Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Perspective
  • Published:

Physical non-equilibria for prebiotic nucleic acid chemistry

Nature Reviews Physics volume 5, pages 185–195 (2023)Cite this article

Subjects

Abstract

The prebiotic replication of DNA and RNA is a complex interplay between chemistry and the environment. Factors that have direct and indirect effects on prebiotic chemistry include temperature, concentration of monovalent and bivalent ions, the pH of water, ultraviolet irradiation and the presence of gaseous CO2. We discuss various primordial conditions to host the first replication reactions on the early Earth, including heated rock pores, hydrothermal vents, evaporating water ponds, freezing–thawing ice compartments, ultraviolet irradiation and high CO2 concentrations. We review how the interplay of replication chemistry with the strand separation and length selectivity of non-equilibrium physics can be provided by plausible geo-environments. Fast molecular evolution has been observed over a few hours in such settings when a polymerase protein is used as replicator. Such experimental findings make us optimistic that it will soon also be possible to probe evolution dynamics with much slower prebiotic replication chemistries using RNA. Our expectation is that the unique autonomous evolution dynamics provided by microfluidic non-equilibria make the origin of life understandable and experimentally testable in the near future.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Proposed primordial geological settings for fluctuations in temperature, salts and pH, ultraviolet irradiation and high CO2 concentrations.
Fig. 2: The chemico-physical determinants of oligonucleotide stability.
Fig. 3: Non-equilibrium environments to shape oligonucleotide evolution.
Fig. 4: Heterogeneous chemico-physical possibilities to drive the origin of life.

Similar content being viewed by others

References

  1. Mojzsis, S. J., Harrison, T. M. & Pidgeon, R. T. Oxygen-isotope evidence from ancient zircons for liquid water at the Earth’s surface 4,300 Myr ago. Nature 409, 178–181 (2001).

    Article  ADS  Google Scholar 

  2. Wilde, S. A., Valley, J. W., Peck, W. H. & Graham, C. M. Evidence from detrital zircons for the existence of continental crust and oceans on the Earth 4.4 Gyr ago. Nature 409, 175–178 (2001).

    Article  ADS  Google Scholar 

  3. Valley, J. W. et al. Hadean age for a post-magma-ocean zircon confirmed by atom-probe tomography. Nat. Geosci. 7, 219–223 (2014).

    Article  ADS  Google Scholar 

  4. Schrödinger, E. What is Life? The Physical Aspect of the Living Cell (Cambridge Univ. Press, 1944).

  5. Goldenfeld, N. & Woese, C. Life is physics: evolution as a collective phenomenon far from equilibrium. Annu. Rev. Condens. Mater. Phys. 2, 375–399 (2010).

    Article  ADS  Google Scholar 

  6. Michaelian, K. Thermodynamic dissipation theory for the origin of life. Earth Syst. Dyn. 2, 37–51 (2011).

    Article  ADS  Google Scholar 

  7. Marsh, M. G. E. Thermodynamics and the origin of life. Can. J. Phys. https://doi.org/10.1139/CJP-2020-0013 (2022).

    Article  Google Scholar 

  8. Barge, L. M. et al. Thermodynamics, disequilibrium, evolution: far-from-equilibrium geological and chemical considerations for origin-of-life research. Orig. Life Evol. Biosph. 47, 39–56 (2016).

    Article  ADS  Google Scholar 

  9. Ricker, G. R. et al. Transiting exoplanet survey satellite. J. Astron. Telesc. Instrum., Syst. 1, 014003 (2014).

    Article  ADS  Google Scholar 

  10. Borucki, W. J. et al. Kepler planet-detection mission: introduction and first results. Science 327, 977–980 (2010).

    Article  ADS  Google Scholar 

  11. Ávila, P. J. et al. Presence of water on exomoons orbiting free-floating planets: a case study. Int. J. Astrobiol. 20, 300–311 (2021).

    Article  ADS  Google Scholar 

  12. Damer, B. & Deamer, D. The hot spring hypothesis for an origin of life. Astrobiology 20, 429–452 (2020).

    Article  ADS  Google Scholar 

  13. Follmann, H. & Brownson, C. Darwin’s warm little pond revisited: from molecules to the origin of life. Naturwissenschaften 96, 1265–1292 (2009).

    Article  ADS  Google Scholar 

  14. Becker, S. et al. Wet-dry cycles enable the parallel origin of canonical and non-canonical nucleosides by continuous synthesis. Nat. Commun. 9, 163 (2018).

    Article  ADS  Google Scholar 

  15. Kim, H. J. & Benner, S. A. Prebiotic stereoselective synthesis of purine and noncanonical pyrimidine nucleotide from nucleobases and phosphorylated carbohydrates. Proc. Natl Acad. Sci. USA 114, 11315–11320 (2017).

    Article  ADS  Google Scholar 

  16. Okamura, H. et al. A one-pot, water compatible synthesis of pyrimidine nucleobases under plausible prebiotic conditions. Chem. Commun. 55, 1939–1942 (2019).

    Article  Google Scholar 

  17. Gull, M. Prebiotic phosphorylation reactions on the early earth. Challenges 5, 193–212 (2014).

    Article  ADS  Google Scholar 

  18. Orsythe, J. et al. Ester-mediated amide bond formation driven by wet–dry cycles: a possible path to polypeptides on the prebiotic Earth. Angew. Chem. Int. Ed. 54, 9871–9875 (2015).

