Abstract
The first living systems may have employed template-directed oligonucleotide ligation for replication. The utility of oligonucleotide ligation as a mechanism for the origin and evolution of life is in part dependent on its fidelity. We have devised a method for evaluating ligation fidelity in which ligation substrates are selected from random sequence libraries. The fidelities of chemical and enzymatic ligation are compared under a variety of conditions. While reaction conditions can be found that promote high fidelity copying, departure from these conditions leads to error-prone copying. In particular, ligation reactions with shorter oligonucleotide substrates are less efficient but more faithful. These results support a model for origins in which there was selective pressure for template-directed oligonucleotide ligation to be gradually supplanted by mononucleotide polymerization.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Achilles, T. and von Kiedrowski, G.: 1993, A self-replicating system from three starting materials. Angew. Chem. Int. Ed. Engl. 32, 1198–1201.
Bartel, D. P., Doudna, J. A., Usman, N. and Szostak, J.W.: 1991, Template-directed primer extension catalyzed by the Tetrahymena ribozyme. Mol. Cell. Biol. 11, 3390–3394.
Bartel, D. P. and Szostak, J. W.: 1993) Isolation of new ribozymes from a large pool of random sequences. Science 261, 1411–1418.
Been, M. D. and Cech, T. R.: 1988, RNA as an RNA polymerase: net elongation of an RNA primer catalyzed by the Tetrahymena ribozyme. Science 239, 1412–1416.
Benner, S. A., Ellington, A. D. and Tauer, A.: 1989, Modern metabolism as a palimpsest of the RNA world. Proc. Natl. Acad. Sci. U.S.A. 86, 7054–7058.
Bolli, M., Micura, R. and Eschenmoser, A.: 1997, Pyranosyl-RNA:chiroselective self-assembly of base sequences by ligative oligomerization of tetranucleotide-20, 30-cyclophosphates: with a commentary concerning the origin of biomolecular homochirality, Chem. Biol. 4, 309–320.
Bohler, C., Nielsen, P. E. and Orgel, L. E.: 1995, Template switching between PNA and RNA oligonucleotides. Nature 376, 578–581.
Carmi, N., Balkhi, S. R. and Breaker, R. R.: 1998, Cleaving DNA with DNA. Proc. Natl. Acad. Sci. USA 95, 2233–2237.
Ding, P. Z., Kawamura, K. and Ferris, J. P.: 1996, Oligomerization of uridine phosphorimidazolides on montmorillonite: a model for the prebiotic synthesis of RNA on minerals. Origin Life Evol. Biosph. 26, 151–171.
Ekland, E. H. and Bartel, D. P.: 1996, RNA-catalysed RNA polymerization using nucleoside triphosphates. Nature 382, 373–376.
Ekland, E. H., Szostak, J. W. and Bartel, D. P.: 1995, Structurally complex and highly active RNA ligases derived from random RNA sequences. Science 269, 364–370.
Ellington, A. D.: 1993, Experimental testing of theories of an early RNA world. Methods Enzymol 224, 646–664.
Ertem, G. and Ferris, J. P.: 1996, Synthesis of RNA oligomers on heterogeneous templates. Nature 379, 238–240.
Ferris, J. P., Hill, A. R., Liu, R. and Orgel, L. E.: 1996, Synthesis of long prebiotic oligomers on mineral surfaces. Nature 381, 59–61.
Gilbert, W.: 1986, The RNA world, Nature 319, 618.
James, K. D. and Ellington, A. D.: 1995, The search for missing links between self-replicating nucleic acids and the RNA world. Origins Life Evol. Biosph. 25, 515–530.
James, K. D. and Ellington, A. D.: 1997a, Catalysis and the RNA world in The Molecular Origins of Life A. Brack, ed. University of Cambridge Press, Cambridge (in press).
James, K. D. and Ellington, A. D.: 1997b, Surprising fidelity of template-directed, chemical ligation of oligonucleotides. Chem. Biol. 4, 595–610.
James, K. D. and Ellington, A. D.: 1998, The fidelity of template-directed oligonucleotide ligation and its relevance to DNA computation. Submitted to Nucl. Acids Res.
Joyce, G. F. et al.: 1984, Chiral selection in poly(C)-directed synthesis of oligo(G), Nature 310, 602–604.
Joyce, G. F.: 1989, RNA evolution and the origins of life. Nature 338, 217–224.
Joyce, G. F. and Orgel, L. E.: 1993, Prospects for understanding the origin of the RNA world in The RNA World, Gesteland, R. F. and Atkins, J. F., eds. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York. pp. 1–26.
Lee, D. H., Granja, J. R., Martinez, J. A., Severin, K. and Ghadiri, M. R.: 1996, A self-replicating peptide. Nature 382, 525–528.
Lee, D. H., Severin, K., Yokobayashi, Y. and Ghadiri, M. R.: 1997, Emergence of symbiosis in peptide self-replication through a hypercyclic network. Nature 390, 591–594.
Orgel, L. E.: 1992, Molecular replication. Nature 358, 203–209.
Pyle, A. M., Murphy, F. L. and Cech, T. R.: 1992, RNA substrate binding site in the catalytic core of the Tetrahymena ribozyme. Nature 358, 123–128.
Sabeti, P. C., Unrau, P. J. and Bartel, D. P.: 1997, Accessing rare activities from random RNA sequences: the importance of the length of molecules in the starting pool. Chem. Biol. 4, 767–774.
Schmidt, J. G., Nielsen, P. E. and Orgel, L. E.: 1997a, Information transfer from peptide nucleic acids to RNA by template-directed synthesis. Nucl. Acids Res. 25, 4797–4802.
Schmidt, J. G., Nielsen, P. E. and Orgel, L. E.: 1997b, Information transfer from DNA to peptide nucleic acids by template-directed synthesis. Nucl. Acids Res. 25, 4792–4796.
Schneider, K. C. and Benner, S. A.: 1990, Oligonucleotides containing flexible nucleoside analogs. J. Am. Chem. Soc. 112, 453–455.
Sharp, P. A.: 1985, On the origin of RNA splicing and introns. Cell 42, 397–400.
Sievers, D. and von Kiedrowski, G.: 1994, Self-replication of complementary nucleotide-based oligomers. Nature 369, 221–224.
Visscher, J. and Schwartz, A. W.: 1988, Template-directed synthesis of acyclic oligonucleotide analogues. J. Mol. Evol. 28, 3–6.
von Kiedrowski, G.: 1986, A self-replicating hexadeoxynucleotide. Angew. Chem. Int. Ed. Engl. 25, 932–935.
von Kiedrowski, G., Wlotzka, B., Helbing, J., Matzen, M. and Jordan, S.: 1991, Parabolic growth of a self-replicating hexadeoxynucleotide bearing a 30-50-phosphoamidate linkage. Angew. Chem. Int. Ed. Engl. 30, 423–426.
Zielinski, W. S. and Orgel, L. E.: 1987, Autocatalytic synthesis of a tetranucleotide analogue. Nature 327, 346–347.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
James, K.D., Ellington, A.D. The Fidelity of Template-Directed Oligonucleotide Ligation and the Inevitability of Polymerase Function. Orig Life Evol Biosph 29, 375–390 (1999). https://doi.org/10.1023/A:1006544611320
Issue Date:
DOI: https://doi.org/10.1023/A:1006544611320