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A Stochastic Model of Nonenzymatic Nucleic Acid Replication: “Elongators” Sequester Replicators

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Abstract

The origin of nucleic acid template replication is a major unsolved problem in science. A novel stochastic model of nucleic acid chemistry was developed to allow rapid prototyping of chemical experiments designed to discover sufficient conditions for template replication. Experiments using the model brought to attention a robust property of nucleic acid template populations, the tendency for elongation to outcompete replication. Externally imposed denaturation-renaturation cycles did not reverse this tendency. For example, it has been proposed that fast tidal cycling could establish a TCR (tidal chain reaction) analogous to a PCR (polymerase chain reaction) acting on nucleic acid polymers, allowing their self-replication. However, elongating side-reactions that would have been prevented by the polymerase in the PCR still occurred in the simulation of the TCR. The same finding was found with temperature and monomer cycles. We propose that if cycling reactors are to allow template replication, oligonucleotide phenotypes that are capable of favorably altering the flux ratio between replication and elongation, for example, by facilitating sequence-specific cleavage within templates, are necessary; accordingly the minimal replicase ribozyme may have possessed restriction functionality.

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Notes

  1. Avogadro’s number × Volume is defined as 10,000. Dividing the number of molecules by this value gives the concentration as moles per liter.

  2. The rules are applied to the system using a variant of the SSA algorithm (Elf and Ehrenburg 2004), based on the next reaction method of the Gillespie algorithm (Gillespie 1977; Gibson and Bruck 2000).

  3. These are codes for the classes of equivalent h-bond neighborhood states that contribute the same stacking stability to the central h-bond. They label the 16 configurations shown in Fig. 4 rule 1.

  4. We model a replicase ribozyme that behaves similarly to the sequence-nonspecific RNA-dependent RNA polymerase protein enzyme from Q beta.

  5. Elongation is observed even in the absence of spontaneous ligation if the system is initialized with 10-mers.

  6. Sequence-independent degradation reactions are insufficient because they would result in stochastic loss of sequence information.

References

  • Braun D, Libchaber A (2004) Thermal force approach to molecular evolution. Phys Biol 1:1–8

    Article  CAS  Google Scholar 

  • Breivik J (2001) Self-organization of template-replicating polymers and the spontaneous rise of genetic information. Entropy 3:273–279

    Article  CAS  Google Scholar 

  • Cantor CR, Schimmel PR (1980) Statistical mechanics and kinetics of nucleic acid interactions. In: Biophysical chemistry. W. H Freeman, San Fransisco, pp 1183–1264

  • Cech TR (2002) Ribozyme, the first 20 years. Biochem Soc Trans 30:1162–1166

    Article  PubMed  CAS  Google Scholar 

  • Cruz P, Bubienko E, Borer P (1982) A model for base overlap in RNA. Nature 298:198–200

    Article  PubMed  CAS  Google Scholar 

  • Elf J, Ehrenberg M (2004) Spontaneous seperation of bi-stable biochemical systems into spatial domains of opposite phases. IEE Syst Biol 1(2):230–236

    CAS  Google Scholar 

  • Ferris JP, Hill AR Jr, Liu R, Orgel LE (1996) Synthesis of long prebiotic oligomers on mineral surfaces. Nature 381:59–61

    Article  PubMed  CAS  Google Scholar 

  • Fernando CT, Di Paolo E (2004) A model for the origin of long RNA templates. In: Proceedings of the Ninth International Conference of Artificial Life, Boston, MA, pp 1–9

  • Gánti T (1979) A theory of biochemical supersystems and its application to problems of natural and artifical biogenesis. Akadémiai Kiadó, Budapest/University Park Press, Baltimore

    Google Scholar 

  • Gánti T (2003) The principles of life. Oxford University Press, Oxford

    Google Scholar 

  • Gibson A, Bruck G (2000) Efficient exact stochastic simulation of chemical systems with many species and many channels. J Phys Chem A 104:1876–1889

