Abstract
Self-replicating chemical systems have been designed and studied to identify the minimal requirements for molecular replication1, to translate the principle into synthetic supramolecular systems2 and to derive a better understanding of the scope and limitations of self-organization processes3 that are believed to be relevant to the origin of life on Earth4. Current implementations make useofoligonucleotide analogues5,6,7,8,9,10,11,12, peptides13,14,15,16,17, and other molecules18,19,20,21,22,23,24 as templates and are based either on autocatalytic, cross-catalytic, or collectively catalytic pathways for template formation. A common problem of these systems is product inhibion, leading to parabolic instead of exponential amplification25. The latter is the dynamic prerequisite for selection in the darwinian sense26,27. We here describe an iterative, stepwise procedure for chemical replication which permits an exponential increase in the concentration of oligonucleotide analogues. The procedure employs the surface of a solid support and is called SPREAD (surface-promoted replication and exponential amplification of DNA analogues). Copies are synthesized from precursor fragments by chemical ligation on immobilized templates, and then liberated and immobilized to become new templates. The process is repeated iteratively. The role of the support is to separate complementary templates which would form stable duplexes in solution. SPREAD combines the advantages of solid-phase chemistry with chemical replication, and can be further developed for the non-enzymatic and enzymatic amplification of RNA, peptides and other templates as well as for studies of in vitro evolution and competition in artificial chemical systems. Similar processes may also have played a role in the origin of life on Earth, because the earliest replication systems may have proliferated by spreading on mineral surfaces28,29,30,31,32,33.
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References
Sievers, D. et al. Self-Reproduction of Supramolecular Structures—From Synthetic Structures to Models of Minimal Living Systems 45–64 (Kluwer, Dordrecht, 1994).
Wintner, E. A., Conn, M. M. & Rebek, J. Studies in molecular replication. Acc. Chem. Res. 27, 198–203 (1994).
Eigen, M. Selforganization of matter and the evolution of biological macromolecules. Naturwissenschaften 58, 465–523 (1971).
Orgel, L. E. Unnatural selection in chemical systems. Acc. Chem. Res. 28, 109–118 (1995).
von Kiedrowski, G. Aself-replicating hexadeoxynucleotide. Angew. Chem. Int. Edn Engl. 25, 932–935 (1986).
Zielinski, W. S. & Orgel, L. E. Autocatalytic synthesis of a tetranucleotide analogue. Nature 327, 346–347 (1987).
von Kiedrowski, G., Wlotzka, B., Helbing, J., Matzen, M. & Jordan, S. Parabolic growth of a hexadeoxynucleotide analogue bearing a 3′-5′-phosphoamidate link. Angew. Chem. Int. Edn Engl. 30, 423–426, 892 (1991).
Achilles, T. & von Kiedrowski, G. Aself-replicating system from three precursors. Angew. Chem. Int. Edn Engl. 32, 1198–1201 (1993).
Sievers, D. & von Kiedrowski, G. Self-replication of complementary nucleotide-based oligomers. Nature 369, 221–224 (1994).
Li, T. & Nicolaou, K. C. Chemical self-replication of palindromic duplex DNA. Nature 369, 218–221 (1994).
Martin, B., Micura, R., Pitsch, S. & Eschenmoser, A. Pyranosyl-RNA: further observations on replication. Helv. Chim. Acta 80, 1901–1951 (1997).
Sievers, D. & von Kiedrowski, G. Self-replication of hexadeoxynucleotide analogues: autocatalysis versus cross-catalysis. Chem. Eur. J. 4, 629–641 (1998).
Lee, D. H., Granja, J. R., Martinez, J. A., Severin, K. & Ghadiri, M. R. Aself-replicating peptide. Nature 382, 525–528 (1996).
Severin, K., Lee, D. H., Martinez, J. A., Vieth, M. & Ghadiri, M. R. Dynamic error correction in autocatalytic peptide networks. Angew. Chem. Int. Edn Engl. 37, 126–128 (1998).
Lee, D. H., Severin, K., Yokobayashi, Y. & Ghadiri, M. R. Emergence of symbiosis in peptide self-replication through a hypercyclic network. Nature 390, 591–594 (1997).
Yao, S., Ghosh, I., Zutshi, R. & Chmielewski, J. Aself-replicating peptide under ionic control. Angew. Chem. Int. Edn Engl. 37, 478–481 (1998).
Severin, K. S., Lee, D. H., Martinez, J. A. & Ghadiri, M. R. Peptide self-replication via template-directed ligation. Chem. Eur. J. 3, 1017–1024 (1997).
