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The RNA World: molecular cooperation at the origins of life

Key Points

  • Research into the RNA World paradigm is active, and new discoveries in synthetic organic chemistry and biochemistry routinely provide new insights.

  • The field of prebiotic chemistry is increasingly discovering phenomena that provide solutions to multiple (as opposed to single) problems simultaneously.

  • A key issue in RNA World research is how RNAs might have made copies of themselves (that is, how they replicated). There are now several possible mechanisms of this process, and increasing focus is being placed on those that display autocatalytic feedback.

  • Cooperation among various molecules was probably a key aspect of the RNA World, and at least three types of molecular cooperation could have been at play during the origins of life.

  • Chemical alternatives to RNA per se may have existed at some point in the Earth's earliest history, and many efforts are underway to find and evaluate such structures.

  • Network establishment was another process that had a large impact on the organization of the living state, from small molecules to large molecules and cell-like structures.

Abstract

The RNA World concept posits that there was a period of time in primitive Earth's history — about 4 billion years ago — when the primary living substance was RNA or something chemically similar. In the past 50 years, this idea has gone from speculation to a prevailing idea. In this Review, we summarize the key logic behind the RNA World and describe some of the most important recent advances that have been made to support and expand this logic. We also discuss the ways in which molecular cooperation involving RNAs would facilitate the emergence and early evolution of life. The immediate future of RNA World research should be a very dynamic one.

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Figure 1: Research in different fields is coming together to assemble a more complete picture of the way the RNA World began and operated.
Figure 2: RNA polymerases as altruistic cooperators.
Figure 3: Different senses of molecular cooperation.

References

  1. Crick, F. H. C. The origin of the genetic code. J. Mol. Biol. 38, 367–379 (1968).

    Article  CAS  PubMed  Google Scholar 

  2. Orgel, L. E. Evolution of the genetic apparatus. J. Mol. Biol. 38, 381–393 (1968).

    Article  CAS  PubMed  Google Scholar 

  3. White, H. B. Coenzymes as fossils of an earlier metabolic state. J. Mol. Evol. 7, 101–104 (1976).

    Article  CAS  PubMed  Google Scholar 

  4. Kruger, K. et al. Self-splicing RNA: autoexcisionand autocyclization of the ribosomal RNA interveningsequence of Tetrahymena. Cell 31, 147–157 (1982).

    Article  CAS  PubMed  Google Scholar 

  5. Guerrier-Takada, C. et al. The RNA moiety of ribonuclease P is thecatalytic subunit of the enzyme. Cell 35, 849–857 (1983).

    Article  CAS  PubMed  Google Scholar 

  6. Nissan, P., Hansen, J., Ban, N., Moore, P. B. & Steitz, T. A. The structural basis of ribosome activity in peptide bond synthesis. Science 289, 920–930 (2000).

    Article  Google Scholar 

  7. Mills, D. R., Peterson, R. L. & Spiegelman, S. An extracellular darwinian evolution experiment with a self-duplicating nucleic acid molecule. Proc. Natl Acad. Sci. USA 58, 217–224 (1967).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Joyce, G. F. Forty years of in vitro evolution. Angew. Chem. Int. Ed. 46, 6420–6436 (2007). This review covers most of the test-tube evolutionary studies since the classic experiments by Spiegleman.

    Article  CAS  Google Scholar 

  9. Biebricher, C. K. & Orgel, L. E. An RNA that multiplies indefinitely with DNA-dependent RNA polymerase: selection from a random copolymer. Proc. Natl Acad. Sci. USA 70, 934–938 (1973).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Biebricher, C. K., Eigen, M, & Gardiner, W. C. Kinetics of RNA replication: competition and selection among self-replicating RNA species. Biochemistry 24, 6550–6560 (1985).

    Article  CAS  PubMed  Google Scholar 

  11. Robertson, D. L. & Joyce, G. F. Selection in vitro of an RNA enzyme that specifically cleaves singlestranded DNA. Nature 344, 467–468 (1990).

    Article  CAS  PubMed  Google Scholar 

  12. Beaudry, A. A. & Joyce, G. F. Directed evolution of an RNA enzyme. Science 257, 635–641 (1992).

    Article  CAS  PubMed  Google Scholar 

  13. Tuerk, C. & Gold, L. Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA polymerase. Science 249, 505–510 (1990).

    Article  CAS  PubMed  Google Scholar 

  14. Ellington, A. D. & Szostak, J. W. In vitro selection of RNA molecules that bind specific ligands. Nature 346, 818–822 (1990).

