Journal of Molecular Evolution

, Volume 61, Issue 2, pp 264–273 | Cite as

The RNA World on Ice: A New Scenario for the Emergence of RNA Information

  • Alexander V. Vlassov
  • Sergei A. Kazakov
  • Brian H. Johnston
  • Laura F. LandweberEmail author


The RNA world hypothesis refers to a hypothetical era prior to coded peptide synthesis, where RNA was the major structural, genetic, and catalytic agent. Though it is a widely accepted scenario, a number of vexing difficulties remain. In this review we focus on a missing link of the RNA world hypothesis—primitive miniribozymes, in particular ligases, and discuss the role of these molecules in the evolution of RNA size and complexity. We argue that prebiotic conditions associated with freezing, rather than “warm and wet” conditions, could have been of key importance in the early RNA world.


RNA world Miniribozymes RNA evolution Freezing catalysis 


  1. Bada JL, Bigham C, Miller SL (1994) Impact melting of frozen oceans on the early Earth: implications for the origin of life. Proc Natl Acad Sci USA 91:1248–1250PubMedGoogle Scholar
  2. Bada JL, Lazcano A (2002) Origin of life Some like it hot, but not the first biomolecules. Science 296:1982–1983CrossRefPubMedGoogle Scholar
  3. Bartel DP, Szostak JW (1993). Isolation of new ribozymes from a large pool of random sequences. Science 261:1411–1418PubMedGoogle Scholar
  4. Berzal-Herranz A, Joseph S, Burke JM (1992). In vitro selection of active hairpin ribozymes by sequential RNA-catalyzed cleavage and ligation reactions. Genes Dev 6:129–134PubMedGoogle Scholar
  5. Berzal-Herranz A, Joseph S, Chowrira BM, Butche SE, Burke JM (1993). Essential nucleotide sequences and secondary structure elements of the hairpin ribozyme. EMBO J 12:2567–2573PubMedGoogle Scholar
  6. Bruce TC, Butler AR (1964) Catalysis in water and ice. II. The reaction of thiolactones with morpholine in frozen systems. J Am Chem Soc 86:4104–4108CrossRefGoogle Scholar
  7. Butcher SE, Heckman JE, Burke JM (1995) Reconstitution of hairpin ribozyme activity following separation of functional domains. J Biol Chem 270:29648–29651CrossRefPubMedGoogle Scholar
  8. Chowrira BM, Berzal-Herranz A, Burke JM (1991) Novel guanosine requirement for catalysis by the hairpin ribozyme. Nature 354:320–322CrossRefPubMedGoogle Scholar
  9. Chowrira BM, Burke JM (1992) Extensive phosphorothioate substitution yields highly active and nuclease–resistant hairpin ribozymes. Nucleic Acids Res 20:2835–2840PubMedGoogle Scholar
  10. Clifford SM, Parker TJ (2001) The evolution of the martian hydrosphare: implications for the fate of a primordial ocean and the current state of the northern plains. Icarus 154:40–79CrossRefGoogle Scholar
  11. Collins RA (2002) The neurospora varkud satellite ribozyme. Biochem Soc Trans 30:1122–1126CrossRefPubMedGoogle Scholar
  12. Dange V, Van Atta RB, Hecht SM (1990) A Mn2(+)–dependent ribozyme. Science 248:585–588PubMedGoogle Scholar
  13. Ding PZ, Kawamura K, Ferris JP (1996) Oligomerization of uridine phosphorimidazolides on montmorillonite: a model for the prebiotic synthesis of RNA on minerals. Orig Life Evol Biosph 26:151–171CrossRefPubMedGoogle Scholar
  14. Fedor MJ (2002) The role of metal ions in RNA catalysis. Curr Opin Struct Biol 12:289–295CrossRefPubMedGoogle Scholar
  15. Fedorova O, Su LJ, Pyle AM (2002) Group II introns: highly specific endonucleases with modular structures and diverse functions. Methods 28:323–335CrossRefPubMedGoogle Scholar