    Article  Google Scholar 

  19. Mamajanov, I. et al. Ester formation and hydrolysis during wet-dry cycles: generation of far-from-equilibrium polymers in a model prebiotic reaction. Macromolecules 47, 1334–1343 (2014).

    Article  ADS  Google Scholar 

  20. Da Silva, L., Maurel, M. C. & Deamer, D. Salt-promoted synthesis of RNA-like molecules in simulated hydrothermal conditions. J. Mol. Evol. 80, 86–97 (2015).

    Article  ADS  Google Scholar 

  21. Morasch, M., Mast, C. B., Langer, J. K., Schilcher, P. & Braun, D. Dry polymerization of 3′,5′-cyclic GMP to long strands of RNA. ChemBioChem 15, 879–883 (2014).

    Article  Google Scholar 

  22. Roy, S., Bapat, N. V., Derr, J., Rajamani, S. & Sengupta, S. Emergence of ribozyme and tRNA-like structures from mineral-rich muddy pools on prebiotic Earth. J. Theor. Biol. 506, 110446 (2020).

    Article  MATH  Google Scholar 

  23. Pearce, B. K. D., Pudritz, R. E., Semenov, D. A. & Henning, T. K. Origin of the RNA world: the fate of nucleobases in warm little ponds. Proc. Natl Acad. Sci. USA 114, 11327–11332 (2017).

    Article  ADS  Google Scholar 

  24. Corliss, J. B., Baross, J. & Hoffman, S. An hypothesis concerning the relationships between submarine hot springs and the origin of life on Earth. Oceanol. Acta Special Issue 59–69 https://archimer.ifremer.fr/doc/00245/35661/ (1981).

  25. Russell, M. J., Daniel, R. M. & Hall, A. J. On the emergence of life via catalytic iron-sulphide membranes. Terra Nov. 5, 343–347 (1993).

    Article  ADS  Google Scholar 

  26. Martin, W. et al. On the origins of cells: a hypothesis for the evolutionary transitions from abiotic geochemistry to chemoautotrophic prokaryotes, and from prokaryotes to nucleated cells. Phil. Trans. R. Soc. Lond. B 358, 59–85 (2003).

    Article  Google Scholar 

  27. Martin, W. & Russell, M. J. On the origin of biochemistry at an alkaline hydrothermal vent. Phil. Trans. R. Soc. B 362, 1887–1926 (2007).

    Article  Google Scholar 

  28. Martin, W., Baross, J., Kelley, D. & Russell, M. J. Hydrothermal vents and the origin of life. Nat. Rev. Microbiol. 6, 805–814 (2008).

    Article  Google Scholar 

  29. Agerschou, E. D., Mast, C. B. & Braun, D. Emergence of life from trapped nucleotides? Non-equilibrium behavior of oligonucleotides in thermal gradients. Synlett 28, 56–63 (2017).

    Google Scholar 

  30. Baaske, P. et al. Extreme accumulation of nucleotides in simulated hydrothermal pore systems. Proc. Natl Acad. Sci. USA 104, 9346–9351 (2007).

    Article  ADS  Google Scholar 

  31. Mast, C. B. & Braun, D. Thermal trap for DNA replication. Phys. Rev. Lett. 104, 188102 (2010).

    Article  ADS  Google Scholar 

  32. Kreysing, M., Keil, L., Lanzmich, S. & Braun, D. Heat flux across an open pore enables the continuous replication and selection of oligonucleotides towards increasing length. Nat. Chem. 7, 203–208 (2015).

    Article  Google Scholar 

  33. Vallentyne, J. R. Biogeochemistry of organic matter — II Thermal reaction kinetics and transformation products of amino compounds. Geochim. Cosmochim. Acta 28, 157–188 (1964).

    Article  ADS  Google Scholar 

  34. Aubrey, A. D., Cleaves, H. J. & Bada, J. L. The role of submarine hydrothermal systems in the synthesis of amino acids. Orig. Life Evol. Biosph. 39, 91–108 (2009).

    Article  ADS  Google Scholar 

  35. Burcar, B. T. et al. RNA oligomerization in laboratory analogues of alkaline hydrothermal vent systems. Astrobiology 15, 509–522 (2015).

    Article  ADS  Google Scholar 

  36. Mast, C. B., Schink, S., Gerland, U. & Braun, D. Escalation of polymerization in a thermal gradient. Proc. Natl Acad. Sci. USA 110, 8030–8035 (2013).

    Article  ADS  Google Scholar 

  37. Braun, D., Goddard, N. L. & Libchaber, A. Exponential DNA replication by laminar convection. Phys. Rev. Lett. 91, 158103 (2003).

    Article  ADS  Google Scholar 

  38. White, R. H. Hydrolytic stability of biomolecules at high temperatures and its implication for life at 250 °C. Nature 310, 430–432 (1984).

    Article  ADS  Google Scholar 

  39. do Nascimento Vieira, A., Kleinermanns, K., Martin, W. F. & Preiner, M. The ambivalent role of water at the origins of life. FEBS Lett. 594, 2717–2733 (2020).

    Article  Google Scholar 

  40. Kadoya, S., Krissansen-Totton, J. & Catling, D. C. Probable cold and alkaline surface environment of the hadean Earth caused by impact ejecta weathering. Geochem. Geophys. Geosyst. 21, e2019GC008734 (2020).