    Article  CAS  PubMed  Google Scholar 

  15. Chen, X., Li, N. & Ellington, A. D. Ribozyme catalysis of metabolism in the RNA world. Chem. Biodivers. 4, 633–655 (2007).

    Article  CAS  PubMed  Google Scholar 

  16. Mandal, R. & Breaker, R. R. Gene regulation byriboswitches. Nature Rev. Mol. Cell. Biol. 5, 451–463 (2004).

    Article  CAS  Google Scholar 

  17. Lincoln, T. A. & Joyce, G. F. Self-sustained replication of an RNA enzyme. Science 323, 1229–1232 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Johnston, W. K., Unrau, P. J., Lawrence, M. S., Glasner, M. E. & Bartel, D. P. RNA-catalyzed RNA polymerization: accurate and general RNA-templated primer extension. Science 292, 1319–1325 (2001). This study is the first laboratory demonstration of RNA-catalysed RNA polymerization on a template (that is, the first hint that an RNA replicase might be possible).

    Article  CAS  PubMed  Google Scholar 

  19. Zaher, H. S. & Unrau, P. J. Selection of an improved RNA polymerase ribozyme with superior extension and fidelity. RNA 13, 1017–1026 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Cheng, L. K. L. & Unrau, P. J. Closing the circle: replicating RNA with RNA. Cold Spring Harb. Perspect. Biol. 2, a002204 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Shapiro, R. Origins: A Skeptic's Guide to the Creation of Life on Earth (Bantam New Age, 1987).

    Google Scholar 

  22. Shapiro, R. A simpler origin of life. Sci. Am. 296, 46–53 (2007).

    Article  PubMed  Google Scholar 

  23. Neveu, M., Kim, H. J. & Benner, S. A. The “strong” RNA world hypothesis: fifty years old. Astrobiology 13, 391–403 (2013).

    Article  PubMed  Google Scholar 

  24. Joyce, G. F., Schwartz, A. W., Miller, S. L. & Orgel, L. E. The case for an ancestral genetic system involving simple analogues of the nucleotides. Proc. Natl Acad. Sci. USA 84, 4398–4402 (1987).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Joyce, G. F. The rise and fall of the RNA world. New Biol. 3, 399–407 (1991). This often overlooked paper lists many of the pros and cons of the RNA World hypothesis before experimental data emerged in the 1990s.

    CAS  PubMed  Google Scholar 

  26. Joyce, G. F. The antiquity of RNA-based evolution. Nature 418, 214–221 (2002).

    Article  CAS  PubMed  Google Scholar 

  27. Benner, S. A., Kim, H.J. & Carrigan, M. A. Asphalt, water, and the prebiotic synthesis of ribose, ribonucleotides, and RNA. Acc. Chem. Res. 45, 2025–2034 (2012). This paper outlines the discontinuous synthesis model of RNA synthesis, underscoring the fact that RNA need not, and probably was not, made all at once in a single environment.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  29. Vázquez-Mayagoitia, A. et al. On the stabilization of ribose by silicate minerals. Astrobiology 11, 115–121 (2011).

    Article  CAS  PubMed  Google Scholar 

  30. Anastasi, C. et al. RNA: prebiotic product, or biotic invention? Chem. Biodivers. 4, 721–739 (2007).

    Article  CAS  PubMed  Google Scholar 

  31. Powner, M. W., Gerland, B. & Sutherland, J. D. Synthesis of activated pyrimidine ribonucleotides in prebiotically plausible conditions. Nature 459, 239–242 (2009). This soon-to-be-classic paper shows how activated nucleotides can be made under abiotic conditions using the 'three-fer' of phosphate buffer.

    Article  CAS  PubMed  Google Scholar 

  32. Pasek, M. A., Harnmeijer, J. P., Buick, R., Gull, M. & Atlas, Z. Evidence for reactive reduced phosphorus species in the early Archaen ocean. Proc. Natl Acad. Sci. USA 110, 10089–10094 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Ritson, D. & Sutherland, J. D. Prebiotic synthesis of simple sugars by photoredox systems chemistry. Nature Chem. 4, 895–899 (2012).

    Article  CAS  Google Scholar 

  34. Bowler, F. R. et al. Prebiotically plausible oligoribonucleotide ligation facilitated by chemoselective acetylation. Nature Chem. 5, 383–389 (2013).

    Article  CAS  Google Scholar 

  35. Wächtershäuser, G. Before enzymes and templates: theory of surface metabolism. Microbiol. Rev. 52, 452–484 (1988).

    PubMed  PubMed Central  Google Scholar 

  36. Orgel, L. E. Did template-directed nucleation precede molecular replication? Orig. Life Evol. Biosph. 17, 27–34 (1986).

    Article  CAS  PubMed  Google Scholar 

  37. Ferris, J. P. Mineral catalysis and prebiotic synthesis: montmorillonite-catalyzed formation of RNA. Elements 1, 145–149 (2005).

    Article  CAS  Google Scholar 

  38. Monnard, P.-A., Kanavarioti, A. & Deamer, D. W. Eutectic phase polymerization of activated ribonucleotide mixtures yields quasi-equimolar incorporation of purine and pyrimidine nucleobases. J. Am. Chem. Soc. 125, 13734–13740 (2003).

    Article  CAS  PubMed  Google Scholar 

  39. Monnard, P.-A. & Szostak, J. W. Metal-ion catalyzed polymerization in the eutectic phase in water–ice: a possible approach to template-directed RNA polymerization. J. Inorg. Biochem. 102, 1104–1111 (2008).

    Article  CAS  PubMed  Google Scholar 

  40. Cafferty, B. J. et al. Efficient self-assembly in water of long noncovalent polymers by nucleobases analogs. J. Am. Chem. Soc. 135, 2447–2450 (2013). This paper reveals how there are far more RNA self-assembly mechanisms in an aqueous environment than previously appreciated.

    Article  CAS  PubMed  Google Scholar 

  41. Kuruvilla, E., Schuster, G. B. & Hud, N. V. Enhanced nonenzymatic ligation of homopurine miniduplexes: support for greater base stacking in a pre-RNA world. ChemBioChem 14, 45–48 (2013).

    Article  CAS  PubMed  Google Scholar 

  42. Hud, N. V., Cafferty, B. J., Krishnamurthy, R. & Williams, L. D. The origin of RNA and “my grandfather's axe”. Chem. Biol. 20, 466–474 (2013).

    Article  CAS  PubMed  Google Scholar 

  43. Wu, T. & Orgel, L. E. Nonenzymatic template-directed synthesis on oligodeoxycytidylate sequences in hairpin oligonucleotides. J. Am. Chem. Soc. 114, 317–322 (1992).

    Article  CAS  PubMed  Google Scholar 

  44. Hill, A. R. Jr., Wu, T. & Orgel, L. E. The limits of template-directed synthesis with nucleoside-5′-phosphoro(2-methyl)imidazolides. Origins Life Evol. Biosph. 23, 285–290 (1993).

    Article  CAS  Google Scholar 

  45. Deck, C., Jauker, M. & Richert, C. Efficient enzyme-free copying of all four nucleobases templated by immobilized RNA. Nature Chem. 3, 603–608 (2011).

    Article  CAS  Google Scholar 

  46. Lehman, N. & Hayden, E. J. Template-directed RNA polymerization: the taming of the milieu. ChemBioChem 12, 2727–2728 (2011).

    Article  CAS  PubMed  Google Scholar 

  47. Moulton, V. et al. RNA folding argues against a hot-start origin of life. J. Mol. Evol. 51, 416–421 (2000).

    Article  CAS  PubMed  Google Scholar 

  48. Vlassov, A. V., Johnston, B. H., Landweber, L. F. & Kazakov, S. A. Ligation activity of fragmented ribozymes in frozen solution: implications for the RNA world. Nucleic Acids Res. 25, 2966–2974 (2004).

    Article  CAS  Google Scholar 

  49. Wochner, A., Attwater, J., Coulson, A. & Holliger, P. Ribozyme-catalyzed transcription of an active ribozyme. Science 332, 209–212 (2011).

    Article  CAS  PubMed  Google Scholar 

  50. Attwater, J., Wochner, A. & Holliger, P. In-ice evolution of RNA polymerase ribozyme activity. Nature Chem. 5, 1011–1018 (2013). This study demonstrated polymerization by an artificial RNA replicase beyond 200 nucleotides, which is the longest achieved so far.

