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Journal of Molecular Evolution

, Volume 57, Issue 6, pp 694–701 | Cite as

Mammalian Mutation Pressure, Synonymous Codon Choice, and mRNA Degradation

  • Jubao Duan
  • Marcos A. AntezanaEmail author
Article

Abstract

The usage of synonymous codons (SCs) in mammalian genes is highly correlated with local base composition and is therefore thought to be determined by mutation pressure. The usage is nonetheless structured. For instance, mammals share with Saccharomyces and Drosophila most preferences for the C-ending over the G-ending codon (or vice versa) within each fourfold-degenerate SC family and the fact that their SCs are placed along coding regions in ways that minimize the number of T|A and C|G dinucleotides (“|” being the codon boundary). TA and CG underrepresentations are observed everywhere in the mammalian genome affecting the SC usage, the amino acid composition of proteins, and the primary structure of introns and noncoding DNA. While the rarity of CG is ascribed to the high mutability of this dinucleotide, the rarity of TA in coding regions is considered adaptive because UA dinucleotides are cleaved by endoribonucleases. Here we present in vivo experimental evidence indicating that the number of T|A and/or C|G dinucleotides of a human gene can affect strongly the expression level and degradation of its mRNA. Our results are consistent with indirect evidence produced by other workers and with the detailed work that has been devoted to characterize UA cleavage in vitro and in vivo. We conclude that SC choice can influence strongly mRNA function and gene expression through effects not directly related to the codon–anticodon interaction. These effects should constrain heavily the nucleotide motif composition of the most abundant mRNAs in the transcriptome, in particular, their SC usage, a usage that must be reflected by cellular tRNA concentrations and thus defines for all other genes which SCs are translated fastest and most accurately. Furthermore, the need to avoid such effects genome-wide appears serious enough to have favored the evolution of biases in context-dependent mutation that reduce the occurrence of intrinsically unfavorable motifs, and/or, when possible, to have induced the molecular machinery mediating such effects to rely opportunistically on already existing motif rarities and abundances. This may explain why nucleotide motif preferences are very similar in transcribed and nontranscribed mammalian DNA even though the preferences appear to be adaptive only in transcribed DNA.

Keywords

Synonymous codon Codon usage Mammalian Human Mutation Context-dependent mutation Noncoding region Transcribed region Transcriptome tRNA pools mRNA Codon usage bias UA CG TA Dinucleotide Endoribonuclease Target sequence Cleavage Secondary structure Primary structure mRNA degradation mRNA decay mRNA translatability 

Notes

Acknowledgements

We thank Elliott Gershon, Marry Kreitman, Carlos C Machado, Ira Wool, Matthew Meselson, and an anonymous reviewer for comments, advice, literature indications, and/or encouragement; and Janice Spofford, Martha Hamblin, Esther Betran, Lisa Noble, Donovan Conrad, Antonio Grinbergo, Charles Langley, Wolfgang Stephan, Peter Stadler, Mactias Gerberding, and Shin-Han Hui for comments and/or editorial advice. The synthetic sequences were financed by a grant from The University of Chicago’s Brain Research Foundation to M.A. Antezana and Pablo Gejman. J. Duan was supported by a NARSAD Young Investigator Award. We warmly thank P. Gejman for his enthusiastic belief in the project, for the use of his laboratory and supplies, and for salary support.