    Article  ADS  Google Scholar 

  41. Zahnle, K., Schaefer, L. & Fegley, B. Earth’s earliest atmospheres. Cold Spring Harb. Perspect. Biol. 2, a004895 (2010).

    Article  Google Scholar 

  42. Trinks, H., Schröder, W. & Biebricher, C. K. Ice and the origin of life. Orig. Life Evol. Biosph. 35, 429–445 (2005).

    Article  ADS  Google Scholar 

  43. Bronshteyn, V. L. & Chernov, A. A. Freezing potentials arising on solidification of dilute aqueous solutions of electrolytes. J. Cryst. Growth 112, 129–145 (1991).

    Article  ADS  Google Scholar 

  44. Lohrmann, R. & Orgel, L. E. Template-directed reactions of aminonucleosides. J. Mol. Evol. 9, 323–328 (1977).

    Article  ADS  Google Scholar 

  45. Mutschler, H., Wochner, A. & Holliger, P. Freeze–thaw cycles as drivers of complex ribozyme assembly. Nat. Chem. 7, 502–508 (2015).

    Article  Google Scholar 

  46. Attwater, J., Wochner, A., Pinheiro, V. B., Coulson, A. & Holliger, P. Ice as a protocellular medium for RNA replication. Nat. Commun. 1, 76 (2010).

    Article  ADS  Google Scholar 

  47. Zhang, S. J., Duzdevich, D., Ding, D. & Szostak, J. W. Freeze–thaw cycles enable a prebiotically plausible and continuous pathway from nucleotide activation to nonenzymatic RNA copying. Proc. Natl Acad. Sci. USA 119, e2116429119 (2022).

    Article  Google Scholar 

  48. Ianeselli, A., Mast, C. B. & Braun, D. Periodic melting of oligonucleotides by oscillating salt concentrations triggered by microscale water cycles inside heated rock pores. Angew. Chem. Int. Ed. 58, 13155–13160 (2019).

    Article  Google Scholar 

  49. Morasch, M. et al. Heated gas bubbles enrich, crystallize, dry, phosphorylate and encapsulate prebiotic molecules. Nat. Chem. 11, 779–788 (2019).

    Article  Google Scholar 

  50. Lathe, R. Fast tidal cycling and the origin of life. Icarus 168, 18–22 (2004).

    Article  ADS  Google Scholar 

  51. Ianeselli, A. et al. Water cycles in a Hadean CO2 atmosphere drive the evolution of long DNA. Nat. Phys. 18, 579–585 (2022).

    Article  Google Scholar 

  52. Ianeselli, A. Hadean Water-dew Cycles Drive the Evolution of DNA and Protocells (Ludwig Maximilan Univ., 2022).

  53. Cleaves, H. J. et al. Mineral–organic interfacial processes: potential roles in the origins of life. Chem. Soc. Rev. 41, 5502–5525 (2012).

    Article  Google Scholar 

  54. Ricardo, A., Carrigan, M. A., Olcott, A. N. & Benner, S. A. Borate minerals stabilize ribose. Science 303, 196 (2004).

    Article  Google Scholar 

  55. Costanzo, G., Saladino, R., Crestini, C., Ciciriello, F. & Di Mauro, E. Nucleoside phosphorylation by phosphate minerals. J. Biol. Chem. 282, 16729–16735 (2007).

    Article  Google Scholar 

  56. Ferris, J. P., Hill, A. R., Liu, R. & Orgel, L. E. Synthesis of long prebiotic oligomers on mineral surfaces. Nature 381, 59–61 (1996).

    Article  ADS  Google Scholar 

  57. Ferris, J. P. Montmorillonite-catalysed formation of RNA oligomers: the possible role of catalysis in the origins of life. Philos. Trans. R. Soc. B Biol. Sci. 361, 1777 (2006).

    Article  Google Scholar 

  58. Gibbs, D., Lohrmann, R. & Orgel, L. E. Template-directed synthesis and selective adsorption of oligoadenylates on hydroxyapatite. J. Mol. Evol. 15, 347–354 (1980).

    Article  ADS  Google Scholar 

  59. Matreux, T. et al. Heat flows in rock cracks naturally optimize salt compositions for ribozymes. Nat. Chem. 13, 1038–1045 (2021).

    Article  Google Scholar 

  60. Namani, T. et al. Amino acid specific nonenzymatic montmorillonite-promoted RNA polymerization. ChemSystemsChem 3, e2000060 (2021).

    Article  Google Scholar 

  61. Jerome, C. A., Kim, H. J., Mojzsis, S. J., Benner, S. A. & Biondi, E. Catalytic synthesis of polyribonucleic acid on prebiotic rock glasses. Astrobiology 22, 629–636 (2022).

    Article  ADS  Google Scholar 

  62. Mizuuchi, R. et al. Mineral surfaces select for longer RNA molecules. Chem. Commun. 55, 2090–2093 (2019).

    Article  Google Scholar 

  63. Seibert, S. et al. Identification and quantification of redox and pH buffering processes in a heterogeneous, low carbonate aquifer during managed aquifer recharge. Water Resour. Res. 52, 4003–4025 (2016).

    Article  ADS  Google Scholar 

  64. Lacroix, E., Brovelli, A., Holliger, C. & Barry, D. A. Evaluation of silicate minerals for pH control during bioremediation: application to chlorinated solvents. Water Air Soil Pollut. 223, 2663–2684 (2012).

    Article  ADS  Google Scholar 

  65. Biondi, E., Branciamore, S., Maurel, M. C. & Gallori, E. Montmorillonite protection of an UV-irradiated hairpin ribozyme: evolution of the RNA world in a mineral environment. BMC Evol. Biol. 7, S2 (2007).

    Article  Google Scholar 

  66. Ranjan, S. & Sasselov, D. D. Constraints on the early terrestrial surface UV environment relevant to prebiotic chemistry. Astrobiology 17, 169–204 (2017).

    Article  ADS  Google Scholar 

  67. Crespo-Hernández, C. E. & Arce, R. Formamidopyrimidines as major products in the low- and high-intensity UV irradiation of guanine derivatives. J. Photochem. Photobiol. B 73, 167–175 (2004).

    Article  Google Scholar 

  68. Ranjan, S. et al. UV transmission in natural waters on prebiotic earth. Astrobiology 22, 242–262 (2022).

    ADS  Google Scholar 

  69. Boldissar, S. & De Vries, M. S. How nature covers its bases. Phys. Chem. Chem. Phys. 20, 9701–9716 (2018).

    Article  Google Scholar 

  70. De Vries, M. S. & Hobza, P. Gas-phase spectroscopy of biomolecular building blocks. Annu. Rev. Phys. Chem. 58, 585–612 (2007).

    Article  ADS  Google Scholar 

  71. Beckstead, A. A., Zhang, Y., De Vries, M. S. & Kohler, B. Life in the light: nucleic acid photoproperties as a legacy of chemical evolution. Phys. Chem. Chem. Phys. 18, 24228–24238 (2016).

    Article  Google Scholar 

  72. Todd, Z. R., Szabla, R., Szostak, J. W. & Sasselov, D. D. UV photostability of three 2-aminoazoles with key roles in prebiotic chemistry on the early earth. Chem. Commun. 55, 10388–10391 (2019).

    Article  Google Scholar 

  73. Todd, Z. R., Szostak, J. W. & Sasselov, D. D. Shielding from UV photodamage: implications for surficial origins of life chemistry on the early earth. ACS Earth Sp. Chem. 5, 239–246 (2021).

    Article  ADS  Google Scholar 

  74. Powner, M. W., Gerland, B. & Sutherland, J. D. Synthesis of activated pyrimidine ribonucleotides in prebiotically plausible conditions. Nature 459, 239–242 (2009).

    Article  ADS  Google Scholar 

  75. Rimmer, P. B. et al. The origin of RNA precursors on exoplanets. Sci. Adv. 4, eaar3302 (2018).

    Article  ADS  Google Scholar 

  76. Roberts, S. J. et al. Selective prebiotic conversion of pyrimidine and purine anhydronucleosides into Watson-Crick base-pairing arabino-furanosyl nucleosides in water. Nat. Commun. 9, 4073 (2018).

    Article  ADS  Google Scholar 

  77. Cnossen, I. et al. Habitat of early life: solar X-ray and UV radiation at Earth’s surface 4–3.5 billion years ago. J. Geophys. Res. Planets 112, 2008 (2007).

    Article  ADS  Google Scholar 

  78. Saladino, R. et al. Proton irradiation: a key to the challenge of N-glycosidic bond formation in a prebiotic context. Sci. Rep. 7, 14709 (2017).

    Article  ADS  Google Scholar 

  79. Baú, J. P. T. et al. Adenine adsorbed onto montmorillonite exposed to ionizing radiation: essays on prebiotic chemistry. Astrobiology 20, 26–38 (2020).

    Article  ADS  Google Scholar 

  80. Ebisuzaki, T. & Maruyama, S. Nuclear geyser model of the origin of life: driving force to promote the synthesis of building blocks of life. Geosci. Front. 8, 275–298 (2017).

    Article  Google Scholar 

  81. Miller, S. L. & Urey, H. C. Organic compound synthesis on the primitive earth. Science 130, 245–251 (1959).

    Article  ADS  Google Scholar 

  82. Pastorek, A. et al. Primordial radioactivity and prebiotic chemical evolution: effect of γ radiation on formamide-based synthesis. J. Phys. Chem. B 124, 8951–8959 (2020).

    Article  Google Scholar 

  83. Saladino, R. et al. Meteorite-catalyzed syntheses of nucleosides and of other prebiotic compounds from formamide under proton irradiation. Proc. Natl Acad. Sci. USA 112, E2746–E2755 (2015).

    Article  Google Scholar 

  84. Adam, Z. R., Fahrenbach, A. C., Jacobson, S. M., Kacar, B. & Zubarev, D. Y. Radiolysis generates a complex organosynthetic chemical network. Sci. Rep. 11, 1–10 (2021).

    Article  Google Scholar 

  85. Parke, W. C. Ionizing radiation and life. Biophysics https://doi.org/10.1007/978-3-030-44146-3_8 (2020).

    Article  Google Scholar 

  86. Baú, J. P. T. et al. Solid adenine and seawater salts exposed to gamma radiation: an FT-IR and EPR spectroscopy analysis for prebiotic chemistry. Heliyon 5, e01584 (2019).