    Article  CAS  Google Scholar 

  51. Lehman, N. Cold-hearted RNA heats up life. Nature Chem. 5, 987–989 (2011).

    Article  CAS  Google Scholar 

  52. Huang, W. & Ferris, J. P. One-step, regioselective synthesis of up to 50-mers of RNA oligomers by montmorillonite catalysis. J. Am. Chem. Soc. 128, 8914–8919 (2006).

    Article  CAS  PubMed  Google Scholar 

  53. Kauffman, S. A. The Origins of Order: Self-Organization and Selection in Evolution (Oxford Univ. Press, 1993).

    Google Scholar 

  54. Hordijk, W. & Steel, M. Detecting autocatalytic, self-containing sets in chemical reaction systems. J. Theor. Biol. 227, 451–461 (2004).

    Article  CAS  PubMed  Google Scholar 

  55. Hordijk, W. & Steel, M. A formal model of autocatalytic sets emerging in a RNA replicator system. J. Syst. Chem. 4, 3 (2013).

    Article  CAS  Google Scholar 

  56. Smith, J. I., Steel, M. & Hordijk, W. Autocatalytic sets in a partitioned chemical network. J. Syst. Chem. 5, 2 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  57. Hayden, E. J. & Lehman, N. Self-assembly of a group I intron from inactive oligonucleotide fragments. Chem. Biol. 13, 909–918 (2006).

    Article  CAS  PubMed  Google Scholar 

  58. Hayden, E. J., von Kiedrowski, G. & Lehman, N. Systems chemistry on ribozyme self-construction: Evidence for anabolic autocatalysis in a recombination network. Angew. Chem. Int. Ed. 47, 8424–8428 (2008).

    Article  CAS  Google Scholar 

  59. Burton, A. S. & Lehman, N. Enhancing the prebiotic relevance of a set of covalently self-assembling, autorecombining RNAs through in vitro selection. J. Mol. Evol. 70, 233–241 (2010).

    Article  CAS  PubMed  Google Scholar 

  60. Vaidya, N. et al. Spontaneous network formation among cooperative RNA replicators. Nature 491, 72–77 (2012).

    Article  CAS  PubMed  Google Scholar 

  61. Vaidya, N., Walker, S. I. & Lehman, N. Recycling of informational units leads to selection of replicators in a prebiotic soup. Chem. Biol. 20, 241–252 (2013).

    Article  CAS  PubMed  Google Scholar 

  62. Levy, M. & Ellington, A. D. The descent of polymerization. Nature Struct. Biol. 8, 580–582 (2001).

    Article  CAS  PubMed  Google Scholar 

  63. Maynard Smith, J. & Szathmary, E. The Major Transitions in Evolution (Oxford University Press,1995).

    Google Scholar 

  64. Hammerstein, P. Genetic and Cultural Evolution of Cooperation (MIT Press, 2003).

    Book  Google Scholar 

  65. Nowak, M. A. Five rules for the evolution of cooperation. Science 314, 1560–1563 (2006). This paper outlines the various modes of cooperation that could be operative in biological scenarios, setting the stage for considering chemical cooperation mechanisms.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Boerlijst, M. C. & Hogeweg, P. Spiral wave structure in prebiotic evolution: hypercycles stable against parasites. Physica. D 48, 17–28 (1991).

    Article  Google Scholar 

  67. Sardanyes, J. & Solé, R. V. Bifurcations and phase transitions in spatially extended two-member hypercycles. J. Theor. Biol. 243, 468–482 (2006).

    Article  CAS  PubMed  Google Scholar 

  68. Sardanyes, J. & Solé, R. V. Spatiotemporal dynamics in simple asymmetric hypercycles under weak parasitic coupling. Physica. D 231, 116–129 (2007).

    Article  Google Scholar 

  69. McCaskill, J. S., Füchslin, R. M. & Altmeyer, S. The stochastic evolution of catalysts in spatially resolved molecular systems. Biol. Chem. 382, 1343–1363 (2001).

    Article  CAS  PubMed  Google Scholar 

  70. Konnyu, B., Czaran, T. & Szathmáry, E. Prebiotic replicase evolution in a surface-bound metabolic system: parasites as a source of adaptive evolution. BMC Evol. Biol. 8, 267 (2008).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  71. Branciamore, S., Gallori, E., Szathmáry, E. & Czaran, T. The origin of life: chemical evolution of a metabolic system in a mineral honeycomb? J. Mol. Evol. 69, 485–469 (2009).