  16. Feig (2000) The use of manganese as a probe for elucidating the role of magnesium ions in ribozymes. Met Ions Biol Syst 37:157–182Google Scholar
  17. Ferris JP, Hill JAR, Liu R, Orgel LE (1996) Synthesis of long prebiotic oligomers on mineral surfaces. Nature 381:59–61CrossRefPubMedGoogle Scholar
  18. Gilbert W (1986) The RNA World. Nature 319:618CrossRefGoogle Scholar
  19. Grant NH, Alburn HE (1965) Fast reactions of ascorbic acid and hydrogen peroxide in ice, a presumably early environment. Science 150:1589–1590 Google Scholar
  20. Grant NH, Alburn HE (1966) Acceleration of enzyme reactions in ice. Nature 212:194Google Scholar
  21. Grant NH, Clark DE, Alburn HE (1961) Imidazole and base-catalyzed hydrolysis of penicillin in frozen systems. J Am Chem Soc 83:4476–4477CrossRefGoogle Scholar
  22. Gryaznov SM, Letsinger RL (1993) Chemical ligation of oligonucleotides in the presence and absence of a template. J Am Chem Soc 115:3808–3809CrossRefGoogle Scholar
  23. Harris RJ, Elder D (2000) Ribozyme relationships: the hammerhead, hepatitis delta, and hairpin ribozymes have a common origin. J Mol Evol 51:182–184PubMedGoogle Scholar
  24. Holland HD (1984) Chemical evolution of the atmosphere and oceans. Princeton University Press, Princeton, NJGoogle Scholar
  25. Jadhav VR, Yarus M (2002) Coenzymes as coribozymes. Biochimie 84:877–888CrossRefPubMedGoogle Scholar
  26. Johnston WK, Unrau PJ, Lawrence MS, Glasner ME, Bartel DP (2001) RNA-catalyzed RNA polymerization: accurate and general RNA-templated primer extension. Science 292:1319–1325CrossRefPubMedGoogle Scholar
  27. Joseph S, Burke JM (1993) Optimization of an anti-HIV hairpin ribozyme by in vitro selection. J Biol Chem 268:24515–24518PubMedGoogle Scholar
  28. Joyce G (2002) The antiquity of RNA-based evolution. Nature 418:214–221CrossRefPubMedGoogle Scholar
  29. Joyce GF (2004) Directed evolution of nucleic acid enzymes. Annu Rev Biochem 73:791–836CrossRefPubMedGoogle Scholar
  30. Kanavarioti A, Monnard P-A, Deamer DW (2001) Eutectic phases in ice facilitate nonenzymatic nucleic acid synthesis. Astrobiology 1:271–281CrossRefPubMedGoogle Scholar
  31. Kazakov SA (1996) Nucleic acid binding and catalysis by metal ions. In: Hecht SM (ed) Bioorganic chemistry: Nucleic acids. Oxford University Press, New York, pp 244–287, 467–476Google Scholar
  32. Kazakov S, Altman S (1992). A trinucleotide can promote metal ion-dependent specific cleavage of RNA. Proc Natl Acad Sci USA 89:7939–7943PubMedGoogle Scholar
  33. Kazakov SA, Balatskaya SV, Johnston BH (1998) Freezing-induced self-ligation of the hairpin ribozyme: cationic effects. In: Sarma RH, Sarma MH (eds) Structure, motion, interaction and expression of biological macromolecules. Adenine Press, Albany, New York, pp 155–161Google Scholar
  34. Kiovsky TE, Pincock RE (1966) The mutarotation of glucose in frozen aqueous solutions. J Am Chem Soc 88:4704–4710CrossRefGoogle Scholar
  35. Kirsebom LA (2002) RNase P RNA-mediated catalysis. Biochem Soc Trans 30:1153–1158CrossRefPubMedGoogle Scholar
  36. Kumar R, Yarus M (2001) RNA-catalyzed amino acid activation. Biochemistry 40:6998–7004PubMedGoogle Scholar
  37. Kuntz ID, Brassfield TS, Law GD, Purcell GV (1969) Hydration of macromolecules. Science 163:1329–1331PubMedGoogle Scholar
  38. Lacey JC Jr, Staves MP, Thomas RD (1990) Ribonucleic acids may be catalysts for the preferential synthesis of L-amino acid peptides: a minireview. J Mol Evol 31:244–248PubMedGoogle Scholar
  39. Landweber L (1999) Experimental RNA Evolution. TREE 14:353–358PubMedGoogle Scholar
