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Related Experiment Videos

Codon choice and gene expression: synonymous codons differ in translational accuracy.

D B Dix1, R C Thompson

  • 1Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder 80309.

Proceedings of the National Academy of Sciences of the United States of America
|September 1, 1989
PubMed
Summary
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Different synonymous codons affect ribosome accuracy. Efficient codons, like UUC in E. coli, are less accurate, suggesting translational fidelity wasn't key in their evolution.

Area of Science:

  • Molecular Biology
  • Genetics
  • Biochemistry

Background:

  • Ribosomes translate messenger RNA (mRNA) into proteins using transfer RNA (tRNA).
  • Codon usage bias, the non-uniform use of synonymous codons, is observed in many organisms, including Escherichia coli.
  • The accuracy of translation depends on the ribosome's ability to discriminate between cognate and near-cognate tRNAs.

Purpose of the Study:

  • To investigate how synonymous codons influence the accuracy of tRNA selection by ribosomes.
  • To determine if codon-induced changes in discrimination affect translational fidelity.
  • To explore the evolutionary implications of biased codon usage in relation to translational accuracy.

Main Methods:

  • Utilizing in vitro assays to measure the discrimination of near-cognate aminoacylated tRNAs by ribosomes programmed with different synonymous codons (e.g., UUC vs. UUU, CUC vs. CUU).

Related Experiment Videos

  • Analyzing both the initial tRNA binding step and the subsequent proofreading step of translation.
  • Comparing the codon-induced changes in reaction rates for cognate versus near-cognate ternary complexes.

    • Main Results:

    • Ribosomes programmed with UUC showed reduced discrimination against near-cognate Leu-tRNAs compared to those programmed with UUU.
    • Ribosomes programmed with CUC exhibited less discrimination against near-cognate Phe-tRNA than those programmed with CUU.
    • The codon's influence on reaction rate was more pronounced with near-cognate tRNAs than cognate tRNAs, indicating that more efficient codons can be less accurate.
    • The preferential use of the efficient but inaccurate UUC codon in highly expressed E. coli mRNAs suggests accuracy maximization was not a primary driver for this codon choice.

    Conclusions:

    • Synonymous codons differentially impact ribosome accuracy by altering tRNA discrimination.
    • Translational efficiency, rather than maximal accuracy, may drive the selection of certain codons, like UUC, in highly expressed genes.
    • Evolutionary codon usage bias in E. coli may prioritize translational speed over absolute fidelity for specific codons.