    Article  CAS  Google Scholar 

  72. Brogioli, D. Marginally stable chemical systems as precursors for life. Phys. Rev. Lett. 105, 058102 (2010).

    Article  CAS  PubMed  Google Scholar 

  73. Szabo, P., Scheuring, I., Czaran, T. & Szathmáry, E. In silico simulations reveal that replicators with limited dispersal evolve towards higher efficiency and fidelity. Nature 420, 340–343 (2002).

    Article  CAS  PubMed  Google Scholar 

  74. Eigen, M. & Schuster, P. The hypercycle: a principle of natural self-organization. Part B: the abstract hypercycle. Naturwissenschaften 65, 7–41 (1978).

    Article  Google Scholar 

  75. Eigen, M., McCaskill, J. & Schuster, P. Molecular quasi-species. J. Phys. Chem. 92, 6881–6891 (1988).

    Article  CAS  Google Scholar 

  76. Takeuchi, N. & Hogeweg, P. Evolutionary dynamics of RNA-like replicator systems: a bioinformatic approach to the origin of life. Phys. Life Rev. 9, 219–263 (2012). This paper brings together a wide range of theories and models of RNA evolution and clearly explains the issues from evolutionary theory.

    Article  PubMed  PubMed Central  Google Scholar 

  77. Takeuchi, N. & Hogeweg, P. The role of complex formation and deleterious mutations for the stability of RNA-like replicator systems. J. Mol. Evol. 65, 668–686 (2007).

    Article  CAS  PubMed  Google Scholar 

  78. Wu, M. & Higgs, P. G. The origin of life is a spatially localized stochastic transition. Biol. Direct 7, 42 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Higgs, P. G. & Wu, M. The importance of stochastic transitions for the origin of life. Orig. Life Evol. Biosph. 42, 453–457 (2012).

    Article  CAS  PubMed  Google Scholar 

  80. Takeuchi, N. & Hogeweg, P. Evolution of complexity in RNA-like replicator systems. Biol. Direct 3, 11 (2008).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  81. Takeuchi, N. Salazar, L., Poole, A. M. & Hogeweg, P. The evolution of strand preference in simulated RNA replicators with strand displacement: implications for the origin of transcription. Biol. Direct. 3, 33 (2008).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  82. Shay, J. A., Huynh, C. & Higgs, P. G. The origin and spread of a cooperative replicase in a prebiotic chemical system. J. Theor. Biol. http://dx.doi.org/10.1016/j.jtbi.2014.09.019 (2014).

  83. Szathmáry, E. & Demeter, L. Group selection of early replicators and the origin of life. J. Theor. Biol. 128, 463–483 (1987). This early classic paper sparked considerations of how spatial aggregation might have been important in the RNA World, and it led to the concepts of molecular cooperation outlined here.

    Article  PubMed  Google Scholar 

  84. Szathmáry, E., Sandos, M. & Fernando, C. Evolutionary potential and requirements for minimal protocells. Top. Curr. Chem. 259, 167–211 (2005).

    Article  CAS  Google Scholar 

  85. Takeuchi, N. & Hogeweg, P. Multilevel selection in models of prebiotic evolution II: a direct comparison of compartmentalization and spatial self-organization. PLoS Comput. Biol. 5, e1000542 (2009).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  86. Konnyu, B. & Czaran, T. The evolution of enzyme specificity in the metabolic replicator model of prebiotic evolution. PLoS ONE 6, e20931 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Doudna, J. A., Couture, S. & Szostak, J. W. A multi-subunit ribozyme that is a catalyst of and template for complemtary strand RNA synthesis. Science 251, 1605–1608 (1991).

    Article  CAS  PubMed  Google Scholar 

  88. Ferris, J. P. Montmorillonite catalysis of 30–50 mer oligonucleotides: laboratory demonstration of potential steps in the origin of the RNA world. Orig. Life Evol. Biosph. 32, 311–332 (2002).

    Article  CAS  PubMed  Google Scholar 

  89. Lawless, J. G. & Yuen, G. U. Quantification of monocarboxylic acids in the Murchison carbonaceous meteorite. Nature 282, 396–398 (1979).

    Article  CAS  Google Scholar 

  90. Deamer, D. W. The first living systems: a bioenergetics perspective. Microbiol. Mol. Biol. Rev. 61, 239–261 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  91. Szostak, J. W., Bartel, D. P. & Luisi, P. L. Synthesizing life. Nature 409, 387–390 (2001).

    Article  CAS  PubMed  Google Scholar 

  92. Solé, R. V., Munteanu, A., Rodriguez-Caso, C. & Macía, J. Synthetic protocell biology: from reproduction to computation. Phil. Trans. Roy. Soc. B. 362, 1727–1739 (2007).

    Article  CAS  Google Scholar 

  93. Chen, I. A, Roberts R. W, & Szostak J. W. The emergence of competition between model protocells. Science 305, 1474–1476 (2004). This paper nicely shows how chemical conflicts can be solved, or exacerbated, in cell-like structures.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Adamala, K. & Szostak, J. W. Competition between model protocells driven by an encapsulated catalyst. Nature Chem. 5, 495–501 (2013).

    Article  CAS  Google Scholar 

  95. Strulson, C. A., Molden, R. C., Keating, C. D. & Bevilacqua, P. C. RNA catalysis through compartmentalization. Nature Chem. 4, 941–946 (2012).

    Article  CAS  Google Scholar 

  96. Adamala, K. & Szostak, J. W. Nonenzymatic template-directed RNA synthesis inside model protocells. Science 342, 1098–1100 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Bansho, Y. et al. Importance of parasite RNA species repression for prolonged translation-coupled RNA self-replication. Chem. Biol. 19, 478–487 (2012).

    Article  CAS  PubMed  Google Scholar 

  98. Lehman, N. Evolution finds shelter in small spaces. Chem. Biol. 19, 439–440 (2012).

    Article  CAS  PubMed  Google Scholar 

  99. Ichihashi, N. et al. Darwinian evolution in a translation-coupled RNA replication system within a cell-like compartment. Nature Commun. 4, 2494 (2013).

    Article  CAS  Google Scholar 

  100. von Kiedrowski, G., Otto, S. & Herdewijn, P. Welcome home, systems chemists! J. Syst. Chem. 1, 1 (2010).

    Article  Google Scholar 

  101. Eschenmoser, A. Chemical etiology of nucleic acid structure. Science 284, 2118–2124 (1999).

    Article  CAS  PubMed  Google Scholar 

  102. Malyshev, D. A. et al. Solution structure, mechanism of replication, and optimization of an unnatural base pair. Chem. Eur. J. 16, 12650–12659 (2010).

    Article  CAS  PubMed  Google Scholar 

  103. Yang, Z., Chen, F., Alvarado, J. B. & Benner, S. A. Amplification, mutation, and sequencing of a six-letter synthetic genetic system. J. Am. Chem. Soc. 133, 15105–15112 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Kim, E.-K. & Switzer, C. Polymerase recognition of a Watson–Crick-like metal-mediated base pair: purine-2,6-dicarboxylate·copper(II)·pyridine. ChemBioChem 14, 2403–2407 (2013).

    Article  CAS  PubMed  Google Scholar 

  105. Ebert, M. O., Mang, C., Krishnamurthy, R., Eschenmoser, A. & Jaun, B. The structure of a TNA–TNA complex in solution: NMR study of the octamer duplex derived from α-(l-threofuranosyl-)3′-2′-CGAATTCG. J. Am. Chem. Soc. 130, 15105–15115 (2008).

    Article  PubMed  Google Scholar 

  106. Yang, Y.-W., Zhang, S., McCullum, E. O. & Chaput, J. C. Experimental evidence that GNA and TNA were not sequential polymers in the prebiotic evolution of RNA. J. Mol. Evol. 65, 289–295 (2007).

    Article  CAS  PubMed  Google Scholar 

  107. Yu, H., Zhang, S. & Chaput, J. C. Darwinian evolution of an alternative genetic system provides support for TNA as an RNA progenitor. Nature Chem. 10, 183–187 (2012).

    Article  CAS  Google Scholar 

  108. Pinheiro, V. B. et al. Synthetic genetic polymers capable of heredy and evolution. Science 336, 341–344 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Schlosser, K. & Li, Y. Biologically inspired synthetic enzymes made from. DNA. Chem. Biol. 16, 315–322 (2009).

    Google Scholar 

  110. Silverman, S. K. DNA as a versatile chemical component for catalysis, encoding, and stereocontrol. Angew. Chem. Int. Ed. 49, 7180–7201 (2010).

    Article  CAS  Google Scholar 

  111. Lazcano, A., Guerrero, R., Margulis, L. & Oro, J. The evolutionary transition from RNA to DNA in early cells. J. Mol. Evol. 27, 283–290 (1988).

    Article  CAS  PubMed  Google Scholar 

  112. Burton, A. S. & Lehman, N. DNA before proteins? Recent discoveries in nucleic acid catalysis strengthen the case. Astrobiology. 9, 125–130 (2009).

    Article  CAS  PubMed  Google Scholar 

  113. Ohtsuki, H. & Nowak, M. A. Prelife catalysts and replicators. Proc. Roy. Soc. B 276, 3783–3790 (2009).

    Article  Google Scholar 

  114. Manapat, M. L., Chen, I. A. & Nowak, M. A. The basic reproductive ratio of life. J. Theor. Biol. 263, 317–327 (2010).

    Article  PubMed  Google Scholar 

  115. Chen, I. A. & Nowak. M. A. From prelife to life: how chemical kinetics become evolutionary dynamics. Acc. Chem. Res. 45, 2088–2096 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Wu, M. & Higgs, P. G. Origin of self-replicating biopolymers: autocatalytic feedback can jump-start the RNA world. J. Mol. Evol. 69, 541–554 (2009).

    Article  CAS  PubMed  Google Scholar 

  117. Wu, M. & Higgs, P. Comparison of the roles of momoner synthesis, polymerization, and recombination in the origin of autocatalytic sets of biopolymers. Astrobiology 11, 895–906 (2011).

    Article  CAS  PubMed  Google Scholar 

  118. Ma, W., Yu, C., Zhang, W. & Hu, J. A simple template-dependent ligase ribozyme as the RNA replicase emerging first in the RNA World. Astrobiology 10, 437–447 (2010).

    Article  CAS  PubMed  Google Scholar 

  119. Ma, W., Yu, C., Zhang, W. & Hu, J. Nucleotide synthetase ribozymes may have emerged first in the RNA World. RNA 13, 2012–2019 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Ma, W., Yu, C. & Zhang, W. Monte Carlo simulation of early molecular evolution in the RNA World. Biosystems 90, 28–39 (2007).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors thank H. Lonsdale's Origin-of-Life Challenge for supporting the ideas and research mentioned in this work.

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Glossary

RNA riboswitches

RNA molecules that respond to environmental conditions by changing secondary structure — and, in some cases, by modulating catalytic function — thereby affecting gene expression.

Ligases

Enzymes that covalently join polymers using ATP-derived energy.

Cooperation

The phenomenon whereby two or more entities interact to provide benefits for themselves that are greater than those possible by the operations of the entities in isolation.

Protocells

Membrane-enclosed compartments that may not contain all the components of present-day cells but that were presumably capable of some rudimentary means of growth and division. They can also refer to artificial cell-like structures created in the laboratory.

Activated

In this context, pertaining to nucleotides that are primed with a high-energy bond to facilitate their condensation with other nucleotides.

Eutectic phase

A chemical mixture that has a lower freezing point than a composition of pure ingredients.

Class I ligase ribozyme

A ribozyme selected from a random pool of RNAs that can catalyse the ligation of an exogenous fragment of RNA to its own 5′ end.

Autocatalytic set

A collection of molecules that mutually cooperate in the sense that none of them can replicate without all the others, such that the reactions that form the components of the set are catalysed by other components of the set.

Altruism

When one individual provides a benefit to another while gaining no benefit itself (or even while suffering a detriment).

Hypercycles

Cooperative replicative sets of molecules in which hyperbolic growth is possible.

Error threshold

The theoretical maximum mutation rate that can sustain information genetic polymers of a particular length.

Group selection

Selection that acts on a group of entities as a whole (such as animals living in a social group or molecules inside a protocell) and that favours survival of the whole group, in contrast to selection acting on individual members of a group that leads to competition between the individuals.

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Higgs, P., Lehman, N. The RNA World: molecular cooperation at the origins of life. Nat Rev Genet 16, 7–17 (2015). https://doi.org/10.1038/nrg3841

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