    Article  Google Scholar 

  87. Kasting, J. F. Earth’s early atmosphere. Science 259, 920–926 (1993).

    Article  ADS  Google Scholar 

  88. Walker, J. C. G. Carbon dioxide on the early Earth. Orig. Life Evol. Biosph. 16, 117–127 (1985).

    Article  Google Scholar 

  89. Byck, H. T. Effect of dissolved CO2 on the pH of water. Science 75, 224 (1932).

    Article  ADS  Google Scholar 

  90. Al-Hindi, M. & Azizi, F. Absorption and desorption of carbon dioxide in several water types. Can. J. Chem. Eng. 96, 274–284 (2018).

    Article  Google Scholar 

  91. Wigley, T. M. L. & Brimblecombe, P. Carbon dioxide, ammonia and the origin of life. Nature 291, 213–215 (1981).

    Article  ADS  Google Scholar 

  92. Rimmer, P. B. & Shorttle, O. Origin of life’s building blocks in carbon-and nitrogen-rich surface hydrothermal vents. Life 9, 12 (2019).

    Article  Google Scholar 

  93. Feulner, G. The faint young Sun problem. Rev. Geophys. https://doi.org/10.1029/2011RG000375 (2012).

    Article  Google Scholar 

  94. Toner, J. D. & Catling, D. C. A carbonate-rich lake solution to the phosphate problem of the origin of life. Proc. Natl Acad. Sci. USA 117, 883–888 (2020).

    Article  ADS  Google Scholar 

  95. Donaldson, D. J., Tervahattu, H., Tuck, A. F. & Vaida, V. Organic aerosols and the origin of life: an hypothesis. Orig. Life Evol. Biosph. 34, 57–67 (2004).

    Article  ADS  Google Scholar 

  96. Ellison, G. B., Tuck, A. F. & Vaida, V. Atmospheric processing of organic aerosols. J. Geophys. Res. Atmos. 104, 11633–11641 (1999).

    Article  ADS  Google Scholar 

  97. Murphy, D. M., Thomson, D. S. & Mahoney, M. J. In situ measurements of organics, meteoritic material, mercury, and other elements in aerosols at 5 to 19 kilometers. Science 282, 1664–1669 (1998).

    Article  ADS  Google Scholar 

  98. Tuck, A. The role of atmospheric aerosols in the origin of life. Surv. Geophys. 23, 379–409 (2002).

    Article  ADS  Google Scholar 

  99. Trueblood, J. V. et al. The old and the new: aging of sea spray aerosol and formation of secondary marine aerosol through OH oxidation reactions. ACS Earth Sp. Chem. 3, 2307–2314 (2019).

    Article  ADS  Google Scholar 

  100. Griffith, E. C., Carpenter, B. K., Shoemaker, R. K. & Vaida, V. Photochemistry of aqueous pyruvic acid. Proc. Natl Acad. Sci. USA 110, 11714–11719 (2013).

    Article  ADS  Google Scholar 

  101. Dobson, C. M., Ellison, G. B., Tuck, A. F. & Vaida, V. Atmospheric aerosols as prebiotic chemical reactors. Proc. Natl Acad. Sci. USA 97, 11864–11868 (2000).

    Article  ADS  Google Scholar 

  102. Dora Tang, T. Y. et al. Fatty acid membrane assembly on coacervate microdroplets as a step towards a hybrid protocell model. Nat. Chem. 6, 527–533 (2014).

    Article  Google Scholar 

  103. Koga, S., Williams, D. S., Perriman, A. W. & Mann, S. Peptide–nucleotide microdroplets as a step towards a membrane-free protocell model. Nat. Chem. 3, 720–724 (2011).

    Article  Google Scholar 

  104. Tena-Solsona, M. et al. Kinetic control over droplet ripening in fuel-driven active emulsions. Preprint at https://doi.org/10.26434/CHEMRXIV.9978539.V1 (2019).

  105. Crosby, J. et al. Stabilization and enhanced reactivity of actinorhodin polyketide synthase minimal complex in polymer–nucleotide coacervate droplets. Chem. Commun. 48, 11832 (2012).

    Article  Google Scholar 

  106. Drobot, B. et al. Compartmentalised RNA catalysis in membrane-free coacervate protocells. Nat. Commun. 9, 3643 (2018).

    Article  ADS  Google Scholar 

  107. Poudyal, R. R. et al. Template-directed RNA polymerization and enhanced ribozyme catalysis inside membraneless compartments formed by coacervates. Nat. Commun. 10, 490 (2019).

    Article  ADS  Google Scholar 

  108. Priftis, D., Laugel, N. & Tirrell, M. Thermodynamic characterization of polypeptide complex coacervation. Langmuir 28, 15947–15957 (2012).

    Article  Google Scholar 

  109. Ianeselli, A. et al. Non-equilibrium conditions inside rock pores drive fission, maintenance and selection of coacervate protocells. Nat. Chem. 14, 32–39 (2021).

    Article  Google Scholar 

  110. Fialho, D. M., Roche, T. P. & Hud, N. V. Prebiotic syntheses of noncanonical nucleosides and nucleotides. Chem. Rev. 120, 4806–4830 (2020).

    Article  Google Scholar 

  111. Hud, N. V. Searching for lost nucleotides of the pre-RNA world with a self-refining model of early Earth. Nat. Commun. 9, 5171 (2018).

    Article  ADS  Google Scholar 

  112. Okamura, H. et al. Proto-Urea-RNA (Wöhler RNA) containing unusually stable urea nucleosides. Angew. Chem. Int. Ed. 58, 18691–18696 (2019).

