Skip to main content
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1987 Jul;84(13):4398–4402. doi: 10.1073/pnas.84.13.4398

The case for an ancestral genetic system involving simple analogues of the nucleotides.

G F Joyce, A W Schwartz, S L Miller, L E Orgel
PMCID: PMC305096  PMID: 2440020

Abstract

The idea that the first living systems on earth were based on self-replicating RNA molecules has recently become popular as a result of the discovery of ribozymes. However, there are several major problems associated with the prebiotic synthesis of ribonucleotides. In addition, there is the newly recognized problem of enantiomeric cross-inhibition, whereby template-directed polymerization involving one enantiomer of RNA is inhibited strongly by the presence of the other enantiomer. Here we propose that RNA was preceded in the evolution of life by a polymer constructed from flexible, acyclic, probably prochiral nucleotide analogues that were synthesized readily on the primitive earth. Several potentially prebiotic nucleotide analogues are considered in this context, and some of the consequences of this proposal are discussed.

Full text

PDF

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bonner W. A. Experimental evidence for beta-decay as a source of chirality by enantiomer analysis. Orig Life. 1984;14(1-4):383–390. doi: 10.1007/BF00933681. [DOI] [PubMed] [Google Scholar]
  2. Cech T. R. A model for the RNA-catalyzed replication of RNA. Proc Natl Acad Sci U S A. 1986 Jun;83(12):4360–4363. doi: 10.1073/pnas.83.12.4360. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. 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]
  4. Darnell J. E., Doolittle W. F. Speculations on the early course of evolution. Proc Natl Acad Sci U S A. 1986 Mar;83(5):1271–1275. doi: 10.1073/pnas.83.5.1271. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Fuller W. D., Sanchez R. A., Orgel L. E. Studies in prebiotic synthesis: VII. Solid-state synthesis of purine nucleosides. J Mol Evol. 1972;1(3):249–257. doi: 10.1007/BF01660244. [DOI] [PubMed] [Google Scholar]
  6. Gabel N. W., Ponnamperuma C. Model for origin of monosaccharides. Nature. 1967 Nov 4;216(5114):453–455. doi: 10.1038/216453a0. [DOI] [PubMed] [Google Scholar]
  7. Gidley D. W., Rich A., Van House J., Zitzewitz P. W. beta Decay and the origins of biological chirality: experimental results. Nature. 1982 Jun 24;297(5868):639–643. doi: 10.1038/297639a0. [DOI] [PubMed] [Google Scholar]
  8. Guerrier-Takada C., Gardiner K., Marsh T., Pace N., Altman S. The RNA moiety of ribonuclease P is the catalytic subunit of the enzyme. Cell. 1983 Dec;35(3 Pt 2):849–857. doi: 10.1016/0092-8674(83)90117-4. [DOI] [PubMed] [Google Scholar]
  9. Guerrier-Takada C., Haydock K., Allen L., Altman S. Metal ion requirements and other aspects of the reaction catalyzed by M1 RNA, the RNA subunit of ribonuclease P from Escherichia coli. Biochemistry. 1986 Apr 8;25(7):1509–1515. doi: 10.1021/bi00355a006. [DOI] [PubMed] [Google Scholar]
  10. Hegstrom R. A., Rich A., Van House J. New estimates of asymmetric decomposition of racemic mixtures by natural beta-radiation sources. Nature. 1985 Jan 31;313:391–392. doi: 10.1038/313391a0. [DOI] [PubMed] [Google Scholar]
  11. Inoue T., Orgel L. E. Oligomerization of (guanosine 5'-phosphor)-2-methylimidazolide on poly(C). An RNA polymerase model. J Mol Biol. 1982 Nov 25;162(1):201–217. doi: 10.1016/0022-2836(82)90169-3. [DOI] [PubMed] [Google Scholar]
  12. Joyce G. F., Visser G. M., van Boeckel C. A., van Boom J. H., Orgel L. E., van Westrenen J. Chiral selection in poly(C)-directed synthesis of oligo(G). Nature. 1984 Aug 16;310(5978):602–604. doi: 10.1038/310602a0. [DOI] [PubMed] [Google Scholar]
  13. Lewin R. RNA Catalysis Gives Fresh Perspective on the Origin of Life: The old chicken-and-egg problem of the origin of life is illuminated in unexpected ways by recent results on the splicing of RNA precursors. Science. 1986 Feb 7;231(4738):545–546. doi: 10.1126/science.231.4738.545. [DOI] [PubMed] [Google Scholar]
  14. Morvan F., Rayner B., Imbach J. L., Chang D. K., Lown J. W. alpha-DNA. I. Synthesis, characterization by high field 1H-NMR, and base-pairing properties of the unnatural hexadeoxyribonucleotide alpha-[d(CpCpTpTpCpC)] with its complement beta-[d(GpGpApApGpG)]. Nucleic Acids Res. 1986 Jun 25;14(12):5019–5035. doi: 10.1093/nar/14.12.5019. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Nelsestuen G. L. Origin of life: consideration of alternatives to proteins and nucleic acids. J Mol Evol. 1980 Mar;15(1):59–72. doi: 10.1007/BF01732583. [DOI] [PubMed] [Google Scholar]
  16. Orgel L. E. Did template-directed nucleation precede molecular replication? Orig Life Evol Biosph. 1986;17(1):27–34. doi: 10.1007/BF01809810. [DOI] [PubMed] [Google Scholar]
  17. 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]
  18. Reid C., Orgel L. E. Synthesis in sugars in potentially prebiotic conditions. Nature. 1967 Nov 4;216(5114):455–455. doi: 10.1038/216455a0. [DOI] [PubMed] [Google Scholar]
  19. Sanchez R. A., Orgel L. E. Studies in prebiotic synthesis. V. Synthesis and photoanomerization of pyrimidine nucleosides. J Mol Biol. 1970 Feb 14;47(3):531–543. doi: 10.1016/0022-2836(70)90320-7. [DOI] [PubMed] [Google Scholar]
  20. Schwartz A. W., Orgel L. E. Template-directed synthesis of novel, nucleic acid-like structures. Science. 1985 May 3;228:585–587. doi: 10.1126/science.228.4699.585. [DOI] [PubMed] [Google Scholar]
  21. Spach G. Chiral versus chemical evolutions and the appearance of life. Orig Life. 1984;14(1-4):433–437. doi: 10.1007/BF00933688. [DOI] [PubMed] [Google Scholar]
  22. Van Trump J. E., Miller S. L. Prebiotic synthesis of methionine. Science. 1972 Nov 24;178(4063):859–860. doi: 10.1126/science.178.4063.859. [DOI] [PubMed] [Google Scholar]
  23. Westheimer F. H. Polyribonucleic acids as enzymes. Nature. 1986 Feb 13;319(6054):534–535. doi: 10.1038/319534a0. [DOI] [PubMed] [Google Scholar]
  24. Zaug A. J., Cech T. R. The intervening sequence RNA of Tetrahymena is an enzyme. Science. 1986 Jan 31;231(4737):470–475. doi: 10.1126/science.3941911. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES