Origins of Life and Evolution of Biospheres

, Volume 35, Issue 3, pp 275–295

On the Structural Regularity in Nucleobases and Amino Acids and Relationship to the Origin and Evolution of the Genetic Code

Genetic Code Origins


To explore how chemical structures of both nucleobases and amino acids may have played a role in shaping the genetic code, numbers of sp2 hybrid nitrogen atoms in nucleobases were taken as a determinative measure for empirical stereo-electronic property to analyze the genetic code. Results revealed that amino acid hydropathy correlates strongly with the sp2 nitrogen atom numbers in nucleobases rather than with the overall electronic property such as redox potentials of the bases, reflecting that stereo-electronic property of bases may play a role. In the rearranged code, five simple but stereo-structurally distinctive amino acids (Gly, Pro, Val, Thr and Ala) and their codon quartets form a crossed intersection “core”. Secondly, a re-categorization of the amino acids according to their β-carbon stereochemistry, verified by charge density (at β-carbon) calculation, results in five groups of stereo-structurally distinctive amino acids, the group leaders of which are Gly, Pro, Val, Thr and Ala, remarkably overlapping the above “core”. These two lines of independent observations provide empirical arguments for a contention that a seemingly “frozen” “core” could have formed at a certain evolutionary stage. The possible existence of this codon “core” is in conformity with a previous evolutionary model whereby stereochemical interactions may have shaped the code. Moreover, the genetic code listed in UCGA succession together with this codon “core” has recently facilitated an identification of the unprecedented icosikaioctagon symmetry and bi-pyramidal nature of the genetic code.


amino acid classification charge distribution coevolution β-C stereochemistry determinative measure frozen core nitrogen atom hybrid sp2 nucleobase redox potentials rearranged genetic code stereo-electronic factor 