    Article  Google Scholar 

  113. Müller, F. et al. A prebiotically plausible scenario of an RNA–peptide world. Nature 605, 279–284 (2022).

    Article  ADS  Google Scholar 

  114. Orgel, L. E. Prebiotic chemistry and the origin of the RNA world. Crit. Rev. Biochem. Mol. Biol. 39, 99–123 (2004).

    Article  Google Scholar 

  115. Alberts, B. et al. The RNA World and the Origins of Life. In Molecular Biology of the Cell 4th edn (Garland Science, 2002).

  116. Cojocaru, R. & Unrau, P. J. Transitioning to DNA genomes in an RNA world: the unexpected ability of an RNA polymerase ribozyme to copy RNA into DNA has ramifications for understanding how DNA genomes evolved. eLife 6, e32330 (2017).

    Article  Google Scholar 

  117. Xu, J., Green, N. J., Gibard, C., Krishnamurthy, R. & Sutherland, J. D. Prebiotic phosphorylation of 2-thiouridine provides either nucleotides or DNA building blocks via photoreduction. Nat. Chem. 11, 457–462 (2019).

    Article  Google Scholar 

  118. Szostak, J. W. The eightfold path to non-enzymatic RNA replication. J. Syst. Chem. 3, 2 (2012).

    Article  Google Scholar 

  119. Gruenwedel, D. W. & Hsu, C.-H. Salt effects on the denaturation of DNA. Biopolymers 7, 557–570 (1969).

    Article  Google Scholar 

  120. Bunville, L. G. & Geiduschek, E. P. DNA composition and stability to acid denaturation. Biochem. Biophys. Res. Commun. 2, 287–292 (1960).

    Article  Google Scholar 

  121. Thomas, R. The denaturation of DNA. Gene 135, 77–79 (1993).

    Article  Google Scholar 

  122. Göppel, T., Rosenberger, J. H., Altaner, B. & Gerland, U. Thermodynamic and kinetic sequence selection in enzyme-free polymer self-assembly inside a non-equilibrium RNA reactor. Life 12, 567 (2022).

    Article  Google Scholar 

  123. Nesbitt, S. M., Erlacher, H. A. & Fedor, M. J. The internal equilibrium of the hairpin ribozyme: temperature, ion and pH effects. J. Mol. Biol. 286, 1009–1024 (1999).

    Article  Google Scholar 

  124. Göppel, T., Obermayer, B., Chen, I. A. & Gerland, U. A kinetic error filtering mechanism for enzyme-free copying of nucleic acid sequences. bioRxiv https://doi.org/10.1101/2021.08.06.455386 (2021).

    Article  Google Scholar 

  125. Wada, A. & Suyama, A. Local stability of DNA and RNA secondary structure and its relation to biological functions. Proo. Biophys. molec. Biol. 47, 113–157 (1986).

    Article  Google Scholar 

  126. De Duve, C. The onset of selection. Nature 433, 581–582 (2005).

    Article  ADS  Google Scholar 

  127. Wachowius, F. & Holliger, P. Non-enzymatic assembly of a minimized RNA polymerase ribozyme. ChemSystemsChem 1, 1–4 (2019).

    Article  Google Scholar 

  128. Zhou, L., O’Flaherty, D. K. & Szostak, J. W. Assembly of a ribozyme ligase from short oligomers by nonenzymatic ligation. J. Am. Chem. Soc. 142, 15961–15965 (2020).

    Article  Google Scholar 

  129. Kudella, P. W., Tkachenko, A. V., Salditt, A., Maslov, S. & Braun, D. Structured sequences emerge from random pool when replicated by templated ligation. Proc. Natl Acad. Sci. USA 118, e2018830118 (2021).

    Article  Google Scholar 

  130. Ivica, N. A. et al. The paradox of dual roles in the RNA world: resolving the conflict between stable folding and templating ability. J. Mol. Evol. 77, 55–63 (2013).

    Article  ADS  Google Scholar 

  131. Cottrell, J. W., Scott, L. G. & Fedor, M. J. The pH dependence of hairpin ribozyme catalysis reflects ionization of an active site adenine. J. Biol. Chem. 286, 17658 (2011).

    Article  Google Scholar 

  132. Anella, F. & Danelon, C. Prebiotic factors influencing the activity of a ligase ribozyme. Life 7, 17 (2017).

    Article  Google Scholar 

  133. Peracchi, A. Origins of the temperature dependence of hammerhead ribozyme catalysis. Nucleic Acids Res. 27, 2875–2882 (1999).

    Article  Google Scholar 

  134. Wilson, T. J., Nahas, M., Ha, T. & Lilley, D. M. J. Folding and catalysis of the hairpin ribozyme. Biochem. Soc. Trans. 33, 461–465 (2005).

    Article  Google Scholar 

  135. Studier, F. W. Effects of the conformation of single-stranded DNA on renaturation and aggregation. J. Mol. Biol. 41, 199–209 (1969).

    Article  Google Scholar 

  136. Hinckley, D. M. et al. Coarse-grained modeling of DNA oligomer hybridization: length, sequence, and salt effects. J. Chem. Phys. 141, 035102 (2014).

    Article  ADS  Google Scholar 

  137. Tsuruoka, M. & Karube, I. Rapid hybridization at high salt concentration and detection of bacterial DNA using fluorescence polarization. Comb. Chem. High. Throughput Screen. 6, 225–234 (2003).

