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Cited by 31RNA and protein synthesis mechanismsEvolution and Genetic DynamicsGenomics and Phylogenetic Studies

Selective forces and mutational biases drive stop codon usage in the human genome: a comparison with sense codon usage

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Trotta, Edoardo·2016·BMC Genomics
DOI 10.1186/s12864-016-2692-4PMC PMC4869280
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Abstract

BACKGROUND: The three stop codons UAA, UAG, and UGA signal the termination of mRNA translation. As a result of a mechanism that is not adequately understood, they are normally used with unequal frequencies. RESULTS: In this work, we showed that selective forces and mutational biases drive stop codon usage in the human genome. We found that, in respect to sense codons, stop codon usage was affected by stronger selective forces but was less influenced by neutral mutational biases. UGA is the most frequent termination codon in human genome. However, UAA was the preferred stop codon in genes with high breadth of expression, high level of expression, AT-rich coding sequences, housekeeping functions, and in gene ontology categories with the largest deviation from expected stop codon usage. Selective forces associated with the breadth and the level of expression favoured AT-rich sequences in the mRNA region including the stop site and its proximal 3'-UTR, but acted with scarce effects on sense codons, generating two regions, upstream and downstream of the stop codon, with strongly different base composition. By favouring low levels of GC-content, selection promoted labile local secondary structures at the stop site and its proximal 3'-UTR. The compositional and structural context favoured by selection was surprisingly emphasized in the class of ribosomal proteins and was consistent with sequence elements that increase the efficiency of translational termination. Stop codons were also heterogeneously distributed among chromosomes by a mechanism that was strongly correlated with the GC-content of coding sequences. CONCLUSIONS: In human genome, the nucleotide composition and the thermodynamic stability of stop codon site and its proximal 3'-UTR are correlated with the GC-content of coding sequences and with the breadth and the level of gene expression. In highly expressed genes stop codon usage is compositionally and structurally consistent with highly efficient translation termination signals.

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Authors
Trotta, E.
Affiliations
Istituto di Farmacologia Traslazionale (IT)
Corresponding author
Trotta, Edoardo
ORCID
Trotta, Edoardo
Venue
BMC Genomics
Publisher
Springer Science and Business Media LLC
Published
2016-05-17
Volume
17
Issue
1
Pages
366-366
ISSN
1471-2164 (ISSN-L)
DOI
10.1186/s12864-016-2692-4
PMC
PMC4869280
OpenAlex
W2403896150
Cited by
31
References
1
Citations by year
2026: 3 · 2025: 2 · 2024: 2 · 2023: 2 · 2022: 6 · 2021: 5 · 2020: 6 · 2019: 1 · 2018: 3
FWCI
0.57
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • BMC Genomics (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
Keywords
codon usage bias, mutational bias, natural selection, UGA, unnatural amino acids, UAG, GC content, gene expression breadth, ribosomal proteins, translation termination, human genome
MeSH terms
Base Composition, Codon, Gene Expression Regulation, Gene Frequency, Humans, Mutation, Selection, Genetic, Transcription, Genetic, Genome, Human, Open Reading Frames, Codon, Terminator, Evolution, Molecular, Computational Biology, Gene Expression Profiling, RNA Stability, Gene Ontology

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