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Codon Usage Decreases the Error Minimization Within the Genetic Code

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Abstract

The genetic code is not random but instead is organized in such a way that single nucleotide substitutions are more likely to result in changes between similar amino acids. This fidelity, or error minimization, has been proposed to be an adaptation within the genetic code. Many models have been proposed to measure this adaptation within the genetic code. However, we find that none of these consider codon usage differences between species. Furthermore, use of different indices of amino acid physicochemical characteristics leads to different estimations of this adaptation within the code. In this study, we try to establish a more accurate model to address this problem. In our model, a weighting scheme is established for mistranslation biases of the three different codon positions, transition/transversion biases, and codon usage. Different indices of amino acids’ physicochemical characteristics are also considered. In contrast to pervious work, our results show that the natural genetic code is not fully optimized for error minimization. The genetic code, therefore, is not the most optimized one for error minimization, but one that balances between flexibility and fidelity for different species.

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Acknowledgements

The authors sincerely appreciate Zhen Yao and Zhi-Hong Zhang for instructive advice on programming. In addition, we thank Prof. Yang Zhong, Dr. Li-Ying Cui, and Dr. Thomas Merritt for helpful discussions. We are also very gratitude to anonymous referees for very informative comments on the manuscript. C.-T. Zhu (Zhu Lei) is supported by a Chun-Tsung fellowship at Fudan University endowed by Tsung-Dao Lee, 1957 Nobel Prize laureate in physics.

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Authors and Affiliations

  1. Department of Ecology and Evolution, State University of New York at Stony Brook, Stony Brook, NY 11794-5245, USA

    Chen-Tseh Zhu

  2. Laboratory of Biochemistry and Molecular Biology, Department of Biochemistry, School of Life Sciences, Fudan University, Shanghai, 200433, People’s Republic of China

    Xiao-Bin Zeng & Wei-Da Huang

Authors
  1. Chen-Tseh Zhu
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  2. Xiao-Bin Zeng
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  3. Wei-Da Huang
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Corresponding author

Correspondence to Wei-Da Huang.

Appendices

Appendix A

Let us, for convenience in describing the sums performed, refer to four bases by number; U = 1, C = 2, A = 3, and G = 4. Let the characteristic Q be specified by a corresponding base triple (L, M, N) of the amino acid. T is the quantification of combined weighting of mistranslation, transition, and transversion. U (L, M, N) is the codon usage of the triple (L, M, N). UWMS measurement can be defined as follows (stop codons are excluded).

Codon usage of a certain species is calculated from all the coding sequences of that species reported to GenBank. The codon usage of each codon is measured by the relative frequency of the count of that codon versus the count of all codons. Codon usage of a certain species is consequently a vector of 61 variables.

Codon usage data were obtained from the Codon Usage Database (ftp://www.kazusa.or.jp/ ) in August 1999 (Nakamura 1999).

Appendix B

A Delphi 3.0 program was written for calculation. The random codes have the same degenerate pattern as the natural code, only the positions of amino acids were changed. Four million codes are generated using a cycle function; in one cycle, 4000 codes are generated and calculated. In every cycle, the 4000 codes are all different. Although a code may be generated and calculated more than once in 1000 cycles, in such a big population, sampling with or without replacement has the same meaning.

The program and source code are available on request to the authors.

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Zhu, CT., Zeng, XB. & Huang, WD. Codon Usage Decreases the Error Minimization Within the Genetic Code . J Mol Evol 57, 533–537 (2003). https://doi.org/10.1007/s00239-003-2505-7

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  • DOI: https://doi.org/10.1007/s00239-003-2505-7

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