    Article  Google Scholar 

  138. Pörschke, D. & Eigen, M. Co-operative non-enzymic base recognition. 3. Kinetics of the helix-coil transition of the oligoribouridylic–oligoriboadenylic acid system and of oligoriboadenylic acid alone at acidic pH. J. Mol. Biol. 62, 361–381 (1971).

    Article  Google Scholar 

  139. Wong, K. L. & Liu, J. Factors and methods to modulate DNA hybridization kinetics. Biotechnol. J. 16, 2000338 (2021).

    Article  Google Scholar 

  140. Wetmur, J. G. & Davidson, N. Kinetics of renaturation of DNA. J. Mol. Biol. 31, 349–370 (1968).

    Article  Google Scholar 

  141. Kufner, C. L. et al. Sequence dependent UV damage of complete pools of oligonucleotides. bioRxiv https://doi.org/10.1101/2022.08.01.502267 (2022).

    Article  Google Scholar 

  142. Johns, H. E., Pearson, M. L., LeBlanc, J. C. & Helleiner, C. W. The ultraviolet photochemistry of thymidylyl-(3′→5′)-thymidine. J. Mol. Biol. 9, 503 (1964).

    Article  Google Scholar 

  143. Sugiyama, T., Keinard, B., Best, G. & Sanyal, M. R. Biochemical and photochemical mechanisms that produce different UV-induced mutation spectra. Mutat. Res. Mol. Mech. Mutagen. 823, 111762 (2021).

    Article  Google Scholar 

  144. Lemaire, D. G. E. & Ruzsicska, B. P. Quantum yields and secondary photoreactions of the photoproducts of dTpdT, dTpdC and dTpdU. Photochem. Photobiol. 57, 755–757 (1993).

    Article  Google Scholar 

  145. Kumar, S. et al. Adenine photodimerization in deoxyadenylate sequences: elucidation of the mechanism through structural studies of a major d(ApA) photoproduct. Nucleic Acids Res. 19, 2841–2847 (1991).

    Article  Google Scholar 

  146. Lee, J. H. et al. NMR structure of the DNA decamer duplex containing double T·G mismatches of cis–syn cyclobutane pyrimidine dimer: implications for DNA damage recognition by the XPC–hHR23B complex. Nucleic Acids Res. 32, 2474 (2004).

    Article  ADS  Google Scholar 

  147. Pilles, B. M. et al. Identification of charge separated states in thymine single strands. Chem. Commun. 50, 15623–15626 (2014).

    Article  Google Scholar 

  148. Bucher, D. B., Pilles, B. M., Carell, T. & Zinth, W. Dewar lesion formation in single- and double-stranded DNA is quenched by neighboring bases. J. Phys. Chem. B 119, 8685–8692 (2015).

    Article  Google Scholar 

  149. Kufner, C. L., Zinth, W. & Bucher, D. B. UV-induced charge-transfer states in short guanosine-containing DNA oligonucleotides. ChemBioChem 21, 2306–2310 (2020).

    Article  Google Scholar 

  150. Lu, C., Gutierrez-Bayona, N. E. & Taylor, J. S. The effect of flanking bases on direct and triplet sensitized cyclobutane pyrimidine dimer formation in DNA depends on the dipyrimidine, wavelength and the photosensitizer. Nucleic Acids Res. 49, 4266–4280 (2021).

    Article  Google Scholar 

  151. Bucher, D. B., Schlueter, A., Carell, T. & Zinth, W. Watson–Crick base pairing controls excited-state decay in natural DNA. Angew. Chem. Int. Ed. 53, 11366–11369 (2014).

    Article  Google Scholar 

  152. Saha, R. & Chen, I. A. Effect of UV radiation on fluorescent RNA aptamers’ functional and templating ability. ChemBioChem 20, 2609–2617 (2019).

    Article  Google Scholar 

  153. Kristoffersen, E. L., Burman, M., Noy, A. & Holliger, P. Rolling circle RNA synthesis catalysed by RNA. eLife 11, e75186. (2022).

    Article  Google Scholar 

  154. Tupper, A. S. & Higgs, P. G. Rolling-circle and strand-displacement mechanisms for non-enzymatic RNA replication at the time of the origin of life. J. Theor. Biol. 527, 110822 (2021).

    Article  MathSciNet  MATH  Google Scholar 

  155. Abels, J. A., Moreno-Herrero, F., Van Der Heijden, T., Dekker, C. & Dekker, N. H. Single-molecule measurements of the persistence length of double-stranded RNA. Biophys. J. 88, 2737 (2005).

    Article  Google Scholar 

  156. Zhou, L. et al. Non-enzymatic primer extension with strand displacement. eLife 8, e51888 (2019).

    Article  Google Scholar 

  157. Gavette, J. V. et al. RNA–DNA chimeras in the context of an RNA world transition to an RNA/DNA world. Angew. Chem. Int. Ed. 55, 13204–13209 (2016).

    Article  Google Scholar 

  158. Trevino, S. G., Zhang, N., Elenko, M. P., Lupták, A. & Szostak, J. W. Evolution of functional nucleic acids in the presence of nonheritable backbone heterogeneity. Proc. Natl Acad. Sci. USA 108, 13492–13497 (2011).