    Article  CAS  Google Scholar 

  • Gilbert W (1986) The RNA world. Nature 319:618

    Article  Google Scholar 

  • Gillespie D (1977) Exact stochastic simulation of coupled chemical reactions. J Phys Chem 8:2340–2381

    Article  Google Scholar 

  • Griffith S, Goldwater D, Jacobson JM (2005) Robotics: self-replication from random parts. Nature 437:636

    Article  PubMed  CAS  Google Scholar 

  • Jeffries AC, Symons RH (1989) A catalytic 13-mer ribozyme. Nucleic Acids Res 17:1371–1377

    Article  PubMed  CAS  Google Scholar 

  • Johnston WK, Unrau PJ, Lawrence MS, Glasner ME, Bartel DP (2001) RNA-catalyzed RNA polymerization: accurate and general RNA-templated primer extension. Science 292:1319–1325

    Article  PubMed  CAS  Google Scholar 

  • Kanavarioti A (1994) Template-directed chemistry and the origins of the RNA world. Origins Life Evol Biosph 24:479–495

    Article  CAS  Google Scholar 

  • Kanavarioti A, Bemasconi C (1990) Computer simulation in template-directed oligonucleotide synthesis. J Mol Evol 31:470–477

    Article  PubMed  CAS  Google Scholar 

  • Kovac L, Nosek J, Tomaska L (2003) An overlooked riddle of life’s origins: energy-dependent nucleic acid unzipping. J Mol Evol 57:S182—S189

    Article  PubMed  CAS  Google Scholar 

  • Kuhn H (1972) Selbstorganisation molekularer Systeme und die Evolution des genetischen Apparats. Angew Chem 84:838–862

    Google Scholar 

  • Lathe R (2003) Fast tidal cycling and the origin of life. Icarus 168:18–22

    Article  CAS  Google Scholar 

  • Lathe R (2005) Tidal chain reaction and the origin of replicating biopolymers. Int J Astrobiol 4(1):19–31

    Article  CAS  Google Scholar 

  • Maynard Smith J, Szathmáry E (1995) The major transitions in evolution. Oxford University Press, Oxford

    Google Scholar 

  • Reynaldo LP, Vologodskii V, Neri BP, Lyamichev VI (2000) The kinetics of oligonucleotide replacements. J Mol Biol 297:511–520

    Article  PubMed  CAS  Google Scholar 

  • Rohatgi R, Bartel DP, Szostak JK (1996) Nonenzymatic, template-directed ligation of oligoribonucleotides is highly regioselective for the formation of 3′–5′ phosphodiester bonds. J Am Chem Soc 118:3340–3344

    Article  PubMed  CAS  Google Scholar 

  • SantaLucia J (1998) A unified view of polymer, dumbell, and oligonucleotide DNA nearest-neighbor thermodynamics. Proc Natl Acad Sci USA 95:1460–1465

    Article  PubMed  CAS  Google Scholar 

  • Schoneborn H, Bulle J, Von Kiedrowski G (2001) Kinetic monitoring of self-replicating systems through measurement of flourescence resonance energy transfer. Chembiochem 12:922–927

    Article  Google Scholar 

  • Sievers D, Von Kiedrowski G (1994) Self-replication of complementary nucleotide-based oligomers. Nature 369:221–224

    Article  PubMed  CAS  Google Scholar 

  • Sinclair A, Alkema D, Bell RA, Coddington JM, Hughes DW, Neilson T, Romaniuk PJ (1984) Relative stability of guanosine-cytidine diribonucleotide cores: a h-NMR assessment. Biochemistry 23:2656–2662

    Article  PubMed  CAS  Google Scholar 

  • Stein DL, Anderson PW (1984) A model for the origin of biological catalysis. Proc Natl Acad Sci USA 81(6):1751–1753

    Article  PubMed  CAS  Google Scholar 

  • Szathmáry E, Maynard Smith J (1997) From replicators to reproducers: the first major transitions leading to life. J Theor Biol 187:555–571

    Article  PubMed  Google Scholar 

  • Szathmáry E, Santos M, Fernando C (2005) Evolutionary potential and requirements for minimal protocells. Topics Curr Chem 259:167–211

    Article  CAS  Google Scholar 

  • Turner DH (2000) Conformational changes. In: Bloomfield VA, Crothers DM, Tinoco I Jr (eds) Nucleic acids: structures, properties and functions. University Science Press

  • Verga P, Rybicki C, Davis KR (2006) Comment on the paper “Fast Tidal Cycling and the Origin of Life” by Richard Lathe. Icarus 180(1):274–276

    Article  CAS  Google Scholar 

  • Von Kiedrowski G (1986) A self-replicating hexadeoxynucleotide. Angew Chem Int Ed Engl 25:932–934

    Article  Google Scholar 

  • Von Kiedrowski G (1993) Minimal replicator theory i: parabolic versus exponential growth. Bioorg Chem Front 3:113–146

    Google Scholar 

  • Wattis J, Coveney P (1999) The origin of the RNA world: a kinetic model. J Phys Chem B 103:4231–4250

    Article  CAS  Google Scholar 

  • Wills P, Kauffman S, Stadler B, Stadler P (1998) Selection dynamics in autocatalytic systems: templates replicating through binary ligation. Bull Math Biol 1:1–26

    Google Scholar 

  • Xia T, SantaLucia J, Kierzek R, Schroeder R, Cox C, Turner D (1998) Thermodynamic parameters for an expanded nearest-neighbor model for formation of RNA duplexes with Watson-Crick base pairs. Biochemistry 37:14719–14735

    Article  PubMed  CAS  Google Scholar 

  • Zielinski W, Orgel L (1987a) Autocatalytic synthesis of a tetranucleotide analogue. Nature 327:346–437

    Article  CAS  Google Scholar 

  • Zielinski W, Orgel L (1987b) Oligoaminonucleoside phosphoramidates. Oligomerization of dimers of 3′-amino-3-deoxynucleotides (GC and CG) in aqueous solution. Nucleic Acids Res 15:1699–1715

    Article  CAS  Google Scholar 

  • Zielinski W, Orgel L (1989) The template properties of triphosphraamidates having CG residues. J Mol Evol 29:281–283

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was partly supported by the Hungarian National Research Fund (OTKA T047245), the National Office for Research and Technology (NAP 2005/ KCKHA005) of Hungary, and the ESIGNET European 6th Framework Grant for Cell Signalling Networks. Thanks go to Johan Elf, Mans Ehrenberg, and Simon McGregor for help with the writing of the code for the stochastic algorithm and design of the two-timescale method. Thanks are due to Richard Lathe for helpful comments during the preparation of the manuscript.

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Authors and Affiliations

  1. School of Computer Science, University of Birmingham, Edgbaston, B15 2TT, UK

    Chrisantha Fernando

  2. Collegium Budapest (Institute for Advanced Study), Szentháromság u. 2, H-1014, Budapest, Hungary

    Chrisantha Fernando & Eörs Szathmáry

  3. Center for Computational Neuroscience and Robotics, University of Sussex, Brighton, BN1 9RH, UK

    Chrisantha Fernando

  4. Bioorganische Chemie, Lehrstuhl für Organische Chemie I, Faculty of Chemistry, Ruhr Universität Bochum, Universitätsstr.150, 44780, Bochum, Germany

    Günter Von Kiedrowski

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  1. Chrisantha Fernando
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  2. Günter Von Kiedrowski
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  3. Eörs Szathmáry
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Correspondence to Chrisantha Fernando.

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Reviewing Editor: Dr. Niles Lehman

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Fernando, C., Von Kiedrowski, G. & Szathmáry, E. A Stochastic Model of Nonenzymatic Nucleic Acid Replication: “Elongators” Sequester Replicators. J Mol Evol 64, 572–585 (2007). https://doi.org/10.1007/s00239-006-0218-4

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  • DOI: https://doi.org/10.1007/s00239-006-0218-4

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