References

  1. 1.
    Antezana, MA, Kreitman, M 1999The nonrandom location of synonymous codons suggests that reading frame-independent forces have patterned codon preferences.J Mol Evol493643PubMedGoogle Scholar
  2. 2.
    Antezana MA, Kreitman M. Unpublished dataGoogle Scholar
  3. 3.
    Bennetzen, JL, Hall, BD 1982Codon selection in yeast.J Biol Chem25730263031PubMedGoogle Scholar
  4. 4.
    Berg, OG, Silva, PJ 1997Codon bias in Escherichia coli: The influence of codon context on mutation and selection.Nucleic Acids Res2513971404CrossRefPubMedGoogle Scholar
  5. 5.
    Beutler, E, Gelbart, T, Han, JH, Koziol, JA, Beutler, B 1989Evolution of the genome and the genetic code: Selection at the dinucleotide level by methylation and polyribonucleotide cleavage.Proc Natl Acad Sci USA86192196PubMedGoogle Scholar
  6. 6.
    Candelas, G, Candelas, T, Ortiz, A, Rodriguez, O 1983Translational pauses during a spider fibroin synthesis.Biochem Biophys Res Commun11610331038PubMedGoogle Scholar
  7. 7.
    Caponigro, G, Parker, R 1996Mechanisms and control of mRNA turnover in Saccharomyces cerevisiae.Microbiol Rev60233249PubMedGoogle Scholar
  8. 8.
    Chavancy, G, Garel, JP 1981Does quantitative tRNA adaptation to codon content in mRNA optimize the ribosomal translation efficiency? Proposal for a translation system model.Biochimie63187195PubMedGoogle Scholar
  9. 9.
    Deana, A, Ehrlich, R, Reiss, C 1996Synonymous codon selection controls in vivo turnover and amount of mRNA in Escherichia coli bla and ompA genes.J Bacteriol17827182720PubMedGoogle Scholar
  10. 10.
    Duret, L, Galtier, N 2000The covariation between TpA deficiency, CpG deficiency, and G+C content of human isochores is due to a mathematical artifact.Mol Biol Evol1716201625PubMedGoogle Scholar
  11. 11.
    Eichler, DC, Eales, SJ 1983The effect of RNA secondary structure on the action of a nucleolar endoribonuclease.J Biol Chem2581004910053PubMedGoogle Scholar
  12. 12.
    Eichler, DC, Tatar, TF 1980Properties of a purified nucleolar ribonuclease from Ehrlich ascites carcinoma cells.Biochemistry1930163022PubMedGoogle Scholar
  13. 13.
    Fiers, W, Contreras, R, Haegeman, G, Rogiers, R, Van de Voorde, A, Van Heuverswyn, H, Van Herreweghe, J, Volckaert, G, Ysebaert, M 1978Complete nucleotide-sequence of SV40 DNA.Nature273113120PubMedGoogle Scholar
  14. 14.
    Grantham, R, Gautier, C, Gouy, M, Jacobzone, M, Mercier, R 1981Codon catalog usage is a genome strategy modulated for gene expressivity.Nucleic Acids Res9R43R74PubMedGoogle Scholar
  15. 15.
    Grosjean, H, Freirs, W 1982Preferential codon usage in prokaryotic genes: The optimal codon-anti-codon interaction energy and the selective codon usage in efficiently expressed genes.Gene18199209CrossRefPubMedGoogle Scholar
  16. 16.
    Hoekema, A, Kastelein, RA, Vasser, M, de Boer, HA 1987Codon replacement in the PGK1 gene of Saccharomyces cerevisiae: Experimental approach to study the role of biased codon usage in gene expression.Mol Cell Biol729142924PubMedGoogle Scholar
  17. 17.
    Josse, J, Kaiser, AD, Kornberg, A 1961Enzymatic synthesis of deoxyribonucleic acid. 8. Frequencies of nearest neighbor base sequences in deoxyribonucleic acid.J Biol Chem236864875PubMedGoogle Scholar
  18. 18.
    Kafatos, FC, Efstratiadis, A, Forget, BG, Weissman, SM 1977Molecular evolution of human and rabbit beta-globin mRNAs. Molecular evolution of human and rabbit beta-globin messenger-RNAs.Proc Natl Acad Sci USA7456185622PubMedGoogle Scholar
  19. 19.
    Karlin, S, Burge, C 1995Dinucleotide relative abundance extremes: A genomic signature.Trends Genet11283290PubMedGoogle Scholar
  20. 20.
    Konu, O, Li, MD 2002Correlations between mRNA expression levels and GC contents of coding and untranslated regions of genes in rodents.J Mol Evol543541PubMedGoogle Scholar
  21. 21.
    Lemm, I, Ross, J 2002Regulation of c-myc mRNA decay by translational pausing in a coding region instability determinant.Mol Cell Biol2239593969CrossRefPubMedGoogle Scholar
  22. 22.
    Lennon, GG, Fraser, NW 1983CpG frequency in large DNA segments.J Mol Evol19286288PubMedGoogle Scholar
  23. 23.
    Lustig, F, Boren, T, Claesson, C, Simonsson, C, Barcisszewska, M, Lagerkvist, U 1993The nucleotide in position 33 of the tRNA anticodon loop determines ability of anticodon UCC to discriminate among glycine codons.Proc Natl Acad Sci USA9033433347PubMedGoogle Scholar
  24. 24.
    Nussinov, R 1981aEukaryotic dinucleotide preference rules and their implications for degenerate codon usage.J Mol Biol149125131Google Scholar
  25. 25.
    Nussinov, R 1981bNearest neighbor nucleotide patterns. Structural and biological implications.J Biol Chem25684588462Google Scholar
  26. 26.
    Oprea, M, Cowell, LG, Kepler, TB 2001The targeting of somatic hypermutation closely resembles that of meiotic mutation.J Immunol166892899PubMedGoogle Scholar
  27. 27.
    Parker, J 1989Errors and alternatives in reading the universal genetic code.Microbiol Rev53273298PubMedGoogle Scholar
  28. 28.
    Parker, R, Jacobson, A 1990Translation and a 42-nucleotide segment within the coding region of the mRNA encoded by the MAT alpha 1 gene are involved in promoting rapid mRNA decay in yeast.Proc Natl Acad Sci USA8727802784PubMedGoogle Scholar
  29. 29.
    Perlak, FJ, Fuchs, RL, Dean, DA, McPherson, SL, Fischhoff, DA 1991Modification of the coding sequence enhances plant expression of insect control protein genes.Proc Natl Acad Sci USA8833243328PubMedGoogle Scholar
  30. 30.
    Post, LE, Nomura, M 1979Nucleotide sequence of the intercistronic region preceding the gene for RNA polymerase subunit alpha in Escherichia coli.Biol Chem2541060410606Google Scholar
  31. 31.
    Post, LE, Strycharz, GD, Nomura, M, Lewis, H, Dennis, PP 1979Nucleotide sequence of the ribosomal protein gene cluster adjacent to the gene for RNA polymerase subunit beta in Escherichia coli.Proc Natl Acad Sci USA7616971701PubMedGoogle Scholar
  32. 32.
    Precup, J, Parker, J 1987Missense misreading of asparagine codons as a function of codon identity and context.Biol Chem2621135111355Google Scholar
  33. 33.
    Qiu, L, Moreira, A, Kaplan, G, Levitz, R, Wang, JY, Xu, C, Drlica, K 1998Degradation of hammerhead ribozymes by human ribonucleases.Mol Gen Genet258352362CrossRefPubMedGoogle Scholar
  34. 34.
    Russell, GJ, Subak-Sharpe, JH 1967Similarity of the general designs of protochordates and invertebrates.Nature266533536Google Scholar
  35. 35.
    Salser, W 1978Globin mRNA sequences: Analysis of base pairing and evolutionary implications.Cold Spring Harbor Symp Quant Biol429851002PubMedGoogle Scholar
  36. 36.
    Seffens, W, Digby, D 1999mRNAs have greater negative folding free energies than shuffled or codon choice randomized sequences.Nucleic Acids Res2715781584CrossRefPubMedGoogle Scholar
  37. 37.
    Setlow, P 1976.Fasman, GD eds. Handbook of biochemistry and molecular biology.CRC PressCleveland, OH312318Google Scholar
  38. 38.
    Smith, DS, Creadon, G, Jena, PK, Portanova, JP, Kotzin, BL, Wysocki, LJ 1996Di- and trinucleotide target preferences of somatic mutagenesis in normal and autoreactive B cells.J Immunol15626422652PubMedGoogle Scholar
  39. 39.
    Urrutia, AO, Hurst, LD 2001Codon usage bias covaries with expression breadth and the rate of synonymous evolution in humans, but this is not evidence for selection.Genetics5911911199Google Scholar
  40. 40.
    Williamson, JR 1994G-quartet structures in telomeric DNA.Annu Rev Biophys Biomol Struct23703730CrossRefPubMedGoogle Scholar
  41. 41.
    Workman, C, Krogh, A 1999No evidence that mRNAs have lower folding free energies than random sequences with the same dinucleotide distribution.Nucleic Acids Res.2748164822CrossRefPubMedGoogle Scholar
  42. 42.
    Zama, M 1997Translational pauses during the synthesis of proteins and mRNA structure.Nucleic Acids Symp Ser37179180PubMedGoogle Scholar
  43. 43.
    Zhou, J, Liu, WJ, Peng, SW, Sun, XY, Frazer, I 1999Papillomavirus capsid protein expression level depends on the match between codon usage and tRNA availability.J Virol7349724982PubMedGoogle Scholar
  44. 44.
    Zolotukhin, S, Potter, M, Hauswirth, WW, Guy, J, Muzyczka, N 1996A “humanized” green fluorescent protein cDNA adapted for high-level expression in mammalian cells.J Virol7046464654PubMedGoogle Scholar

Copyright information

© Springer-Verlag New York Inc. 2003

Authors and Affiliations

  1. 1.Department of PsychiatryThe University of Chicago, 924 East 57th Street, R-004, Chicago, IL 60637USA

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