    Article  ADS  Google Scholar 

  159. Krishnamurthy, R. On the emergence of RNA. Isr. J. Chem. 55, 837–850 (2015).

    Article  Google Scholar 

  160. Hampel, A. & Cowan, J. A. A unique mechanism for RNA catalysis: the role of metal cofactors in hairpin ribozyme cleavage. Chem. Biol. 4, 513–517 (1997).

    Article  Google Scholar 

  161. Dass, A. V. et al. RNA oligomerisation without added catalyst from 2′,3′-cyclic nucleotides by drying at air-water interfaces. ChemSystChem https://doi.org/10.1002/syst.202200026 (2022).

    Article  Google Scholar 

  162. Altair, T., Borges, L. G. F., Galante, D. & Varela, H. Experimental approaches for testing the hypothesis of the emergence of life at submarine alkaline vents. Life 11, 777 (2021).

    Article  Google Scholar 

  163. Fox, S., Pleyer, H. L. & Strasdeit, H. An automated apparatus for the simulation of prebiotic wet–dry cycles under strictly anaerobic conditions. Int. J. Astrobiol. 18, 60–72 (2019).

    Article  ADS  Google Scholar 

  164. Vincent, L. et al. Chemical ecosystem selection on mineral surfaces reveals long-term dynamics consistent with the spontaneous emergence of mutual catalysis. Life 9, 80 (2019).

    Article  Google Scholar 

  165. Vincent, L. et al. The prebiotic kitchen: a guide to composing prebiotic soup recipes to test origins of life hypotheses. Life 11, 1221 (2021).

    Article  Google Scholar 

  166. Pearce, B. K. D., Molaverdikhani, K., Pudritz, R. E., Henning, T. & Cerrillo, K. E. Towards RNA life on early Earth: from atmospheric HCN to biomolecule production in warm little ponds. Astrophys. J. 932, 9 (2022).

    Article  ADS  Google Scholar 

  167. Salditt, A. et al. Thermal habitat for RNA amplification and accumulation. Phys. Rev. Lett. 125, 048104 (2020).

    Article  ADS  Google Scholar 

  168. Schroeder, R. Soups & SELEX for the origin of life. RNA 21, 729 (2015).

    Article  Google Scholar 

  169. Borsook, H. Peptide bond formation. Adv. Protein Chem. 8, 127–174 (1953).

    Article  Google Scholar 

  170. Kavdia, M. Phosphodiester bond formation. Encycl. Syst. Biol. https://doi.org/10.1007/978-1-4419-9863-7_1598 (2013).

    Article  Google Scholar 

  171. Walton, T., Zhang, W., Li, L., Tam, C. P. & Szostak, J. W. The mechanism of nonenzymatic template copying with imidazole-activated nucleotides. Angew. Chem. Int. Ed. 58, 10812–10819 (2019).

    Article  Google Scholar 

  172. Kaddour, H. & Sahai, N. Synergism and mutualism in non-enzymatic RNA polymerization. Life 4, 598–620 (2014).

    Article  Google Scholar 

  173. Blain, J. C., Ricardo, A. & Szostak, J. W. Synthesis and nonenzymatic template-directed polymerization of 2′-amino-2′-deoxythreose nucleotides. J. Am. Chem. Soc. 136, 2033–2039 (2014).

    Article  Google Scholar 

Download references

Acknowledgements

Financial support came from the European Research Council (ERC Evotrap, grant number 787356), the Simons Foundation (grant number 327125), the CRC 235 Emergence of Life (Project-ID 364653263), the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy — EXC-2094 — 390783311, and the Center for NanoScience (CeNS). Funding by the Volkswagen Initiative ‘Life? – A Fresh Scientific Approach to the Basic Principles of Life’ is gratefully acknowledged.

Author information

Author notes

  1. These authors contributed equally: Alan Ianeselli, Annalena Salditt, Christof Mast.

Authors and Affiliations

  1. Systems Biophysics, Center for Nanoscience, Ludwig-Maximilians-Universität München, Munich, Germany

    Alan Ianeselli, Annalena Salditt, Christof Mast & Dieter Braun

  2. Faculty of Computer Science, Free University of Bozen-Bolzano, Bolzano, Italy

    Alan Ianeselli

  3. University Observatory Munich, Ludwig-Maximilians-Universität München, München, Germany

    Barbara Ercolano

  4. Harvard-Smithsonian Center for Astrophysics, Department of Astronomy, Harvard University, Cambridge, MA, USA

    Corinna L. Kufner

  5. Earth and Environmental Sciences, Ludwig-Maximilians-Universität München, Munich, Germany

    Bettina Scheu

Authors
  1. Alan Ianeselli
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Annalena Salditt
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Christof Mast
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Barbara Ercolano
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Corinna L. Kufner
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Bettina Scheu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Dieter Braun
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

A.I., A.S., C.M., B.E., C.L.K., B.S. and D.B. structured the manuscript and wrote the text. A.I., A.S. and C.M. designed the figures and analysed the data.

Corresponding author

Correspondence to Dieter Braun.

Ethics declarations

Competing interests

The authors declare no competing interests.

Peer review

Peer review information

Nature Reviews Physics thanks Saúl Villafañe-Barajas, Philipp Holliger and the other, anonymous, referee(s) for their contribution to the peer review of this work.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ianeselli, A., Salditt, A., Mast, C. et al. Physical non-equilibria for prebiotic nucleic acid chemistry. Nat Rev Phys 5, 185–195 (2023). https://doi.org/10.1038/s42254-022-00550-3

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s42254-022-00550-3

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing