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. 1978 Sep;75(9):4334–4338. doi: 10.1073/pnas.75.9.4334

Origin of the genetic code: a testable hypothesis based on tRNA structure, sequence, and kinetic proofreading.

J J Hopfield
PMCID: PMC336109  PMID: 279919

Abstract

We hypothesize that the origin of the genetic code is associated with the structure of the tRNA that existed in primal cells. The sequences of modern tRNA contain correlations which can be understood as "fossil" evidence of the secondary structure of primal tRNA. Kinetic proofreading through diffusion can amplify a low level of intrinsic selectivity of tRNA for its amino acid. Experimental tests of the theory are suggested.

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Selected References

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  1. Crick F. H., Brenner S., Klug A., Pieczenik G. A speculation on the origin of protein synthesis. Orig Life. 1976 Dec;7(4):389–397. doi: 10.1007/BF00927934. [DOI] [PubMed] [Google Scholar]
  2. Crick F. H. The origin of the genetic code. J Mol Biol. 1968 Dec;38(3):367–379. doi: 10.1016/0022-2836(68)90392-6. [DOI] [PubMed] [Google Scholar]
  3. Dunnill P. Triplet nucleotide-amino-acid pairing; a stereochemical basis for the division between protein and non-protein amino-acids. Nature. 1966 Jun 18;210(5042):1265–1267. doi: 10.1038/2101267a0. [DOI] [PubMed] [Google Scholar]
  4. Eigen M. Selforganization of matter and the evolution of biological macromolecules. Naturwissenschaften. 1971 Oct;58(10):465–523. doi: 10.1007/BF00623322. [DOI] [PubMed] [Google Scholar]
  5. Hopfield J. J. Kinetic proofreading: a new mechanism for reducing errors in biosynthetic processes requiring high specificity. Proc Natl Acad Sci U S A. 1974 Oct;71(10):4135–4139. doi: 10.1073/pnas.71.10.4135. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Hori H., Higo K., Osawa S. The rates of evolution in some ribosomal components. J Mol Evol. 1977 May 13;9(3):191–201. doi: 10.1007/BF01796108. [DOI] [PubMed] [Google Scholar]
  7. Ishida T., Sueoka N. Rearrangement of the secondary structure of the secondary structure of tryptophan sRNA in Escherichia coli. Proc Natl Acad Sci U S A. 1967 Sep;58(3):1080–1087. doi: 10.1073/pnas.58.3.1080. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Jordan B. R. Studies on 5 s RNA conformation by partial ribonuclease hydrolysis. J Mol Biol. 1971 Feb 14;55(3):423–439. doi: 10.1016/0022-2836(71)90327-5. [DOI] [PubMed] [Google Scholar]
  9. Jukes T. H. Possibilities for the evolution of the genetic code from a preceding form. Nature. 1973 Nov 2;246(5427):22–26. doi: 10.1038/246022a0. [DOI] [PubMed] [Google Scholar]
  10. Kim S. H., Sussman J. L., Suddath F. L., Quigley G. J., McPherson A., Wang A. H., Seeman N. C., RICH A. The general structure of transfer RNA molecules. Proc Natl Acad Sci U S A. 1974 Dec;71(12):4970–4974. doi: 10.1073/pnas.71.12.4970. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Lindahl T., Adams A., Fresco J. R. Renaturation of transfer ribonucleic acids through site binding of magnesium. Proc Natl Acad Sci U S A. 1966 Apr;55(4):941–948. doi: 10.1073/pnas.55.4.941. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Loftfield R. B. The mechanism of aminoacylation of transfer RNA. Prog Nucleic Acid Res Mol Biol. 1972;12:87–128. doi: 10.1016/s0079-6603(08)60660-1. [DOI] [PubMed] [Google Scholar]
  13. MILLER S. L., UREY H. C. Organic compound synthesis on the primitive earth. Science. 1959 Jul 31;130(3370):245–251. doi: 10.1126/science.130.3370.245. [DOI] [PubMed] [Google Scholar]
  14. Orgel L. E. Evolution of the genetic apparatus. J Mol Biol. 1968 Dec;38(3):381–393. doi: 10.1016/0022-2836(68)90393-8. [DOI] [PubMed] [Google Scholar]
  15. Pelc S. R., Welton M. G. Stereochemical relationship between coding triplets and amino-acids. Nature. 1966 Feb 26;209(5026):868–870. doi: 10.1038/209868a0. [DOI] [PubMed] [Google Scholar]
  16. Raszka M., Mandel M. Is there a physical chemical basis for the present genetic code? J Mol Evol. 1972 Dec 29;2(1):38–43. doi: 10.1007/BF01653941. [DOI] [PubMed] [Google Scholar]
  17. Ratner V. A., Batchinsky A. G. A cybernetic approach to the origin of the genetic coding mechanism. I. Methodological principles. Orig Life. 1976 Aug;7(3):225–228. doi: 10.1007/BF00926939. [DOI] [PubMed] [Google Scholar]
  18. Reanney D. C., Ralph R. K. A speculation on the origin of the genetic code. J Theor Biol. 1967 Apr;15(1):41–52. doi: 10.1016/0022-5193(67)90042-2. [DOI] [PubMed] [Google Scholar]
  19. Richards E. G., Lecanidou R., Geroch M. E. The kinetics of renaturation of 5-S RNA from Escherichia coli in the presence of Mg 2+ ions. Eur J Biochem. 1973 Apr;34(2):262–267. doi: 10.1111/j.1432-1033.1973.tb02755.x. [DOI] [PubMed] [Google Scholar]
  20. Robertus J. D., Ladner J. E., Finch J. T., Rhodes D., Brown R. S., Clark B. F., Klug A. Structure of yeast phenylalanine tRNA at 3 A resolution. Nature. 1974 Aug 16;250(467):546–551. doi: 10.1038/250546a0. [DOI] [PubMed] [Google Scholar]
  21. Saxinger C., Ponnamperuma C. Experimental investigation on the origin of the genetic code. J Mol Evol. 1971;1(1):63–73. doi: 10.1007/BF01659394. [DOI] [PubMed] [Google Scholar]
  22. Schwarz U., Menzel H. M., Gassen H. G. Codon-dependent rearrangement of the three-dimensional structure of phenylalanine tRNA, exposing the T-psi-C-G sequence for binding to the 50S ribosomal subunit. Biochemistry. 1976 Jun 1;15(11):2484–2490. doi: 10.1021/bi00656a035. [DOI] [PubMed] [Google Scholar]
  23. Spirin A. S. Cell-free systems of polypeptide biosynthesis and approaches to the evolution of translation apparatus. Orig Life. 1976 Apr;7(2):109–118. doi: 10.1007/BF00935655. [DOI] [PubMed] [Google Scholar]
  24. Weimann B. J., Lohrmann R., Orgel L. E., Schneider-Bernloehr H., Sulston J. E. Template-directed synthesis with adenosine-5'-phosphorimidazolide. Science. 1968 Jul 26;161(3839):387–387. doi: 10.1126/science.161.3839.387. [DOI] [PubMed] [Google Scholar]
  25. Woese C. R., Dugre D. H., Saxinger W. C., Dugre S. A. The molecular basis for the genetic code. Proc Natl Acad Sci U S A. 1966 Apr;55(4):966–974. doi: 10.1073/pnas.55.4.966. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Woese C. R. The fundamental nature of the genetic code: prebiotic interactions between polynucleotides and polyamino acids or their derivatives. Proc Natl Acad Sci U S A. 1968 Jan;59(1):110–117. doi: 10.1073/pnas.59.1.110. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Woese C. Models for the evolution of codon assignments. J Mol Biol. 1969 Jul 14;43(1):235–240. doi: 10.1016/0022-2836(69)90095-3. [DOI] [PubMed] [Google Scholar]
  28. Woese C. Molecular mechanics of translation: a reciprocating ratchet mechanism. Nature. 1970 May 30;226(5248):817–820. doi: 10.1038/226817a0. [DOI] [PubMed] [Google Scholar]
  29. Yoshida M., Kaziro Y., Ukita T. The modification of nucleosides and nucleotides. X. Evidence for the important role of inosine residue in codon recognition of yeast alanine tRNA. Biochim Biophys Acta. 1968 Oct 29;166(3):646–655. [PubMed] [Google Scholar]

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