influenced by certain structural constraints imposed by two tRNAs occupying the ribosomal P- and A-sites [1,16,23].”
From Preferred and avoided codon pairs in three domains of life (2008) · cites this paper as [16]
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- Authors
- Buchan, J. R.
- Affiliations
- University of Aberdeen (GB)
- Corresponding author
- Buchan, J. R.
- ORCID
- Buchan, J. R.
- Venue
- Nucleic Acids Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2006-02-06
- Volume
- 34
- Issue
- 3
- Pages
- 1015-1027
- ISSN
- 0305-1048 (ISSN-L)
- 1362-4962
- PMC
- PMC1363775
- OpenAlex
- W2162592907
- Cited by
- 108
- References
- 51
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 4 · 2023: 6 · 2022: 4 · 2021: 7 · 2020: 8 · 2019: 7 · 2018: 2 · 2017: 12 · 2016: 4 · 2015: 9 · 2014: 9 · 2013: 5 · 2012: 6
- FWCI
- 1.91
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- other-oa
- Locations
- Nucleic Acids Research (publishedVersion, other-oa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Tenovus
- Biotechnology and Biological Sciences Research Council
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA modifications and cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Keywords
- tRNA, ribosomal A site, ribosomal P site, translation elongation, rare codons, tRNA structure, translation fidelity, open reading frames, Bacillus subtilis, Gammaproteobacteria, eukaryotes, prokaryotes
- MeSH terms
- Bacillus subtilis, Bacteria, Codon, RNA, Transfer, Yeasts, Cluster Analysis, Open Reading Frames, Base Pairing, Gammaproteobacteria, Genomics
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