Tjivikua, T., Ballester, P. & Rebek, J. Aself-replicating system. J. Am. Chem. Soc. 112, 1249–1250 (1990).
Terfort, A. & von Kiedrowski, G. Self-replication during condensation of 3-aminobenzamidines with 2-formylphenoxyacetic acids. Angew. Chem. Int. Edn Engl. 31, 654–656 (1992).
Hong, J.-I., Feng, Q., Rotello, V. & Rebek, J. Competition, cooperation, and mutation: improving a synthetic replicator by light irradiation. Science 255, 848–850 (1992).
Feng, Q., Park, T. K. & Rebek, J. Crossover reactions between synthetic replicators yield active and inactive recombinants. Science 256, 1179–1180 (1992).
Pieters, R. J., Huc, I. & Rebek, J. Reciprocal template effect in a replication cycle. Angew. Chem. Int. Edn Engl. 106, 1579–1581 (1994).
Reinhoudt, D. N., Rudkevich, D. M. & de Jong, F. Kinetic analysis of the Rebek self-replicating system: is there a controversy? J. Am. Chem. Soc. 118, 6880–6889 (1996).
Wang, B. & Sutherland, I. O. Self-replication in a Diels-Alder reaction. Chem. Commun. 16, 1495–1496 (1997).
von Kiedrowski, G. Minimal replicator theory I: parabolic versus exponential growth. Bioorg. Chem. Front. 3, 113–146 (1993).
Szathmáry, E. & Gladkih, I. Sub-exponential growth and coexistence of non-enzymatically replicating templates. J. Theor. Biol. 138, 55–58 (1989).
Wills, R. W., Kauffman, S. A., Stadler, B. M. R. & Stadler, P. F. Selection Dynamics in Autocatalytic System: Templates Replicating Through Binary Ligation (Working Paper 97-07-065, Santa Fe Institute, 1997); also as Bull. Math. Biol. (in the press).
Bernal, J. D. The Physical Base of Life (Routledge & Kegan Paul, London, 1951).
Cairns-Smith, A. G. The Life Puzzle (Oliver & Boyd, Edinburgh, 1971).
Kuhn, H., Waser, J. Molecular self-organization and the origin of life. Angew. Chem. Int. Edn Engl. 20, 500–520 (1981).
Wächtershäuser, G. Before enzymes and templates: theory of surface metabolism. Microbiol. Rev. 52, 452–484 (1988).
Szathmary, E. & Smith, J. M. From replicators to reproducers: The first major transitions leading to life. J. Theor. Biol. 187, 555–571 (1997).
Orgel, L. E. Polymerization on the rocks: Theoretical introduction. Origins Life Evol. Biosphere 28, 227–234 (1998).
Ferris, J. P., Hill, A. R., Liu, R. & Orgel, L. E. Synthesis of long prebiotic oligomers on mineral surfaces. Nature 381, 59–61 (1996).
von Kiedrowski, G. Primordial soup or crêpes? Nature 381, 20–21 (1996).
Lorsch, J. R. & Szostak, W. J. In vitro evolution of new ribozymes with polynucleotide kinase activity. Nature 371, 31–36 (1994).
Dolinnaya, N. G., Tsytovish, A. V., Sergeev, V. N., Oretskaya, T. S. & Shabarova, Z. A. Structural and kinetic aspects of chemical reactions in DNA duplexes. Information on DNA local structure obtained from chemical ligation data. Nucleic Acids Res. 19, 3073–3080 (1991).
James, K. D. & Ellington, A. D. Surprising fidelity of template-directed chemical ligation of oligonucleotides. Chem. Biol. 4, 595–605 (1997).
Klussmann, S., Nolte, A., Bald, R., Erdmann, V. A. & Furste, J. P. Mirror-image RNA that binds D-adenosine. Nature Biotechnol. 14, 1112–1115 (1996).
Joyce, G. F. Origins of Life: The Central Conceptsforeword (Jones and Bartlett, Boston, 1994).
Acknowledgements
This work was supported by Deutsche Forschungsgemeinschaft (SFB 452), Fonds der Chemischen Industrie, German Israeli Foundation (GIF) and Bundesministerium für Bildung und Forschung (BMBF). We thank B. Materne and M. Wüstefeld for technical assistance, B. Kind for mathematical advice, and K. Johnsson and M. Zielinski for comments and suggestions on the manuscript.
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Luther, A., Brandsch, R. & von Kiedrowski, G. Surface-promoted replication and exponential amplification of DNA analogues. Nature 396, 245–248 (1998). https://doi.org/10.1038/24343
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DOI: https://doi.org/10.1038/24343
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