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  1. Alberty, S.: 2001, Physical Chemistry, 3rd ed., John Wiley & Sons, Inc., Chapter 11, p. 418.Google Scholar
  2. Balasubramanian, R., Seetharamulu, P. and Raghunathan, G.: 1980, A Conformational Rationale for the Origin of the Mechanism of Nucleic Acid-Directed Protein Synthesis of ‘Living’ Organisms, Origins Life 10, 15–30.CrossRefGoogle Scholar
  3. Cedergren, R. and Miramontes, P.: 1996, The Puzzling Origin of the Genetic Code, Trends Biochem. Sci. 21, 199–200. Erratum in: 1996, Trends Biochem. Sci. 21, 396. Comment in: 1997, Trends Biochem. Sci. 22, 49–50.Google Scholar
  4. Crick, F. H. C.: 1968, The Origin of the Genetic Code, J. Mol. Biol. 38, 367–379.CrossRefPubMedGoogle Scholar
  5. Davydov, O. V.: 1998, Amino Acid Contribution to the Genetic Code Structure: End-Atom Chemical Rules of Doublet Composition, J. Theor. Biol. 193, 679–690.CrossRefPubMedGoogle Scholar
  6. Di Giulio, M., Capobianco, M. R. and Medugno, M.: 1994, On the Optimization of the Physicochemical Distances Between Amino Acids in the Evolution of the Genetic Code, J. Theor. Biol. 168, 43–51.CrossRefPubMedGoogle Scholar
  7. Di Giulio, M. and Medugno, M.: 1998, The Historical Factor: The Biosynthetic Relationships Between Amino Acids and Their Physicochemical Properties in the Origin of the Genetic Code, J. Mol. Evol. 46, 615–621.PubMedGoogle Scholar
  8. Di Giulio, M. and Medugno, M.: 2001, The Level and Landscape of Optimization in the Origin of the Genetic Code, J. Mol. Evol. 52, 372–382.PubMedGoogle Scholar
  9. D'Onofrio, G., Jabbari, K., Musto, H. and Bernardi, D.: 1999, The Correlation of Protein Hydropathy with the Base Composition of Coding Sequences, Gene 238, 3–14.CrossRefPubMedGoogle Scholar
  10. Döring, V., Mootz, H. D., Nangle, L. A., Hendrickson, T. L., de Crécy-Lagard, V., Schimmel, P. and Marliére, P.: 2001, Enlarging the Amino Acid Set of Escherichia Coli by Infiltration of the Valine Coding Pathway, Science 292, 501–504.PubMedGoogle Scholar
  11. Dufton, M. J.: 1997, Genetic Synonym Quotas and Amino Acid Complexity: Cutting the Cost of Proteins? J. Theor. Biol. 187, 165–173.CrossRefPubMedGoogle Scholar
  12. Eigen, M.: 1971, Self-Organization of Matter and the Evolution of Biological Macromolecules, Naturwiss 58, 465–532.CrossRefPubMedGoogle Scholar
  13. Eigen, M. and Schuster, P.: 1977, The Hypercycle. A Principle of Natural Self-Organization. Part A: Emergence of the hypercycle, Naturwissenschaften 64, 541–565.CrossRefPubMedGoogle Scholar
  14. Eigen, M. and Schuster, P.: 1978, The Hypercycle. A Principle of Natural Self-Organization. Part C: The Realistic Hypercycle, Naturwissenschaften 65, 341–369.CrossRefGoogle Scholar
  15. Eigen, M. and Schuster, P.: 1979, The Hypercycle: A Principle of Natural Self-Organization, Springer-Verlag, Heidelberg.Google Scholar
  16. Eigen, M., Gardiner, W., Schuster, P. and Winkler-Oswatitsch, R.: 1981, The Origin of Genetic Information, Sci. Am. 244, 88–92, 96.PubMedGoogle Scholar
  17. Engelman, D. M., Steitz, T. A. and Goldman, A.: 1986, Identifying Nonpolar Transbilayer Helices in Amino Acid Sequences of Membrane Proteins, Annu. Rev. Biophys. Biophys. Chem. 15, 321–353.CrossRefPubMedGoogle Scholar
  18. Fitch, W. and Upper, K.: 1987, The Phylogeny of tRNA Sequences Provides Evidence for Ambiguity Reduction in the Origin of the Genetic Code, Cold Spring Harbor Symp. Quant. Biol. 52, 759–767.PubMedGoogle Scholar
  19. Grafstein, D.: 1983, Stereochemical Origins of the Genetic Code, J. Theor. Biol. 105, 157–174.CrossRefPubMedGoogle Scholar
  20. Grantham, R.: 1980, Working on the Genetic Code, Trends Biochem. Sci. 5, 327–333.CrossRefGoogle Scholar
  21. Hartman, H.: 1995, Speculations on the Origin of the Genetic Code, J. Mol. Evol. 40, 541–544.CrossRefPubMedGoogle Scholar
  22. Houen, G.: 1999, Evolution of the Genetic Code: The Nonsense, Antisense, and Antinonsense Codes Make No Sense, BioSystems 54, 39–46.CrossRefPubMedGoogle Scholar
  23. Jiménez-Montaño, M. A., de la Mora-Basañez, R. and Pöschel, T.: 1996, The Hyperstructure of the Genetic Code Explains Conservative and Non-Conservative Amino Acid Substitutions In Vivo and In Vitro, BioSystems 39, 117–125.CrossRefPubMedGoogle Scholar
  24. Jiménez-Montaño, M. A.: 1999, Protein Evolution Drives the Evolution of the Genetic Code and Vice Versa, BioSystems 54, 47–64.CrossRefPubMedGoogle Scholar
  25. Jungck, J. R.: 1978, The Genetic Code as a Periodic Table, J. Mol. Evol. 11, 211–224.CrossRefPubMedGoogle Scholar
  26. Klump, H. H.: 1993, The Physical Bases of the Genetic Code: The Choice Between Speed and Precision, Archv. Biochem. Biophys. 301, 207–209.CrossRefGoogle Scholar
  27. Knight, R. D., Freeland, S. J. and Landweber, L. F.: 1999, Selection, History and Chemistry: The Three Faces of the Genetic Code, Trends Biochem. Sci. 24, 241–247.CrossRefPubMedGoogle Scholar
  28. Knight, R. D. and Landweber, L. F: 1998, Rhyme or Reason: RNA–Arginine Interactions and the Genetic Code, Chem. Biol. 5, R215–R220.CrossRefPubMedGoogle Scholar
  29. Kyte, J. and Doolittle, R. F.: 1982, A Simple Method for Displaying the Hydropathic Character of a Protein, J. Mol. Biol. 157, 105–132.CrossRefPubMedGoogle Scholar
  30. Lacey, J. C. Jr. and Mullins, D. W. Jr.: 1983, Experimental Studies Related to the Origin of the Genetic Code and the Process of Protein Synthesis – A Review, Origins Life 13, 3–42.CrossRefGoogle Scholar
  31. Lacey, J. C. Jr., Wickramasinghe, N. S. M. D. and Cook, G. W: 1992, Experimental Studies on the Origin of the Genetic Code and the Process of Protein Synthesis: A Review Update, Orig. Life Evol. Biosph. 22, 243–275.CrossRefPubMedGoogle Scholar
  32. Lehmann, J.: 2000, Physico-Chemical Constraints Connected with the Coding Properties of the Genetic System, J. Theor. Biol. 202, 129–144.CrossRefPubMedGoogle Scholar
  33. Luo, L.-F. and Li, X.: 2002, Construction of Genetic Code from Evolutionary Stability, BioSystems 65, 83–97.CrossRefPubMedGoogle Scholar
  34. Miller, S. L.: 1987, Which Organic Compounds Could have Occurred on the Prebiotic Earth? Cold Spring Harb. Symp. Quant. Biol. 52, 17–27.PubMedGoogle Scholar
  35. Minegishi, S. and Mayr, H.: 2003, How Constant are Ritchie's “Constant Selectivity Relationships”? A General Reactivity Scale for n-, pi-, and Sigma-Nucleophiles, J. Am. Chem. Soc. 125, 286–295.CrossRefPubMedGoogle Scholar
  36. Nelson, D. L. and Cox, M. M.: 2000, Lehninger Principles of Biochemistry, Worth Publishers, New York.Google Scholar
  37. Pastushenko, V. Ph. and Pastushenko, A. V.: 1997, A Correlation Between the Genetic Code and the Structure and Electrical Properties of Bio Amino Acids, Bioelectrochem. Bioenerg. 44, 23–29.CrossRefGoogle Scholar
  38. Qiu, Y. and Zhu, L.: 2000, The Rearranged Genetic Code and Its Implications in Evolution and Biochemistry, BioSystems 56, 139–144.CrossRefPubMedGoogle Scholar
  39. Rakocevic, M. and Jokic, A.: 1996, Four Stereochemical Types of Protein Amino Acids: Synchronic Determination with Chemical Characteristics, Atom and Nucleon Number, J. Theor. Biol. 183, 345–349.CrossRefPubMedGoogle Scholar
  40. Rodin, S., Ohno, S. and Rodin, A.: 1993, Transfer RNAs with Complementary Anticodons: Could they Reflect Early Evolution of Discriminative Genetic Code Adaptors? Proc. Natl. Acad. Sci. U.S.A. 90, 4723–4727.PubMedGoogle Scholar
  41. Ronneberg, T. A., Landweber, L. F. and Freeland, S. J.: 2000, Testing a Biosynthetic Theory of the Genetic Code: Fact or Artifact? Proc. Natl. Acad. Sci. U.S.A. 97, 13690–13695.CrossRefPubMedGoogle Scholar
  42. Seidel, C. A. M., Schulz, A. and Sauer, M. H. M.: 1996, Nucleobase-Specific Quenching of Fluorescent Dyes. 1. Nucleobase One-Electron Redox Potentials and Their Correlation with Static and Dynamic Quenching Efficiencies, J. Phy. Chem. 100, 5541–5553.CrossRefGoogle Scholar
  43. Shcherbak, V. I.: 1993, Twenty Canonical Amino Acids of the Genetic Code: The Arithmetical Regularity, J. Theor. Biol. 162, 399–401.CrossRefPubMedGoogle Scholar
  44. Shimizu, M.: 1982, Molecular Basis for the Genetic Code, J. Mol. Evol. 18, 297–303.CrossRefPubMedGoogle Scholar
  45. Siegbahn, P. E. M. and Blomberg, M. R. A.: 2000, Transition-Metal Systems in Biochemistry Studied by High-Accuracy Quantum Chemistry Methods, Chem. Rev. 100, 421–437.CrossRefPubMedGoogle Scholar
  46. Siemion, I. Z. and Stefanowicz, P.: 1992, Periodical Changes of Amino Acid Reactivity within the Genetic Code, BioSystems 27, 77–84.CrossRefPubMedGoogle Scholar
  47. Sjostrom, M. and Wold, S.: 1985, A Multivariate Study of the Relationship Between the Genetic Code and the Physical-Chemical Properties of Amino Acids, J. Mol. Evol. 22, 272–277.CrossRefPubMedGoogle Scholar
  48. Swanson, R.: 1984, A Unifying Concept for the Amino Acid Code, Bull. Math. Biol. 46, 187–203.CrossRefPubMedGoogle Scholar
  49. Szathmary, E.: 1999, The Origin of the Genetic Code-Amino Acids as Cofactors in an RNA World, Trends Genet. 15, 223–229.CrossRefPubMedGoogle Scholar
  50. Taylor, F. J. R. and Coates, D.: 1989, The Code Within the Codons, BioSystems 22, 177–187.CrossRefPubMedGoogle Scholar
  51. Trifonov, E. N. and Bettecken, T.: 1997, Sequence Fossils, Triplet Expansion, and Reconstruction of Earliest Codons, Gene 205, 1–6.CrossRefPubMedGoogle Scholar
  52. Trifonov, E. N.: 2000, Consensus Temporal Order of Amino Acids and Evolution of the Triplet Code, Gene 261, 139–151.CrossRefPubMedGoogle Scholar
  53. Wang, L., Brock, A., Herberich, B. and Schultz, P. G.: 2001, Expanding the Genetic Code of Escherichia Coli, Science 292, 498–500.PubMedMathSciNetGoogle Scholar
  54. Weber, A. L. and Lacey, J. C. Jr.: 1978, Genetic Code Correlations: Amino Acids and Their Anticodon Nucleotides, J. Mol. Evol. 11, 199–210.CrossRefPubMedGoogle Scholar
  55. Weber, A. L. and Miller, S. L.: 1981, Reasons for the Occurrence of the Twenty Coded Protein Amino Acids, J. Mol. Evol. 17, 273–284.CrossRefPubMedGoogle Scholar
  56. Woese, C. R.: 1965, On the Origin of the Genetic Code, Proc. Natl. Acad. Sci. U.S.A. 54, 1546–1552.PubMedGoogle Scholar
  57. Woese, C. R., Dugre, D. H., Dugre, S. A., Kondo, M. and Saxinger, W. C.: 1966, On the Fundamental Nature and Evolution of the Genetic Code, Cold Spring Harbor Symp. Quant. Biol. 31, 723–736.PubMedGoogle Scholar
  58. Woese, C. R., Dugre, D. H., Saxinger, W. C. and Dugre, S. A.: 1966, The Molecular Basis for the Genetic Code, Proc. Natl. Acad. Sci. U.S.A. 55, 966–974.PubMedGoogle Scholar
  59. Woese, C. R.: 1967, The Genetic Code, Harper & Row, New York.Google Scholar
  60. Wong, J. T.: 1975, A Co-Evolution Theory of the Genetic Code, Proc. Natl. Acad. Sci. U.S.A. 72, 1909–1912.PubMedGoogle Scholar
  61. Wong, J. T. and Bronskill, P. M.: 1979, J. Mol. Evol. 13, 115–125.CrossRefPubMedGoogle Scholar
  62. Yang, C. M. and Chen, Y.: 2000, Protein Only or Virino? Chin. Sci. Bull. 45, 285–289.Google Scholar
  63. Yang, C. M.: 2000, An “i-4, i, i+4” “Reductive and Nucleophilic Zipper” Shared by Both Prion Protein and Beta-Amyloid Peptide Sequences Supports a Common Putative Molecular Mechanism, Chem. J., Internet
  64. Yang, C. M., Li, W., Hang, Q. and Cheng, J. P.: 2001, Protein Chemical Biology in Neurodegenerative Disorders, Prog. Nat. Sci. 1, 673–681.Google Scholar
  65. Yang, C. M.: 2002, Physical Organic Chemistry in Neurodegenerative Diseases, Chem. J. Chin. Univ. 23, 243–250.Google Scholar
  66. Yang, C. M.: 2003, On the quasi-icosikaioctagon (quasi-28-gon) Symmetry and Presumed Evolutionary Axes of the Genetic Code,, submitted for publication.
  67. Yarus, M.: 1998, Amino Acids as RNA Ligands: A Direct-RNA-Template Theory for the Code's Origin, J. Mol. Evol. 47, 109–117.PubMedGoogle Scholar
  68. Yarus, M.: 2000, RNA-Ligand Chemistry: A Testable Source for the Genetic Code, RNA 6, 475–484.CrossRefPubMedGoogle Scholar
  69. Ycas, M.: 1999, Codons and Hypercycles, Orig. Life Evol. Biosph. 29, 95–108.CrossRefPubMedGoogle Scholar

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© Springer Science + Business Media, Inc. 2005

Authors and Affiliations

  1. 1.Neurochemistry and System Chemical BiologyNankai UniversityTian JinChina

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