Skip to main content
Log in

A New Classification Scheme of the Genetic Code

  • Published:
Journal of Molecular Evolution Aims and scope Submit manuscript

Abstract

Since the early days of the discovery of the genetic code nonrandom patterns have been searched for in the code in the hope of providing information about its origin and early evolution. Here we present a new classification scheme of the genetic code that is based on a binary representation of the purines and pyrimidines. This scheme reveals known patterns more clearly than the common one, for instance, the classification of strong, mixed, and weak codons as well as the ordering of codon families. Furthermore, new patterns have been found that have not been described before: Nearly all quantitative amino acid properties, such as Woese’s polarity and the specific volume, show a perfect correlation to Lagerkvist’s codon–anticodon binding strength. Our new scheme leads to new ideas about the evolution of the genetic code. It is hypothesized that it started with a binary doublet code and developed via a quaternary doublet code into the contemporary triplet code. Furthermore, arguments are presented against suggestions that a “simpler” code, where only the midbase was informational, was at the origin of the genetic code.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Figure 1
Figure 2

Similar content being viewed by others

References

  • S Alberti (1997) ArticleTitleThe origin of the genetic code and protein synthesis J Mol Evol 45 352–358

    Google Scholar 

  • B Alberts A Johnson J Lewis M Raff K Roberts P Walter (2002) Molecular biology of the cel Garland Science New York

    Google Scholar 

  • DH Ardell G Sella (2002) ArticleTitleNo accident: Genetic codes freeze in error-correcting patterns of the standard genetic code Phil Trans R Soc Lond B 357 1625–1642

    Google Scholar 

  • I Barzilay JL Sussman Y Lapidot (1973) ArticleTitleFurther studies on the chromatographic behaviour of dinucleoside monophosphates J Chromatogr 79 139–146

    Google Scholar 

  • DJ Brooks JR Fresco (2002) ArticleTitleIncreased frequency of cysteine, tyrosine, and phenylalanine residues since the last universal ancestor Mol Cell Prot 1 IssueID2 125–131

    Google Scholar 

  • DJ Brooks JR Fresco (2003) ArticleTitleGreater GNN pattern bias in sequence elements encoding conserved residues of ancient proteins may be an indicator of amino acid composition of early proteins Gene 303 177–185

    Google Scholar 

  • DJ Brooks JR Fresco AM Lesk M Singh (2002) ArticleTitleEvolution of amino acid frequencies in proteins over deep time: Inferred order of introduction of amino acids into the genetic code Mol Biol Evol 19 IssueID10 1645–1655

    Google Scholar 

  • HB Bull K Breese (1974) ArticleTitleSurface tension of amino acid solutions: a hydrophobicity scale of the amino acid residues Arch Biochem Biophys 161 665–670

    Google Scholar 

  • FHC Crick (1966) ArticleTitleCodon-anticodon pairing: The wobble hypothesis J Mol Biol 19 548–555

    Google Scholar 

  • FHC Crick (1968) ArticleTitleThe origin of the genetic code J Mol Biol 38 367–379

    Google Scholar 

  • P Dunnill (1966) ArticleTitleTriplet nucleotide–amino acid pairing: A stereochemical basis for the division between protein and nonprotein amino acids Nature 210 1267–1268

    Google Scholar 

  • M Eigen (1977) ArticleTitleThe hypercycle. A principle of natural self-organization. A: Emergence of the hypercycle Naturwissenschaften 64 541–565 Occurrence Handle1:CAS:528:DyaE1cXjtlGjtQ%3D%3D Occurrence Handle593400

    CAS  PubMed  Google Scholar 

  • M Eigen P Schuster (1978) ArticleTitleThe hypercycle: A principle of natural self-organization Naturwissenschaften 65 341–368

    Google Scholar 

  • Elzanowski A, Ostell J (2000) Genetic codes. http://www3.ncbi.nlm.nih.gov/htbin-post/Taxonomy/wprintgc?mode = t#SG1

  • WM Fitch K Upper (1987) ArticleTitleThe 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 Occurrence Handle1:CAS:528:DyaL1cXlt1Cmtrc%3D Occurrence Handle3454288

    CAS  PubMed  Google Scholar 

  • SJ Freeland (2002) ArticleTitleThe Darwinian genetic code: An adaptation for adapting? Genet Progam Evolv Machines 3 113–127

    Google Scholar 

  • SJ Freeland LD Hurst (1998) ArticleTitleThe genetic code is one in a million J Mol Evol 47 238–248 Occurrence Handle1:CAS:528:DyaK1cXmt1ansrs%3D Occurrence Handle9732450

    CAS  PubMed  Google Scholar 

  • SJ Freeland RD Knight LF Landweber LD Hurst (2000) ArticleTitleEarly fixation of an optimal genetic code Mol Biol Evol 17 511–518

    Google Scholar 

  • JP Garel D Filliol P Mandel (1973) ArticleTitleCoefficients de partage d’aminoacides, 1978 nucleobases, nucleosides et nucleotides dans un systeme solvant salin J Chromatogr 78 381–391

    Google Scholar 

  • R Grantham (1974) ArticleTitleAmino acid difference formula to help explain protein evolution Science 18S 862–864

    Google Scholar 

  • D Haig LD Hurst (1991) ArticleTitleA quantitative measure of error minimization in the genetic code J Mol Evol 33 412–417 Occurrence Handle1:CAS:528:DyaK3MXmsleqtrs%3D Occurrence Handle1960738

    CAS  PubMed  Google Scholar 

  • Halitsky D (2003) Extending the (hexa-)rhombic dodecahedral model of the genetic code: The code’s 6-fold degeneracies and the orthogonal projections of the 5-cube as 3-cube. Contributed paper (983-92-151), American Mathematical Society, and personal communication

  • M Hasegawa T Miyata (1980) ArticleTitleOn the antisymmetry of the amino acid code table Orig Life 10 265–270

    Google Scholar 

  • B Hayes (1998) ArticleTitleThe invention of the genetic code Am Sci 86 8–14

    Google Scholar 

  • JJ Hopfield (1978) ArticleTitleOrigin of the genetic code: A testable hypothesis based on tRNA structure, sequence, and kinetic proofreading Proc Natl Acad Sci USA 75 4334–4338

    Google Scholar 

  • A Jimenez-Sanchez (1995) ArticleTitleOn the origin and evolution of the genetic code J Mol Evol 41 712–716

    Google Scholar 

  • DD Jones (1975) ArticleTitleAmino acid properties and side-chain orientation in proteins: A cross correlation approach J Theor Biol 50 167–183

    Google Scholar 

  • TH Jukes (1973) ArticleTitlePossibilities for the evolution of the genetic code from a preceding form Nature 246 22–26

    Google Scholar 

  • JR Jungck (1971) ArticleTitlePre-Darwinian and non-Darwinian evolution of proteins Curr Mod Biol 3 307–318

    Google Scholar 

  • JR Jungck (1978) ArticleTitleThe genetic code as a periodic table J Mol Evol 11 211–224

    Google Scholar 

  • RD Knight LF Landweber (1998) ArticleTitleRhyme or reason: RNA-arginine interactions and the genetic code Chem Biol 5 R215–R220

    Google Scholar 

  • RD Knight LF Landweber (2000a) ArticleTitleGuilt by association: The arginine case revisited RNA 6 499–510

    Google Scholar 

  • RD Knight LF Landweber (2000b) ArticleTitleThe early evolution of the genetic code Cell 101 569–572

    Google Scholar 

  • RD Knight SJ Freeland LF Landweber (2001) ArticleTitleRewiring the keyboard: Evolvability of the genetic code Nat Rev Genet 2 49–58

    Google Scholar 

  • U Lagerkvist (1978) ArticleTitle“Two out of three”: An alternative method for codon reading Proc Natl Acad Sci USA 75 1759–1762

    Google Scholar 

  • U Lagerkvist (1981) ArticleTitleUnorthodox codon reading and the evolution of the genetic code Cell 23 305–306

    Google Scholar 

  • M Levitt (1976) ArticleTitleA simplified representation of protein conformations for rapid simulation of protein folding J Mol Biol 104 59–107

    Google Scholar 

  • M Levy SL Miller (1998) ArticleTitleThe stability of the RNA bases: Implications for the origin of life Proc Natl Acad Sci USA 95 7933–7938

    Google Scholar 

  • N Maizels AM Weiner (1987) ArticleTitlePeptide-specific ribosomes, genomic tags, and the origin of the genetic code Cold Spring Harb Symp Quant Biol 52 743–749

    Google Scholar 

  • JH McClendon (1986) ArticleTitleThe relationship between the origins of the biosynthetic paths to the amino acids and their coding Orig Life 16 269–270

    Google Scholar 

  • TL McMeekin ML Groves NJ Hipp (1964) Refractive indices of amino acids, proteins and related substances JA Stekol (Eds) Amino acids and serum proteins American Chemical Society Washington, DC 54–66

    Google Scholar 

  • SL Miller (1953) ArticleTitleProduction of amino acids under possible primitive earth conditions Science 117 528–529

    Google Scholar 

  • SL Miller (1987) ArticleTitleWhich organic compounds could have occurred on the prebiotic earth? Cold Spring Harb Symp Quant Biol 52 17–27

    Google Scholar 

  • LE Orgel (1968) ArticleTitleEvolution of the genetic apparatus J Mol Biol 38 381–393

    Google Scholar 

  • RL Ornstein JR Fresco (1983) ArticleTitleCorrelation of Tm, sequence, and ΔH of complementary RNA helices and comparison with DNA helices Biopolymers 22 2001–2016

    Google Scholar 

  • S Osawa TH Jukes K Watanabe A Muto (1992) ArticleTitleRecent evidence for the evolution of the genetic code Microbiol Rev 56 IssueID1 22–264

    Google Scholar 

  • JS Reader GF Joyce (2002) ArticleTitleA ribozyme composed of only two different nucleotides Nature 420 841–844

    Google Scholar 

  • TA Ronneberg LF Landweber SJ Freeland (2000) ArticleTitleTesting a biosynthetic theory of the genetic code: Fact or artifact? Proc Natl Acad Sci USA 97 13690–13695

    Google Scholar 

  • W Schwemmler (1994) Reconstruction of cell evolution: A periodic system of cells CRC Press Boca Raton, FL

    Google Scholar 

  • TM Sonneborn (1965) Degeneracy of the genetic code: extent, nature, and genetic implications V Bryson HJ Vogel (Eds) Evolving genes and proteins Academic Press New York 297–377

    Google Scholar 

  • E Szathmary (1992) ArticleTitleWhat is the optimum size for the genetic alphabet? Proc Natl Acad Sct USA 89 2614–2618

    Google Scholar 

  • E Szathmary (1993) ArticleTitleCoding coenzyme handles: A hypothesis for the origin of the genetic code Proc Natl Acad Sci USA 90 9916–9920

    Google Scholar 

  • E Szathmary (1999) ArticleTitleThe origin of the genetic code Trends Genet 15 223–229

    Google Scholar 

  • E Szathmary (2003) ArticleTitleWhy are there four letters in the genetic alphabet? Nat Rev Genet 4 995–1001

    Google Scholar 

  • FJR Taylor D Coates (1989) ArticleTitleThe code within the codons BioSystems 22 177–187

    Google Scholar 

  • M Thanbichler A Böck (2002) ArticleTitleThe function of SECIS RNA in translational control of gene expression in Escherichia coli EMBO J 21 6925–6934

    Google Scholar 

  • MD Topal JR Fresco (1976) ArticleTitleBase pairing and fidelity in codon-anticodon interaction Nature 263 289–293

    Google Scholar 

  • G Wächtershäuser (1988) ArticleTitleAn all-purine precursor of nucleic acids Proc Natl Acad Sci USA 85 1134–1135

    Google Scholar 

  • AL Weber JC Lacey SuffixJr (1978) ArticleTitleGenetic code correlations: amino acids and their anticodon nucleotides J Mol Evol 17 273–284

    Google Scholar 

  • AM Weiner N Maizels (1987) ArticleTitletRNA-like structures tag the 3′ ends of genomic RNA molecules for replication: Implications for the origin of protein synthesis Proc Natl Acad Sci USA 84 7383–7390

    Google Scholar 

  • CR Woese (1965) ArticleTitleOn the evolution of the genetic code Proc Natl Acad Sci USA 54 1546–1552 Occurrence Handle1:CAS:528:DyaF28Xltlagsg%3D%3D Occurrence Handle5218910

    CAS  PubMed  Google Scholar 

  • CR Woese (1967) The genetic code: The molecular basis for genetic expression Harper and Row New York

    Google Scholar 

  • CR Woese DH Dugre WC Saxinger SA Dugre (1966) ArticleTitleThe molecular basis for the genetic code Proc Natl Acad Sci USA 55 966–974

    Google Scholar 

  • CR Woese DH Dugre SA Dugre M Kondo WC Saxinger (1967) ArticleTitleOn the fundamental nature and evolution of the genetic code Cold Spring Harbor Symp Quant Biol 31 723–736

    Google Scholar 

  • RV Wolfenden PM Cullis CCF Southgate (1979) ArticleTitleWater, protein folding, and the genetic code Science 206 575–577

    Google Scholar 

  • JT-F Wong (1975) ArticleTitleA co-evolution theory of the genetic code Proc Natl Acad Sci USA 72 1909–1912 Occurrence Handle1:CAS:528:DyaE2MXkt1ertbg%3D Occurrence Handle1057181

    CAS  PubMed  Google Scholar 

  • M Yarus (1998) ArticleTitleAmino acids as RNA ligands: A direct-RNA-template theory for the code’s origin J Mol Evol 47 109–117

    Google Scholar 

  • M Yarus (2000) ArticleTitleRNA-ligand chemistry: A testable source for the genetic code RNA 6 475–484

    Google Scholar 

  • E Zuckerkandl L Pauling (1965) Evolutionary divergence and convergence in proteins V Bryson HS Vogel (Eds) Evolving genes and proteins Academic Press New York 97–167

    Google Scholar 

  • JM Zimmerman N Eliiezer R Simna (1968) ArticleTitle. J Theor Biol 21 170–201

    Google Scholar 

Download references

Acknowledgments

We thank two anonymous reviewers for many valuable comments and for referring us to relevant literature and A. Beyer, F. Grosse, M. Friedel, and M.-L. Merten for critical reading of the manuscript. This work was supported by Grant 0312704E from the Bundesministerium für Bildung und Forschung.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Thomas Wilhelm.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wilhelm, T., Nikolajewa, S. A New Classification Scheme of the Genetic Code. J Mol Evol 59, 598–605 (2004). https://doi.org/10.1007/s00239-004-2650-7

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00239-004-2650-7

Keywords

Navigation