  40. Landweber LF, Pokrovskaya ID (1999) Emergence of a dual-catalytic RNA with metal-specific cleavage and ligase activities: the spandrels of RNA evolution. Proc Natl Acad Sci USA 96:173–178CrossRefPubMedGoogle Scholar
  41. Landweber LF, Simon PJ, Wagner TA (1998) Ribozyme design and early evolution. BioScience 48:94–103Google Scholar
  42. Larralde R, Robertson MP, Miller SL (1995) Rates of decomposition of ribose and other sugars: implications for chemical evolution. Proc Natl Acad Sci USA 92:8158–8160PubMedGoogle Scholar
  43. Lazcano A, Miller SL (1996) The origin and early evolution of life: prebiotic chemistry, the pre-RNA world, and time. Cell 85:793–798CrossRefPubMedGoogle Scholar
  44. Lee DH, Granja JR, Martinez JA, Severin K, Ghadiri MR (1996) A self-replicating peptide. Nature 382(6591):525–528CrossRefPubMedGoogle Scholar
  45. Leman L, Orgel L, Ghadiri MR (2004) Carbonyl sulfide-mediated prebiotic formation of peptides. Science 306(5694):283–286CrossRefPubMedGoogle Scholar
  46. Levy M, Miller SL (1998) The stability of the RNA bases: implications for the origin of life. Proc Natl Acad Sci USA 95:7933–7938CrossRefPubMedGoogle Scholar
  47. Levy M, Miller SL, Oró J (1999) Production of guanine from NH(4)CN polymerizations. J Mol Evol 49:165–168PubMedGoogle Scholar
  48. Lilley DM (2003) The origins of RNA catalysis in ribozymes. Trends Biochem Sci 28:495–501CrossRefPubMedGoogle Scholar
  49. Liu R, Orgel LE (1997) Efficient oligomerization of negatively-charged beta-amino acids at −20 degrees. CJ Am Chem Soc 119(20):4791–4792CrossRefPubMedGoogle Scholar
  50. Lundbäck T, Härd T (1996) Sequence-specific DNA-binding dominated by dehydration. Proc Natl Acad Sci USA 93:4754–4759CrossRefPubMedGoogle Scholar
  51. McGinness KE, Joyce GF (2003) In search of an RNA replicase ribozyme. Chem Biol 10:5–14CrossRefPubMedGoogle Scholar
  52. Meierhenrich UJ, Munoz Caro GM, Bredehoft JH, Jessberger EK, Thiemann WH (2004) Identification of diamino acids in the Murchison meteorite. Proc Natl Acad Sci USA 101(25):9182–9186CrossRefPubMedGoogle Scholar
  53. Miller SL (1953) A production of amino acids under possible primitive earth conditions. Science 117:528–529PubMedGoogle Scholar
  54. Miyakawa S, Cleaves HJ, Miller SL (2002) The cold origin of life: B. Implications based on pyrimidines and purines produced from frozen ammonium cyanide solutions. Orig Life Evol Biosph 32:209–218CrossRefPubMedGoogle Scholar
  55. Monnard P-A, Kanavarioti A, Deamer D (2003) Eutectic phase polymerization of activated ribonucleotide mixtures yields quasi-equimolar incorporation of purine and pyrimidine nucleobases. J Am Chem Soc 125:13734–13740CrossRefPubMedGoogle Scholar
  56. Monnard P-A (2005) Catalysis in abiotic structured media: an approach to selective synthesis of biopolymers. Cell Mol Life Sci 62:520–534CrossRefPubMedGoogle Scholar
  57. Murray JB, Seyhan AA, Walter NG, Burke JM, Scott WG (1998) The hammerhead, hairpin and VS ribozymes are catalytically proficient in monovalent cations alone. Chem Biol 5:587–595CrossRefPubMedGoogle Scholar
  58. Nesbitt SM, Erlacher HA, Fedor MJ (1999) The internal equilibrium of the hairpin ribozyme: temperature, ion and pH effects. J Mol Biol 286:1009–1024CrossRefPubMedGoogle Scholar
  59. Orgel LE, Lohrmann R (1974) Prebiotic chemistry and nucleic acid replication. Acc Chem Res 7:368–377CrossRefGoogle Scholar
  60. Pace NR (1991) Origin of life—Facing up to the physical setting. Cell 65:531–533CrossRefPubMedGoogle Scholar
  61. Prusoff WH (1963) Low-temperature reversal of the ultraviolet photochemical reaction product of 2′-deoxyuridive. Biochim Biophys Acta 68:302–310CrossRefPubMedGoogle Scholar
  62. Psenner R, Sattler B (1998) Life at the freezing point. Science 280:2073–2074CrossRefPubMedGoogle Scholar
  63. Pyle AM (1993) Ribozymes: a distinct class of metalloenzymes. Science 261:709–714PubMedGoogle Scholar
  64. Pyle AM (2002) Metal ions in the structure and function of RNA. J Biol Inorg Chem 7:679–690CrossRefPubMedGoogle Scholar
  65. Rau DC, Le B, Parsegian VA (1984) Measurement of the repulsive force between polyelectrolyte molecules in ionic solution: hydration forces between parallel DNA double helices. Proc Natl Acad Sci USA 81:2621–2625PubMedGoogle Scholar
  66. Renz M, Lohrmann R, Orgel LE (1971) Catalysts for the polymerization of adenosine cyclic 2′, 3′–phosphate on a poly(U) template. Biochim Biophys Acta 240:463–471PubMedGoogle Scholar
  67. Ricardo A, Carrigan MA, Olcott AN, Benner SA (2004) Borate minerals stabilize ribose. Science 9:196CrossRefGoogle Scholar
  68. Sanchez R, Ferris J, Orgel LE (1966) Condition for purine synthesis: Did prebiotic synthesis occur at low temperatures? Science 153:72–73PubMedGoogle Scholar
  69. Schmidt F (1999) Ribozymes—Why so many, why so few? Mol Cells 9:459–463PubMedGoogle Scholar
  70. Schuster M, Aaviksaar A, Haga M, Ullmann U, Jakubke HD (1991) Protease-catalyzed peptide synthesis in frozen aqueous systems: the “freeze-concentration model.” Biomed Biochim Acta 50:84–89Google Scholar
  71. Siwkowski A, Humphrey M, De-Young MB, Hampel A (1998) Screening for important base identities in the hairpin ribozyme by in vitro selection for cleavage. Biotechniques 24:278–284PubMedGoogle Scholar
  72. Squyres SW, Grotzinger JP, Arvidson RE, Bell JF III, Calvin W, Christensen PR, Clark BC, Crisp JA, Farrand WH, Herkenhoff KE, Johnson JR, Klingelhofer G, Knoll AH, McLennan SM, McSween HY Jr, Morris RV, Rice JW Jr, Rieder R, Soderblom LA (2004) In situ evidence for an ancient aqueous environment at Meridiani Planum, Mars. Science 306:1709–1714CrossRefPubMedGoogle Scholar
  73. Szathmary E (1999) The origin of the genetic code: amino acids as cofactors in an RNA worldTrends Genet 15:223–229CrossRefPubMedGoogle Scholar
  74. Tamura K, Alexander RW (2004) Peptide synthesis through evolution. Cell Mol Life Sci 61:1317–1330CrossRefPubMedGoogle Scholar
  75. Tõugu V, Talts P, Meos H, Haga M, Aaviksaar A (1995) Aminolysis of acyl-chymotrypsins by amino acids. Kinetic appearance of concentration effect in peptide yield enhancement by freezing. Biochim Biophys Acta 1247:272–276PubMedGoogle Scholar
  76. Usher DA (1977) Early chemical evolution of nucleic acids: a theoretical model. Science 196:311–313PubMedGoogle Scholar
  77. Van Atta RB, Hecht SM (1994) A ribozyme model: site-specific cleavage of an RNA substrate by Mn2+. Adv Inorg Biochem 9:1–40PubMedGoogle Scholar
  78. Vlassov A, Khvorova A, Yarus M (2001) Binding and disruption of phospholipid bilayers by supramolecular RNA complexes. Proc Natl Acad Sci USA 98:7706–7711CrossRefPubMedGoogle Scholar
  79. Vlassov AV, Johnston BH, Landweber LF, Kazakov SA (2004) Ligation activity of fragmented ribozymes in frozen solution: implications for the RNA world. Nucleic Acids Res 32:2966–2974CrossRefPubMedGoogle Scholar
  80. Walter NG, Burke JM (1998) The hairpin ribozyme: structure, assembly and catalysis. Curr Opin Chem Biol 2:24–30CrossRefPubMedGoogle Scholar
  81. Walter NG, Engelke DR (2002) Ribozymes: catalytic RNAs that cut things, make things, and do odd and useful jobs. Biologist 49:199–203PubMedGoogle Scholar
  82. Weber AL, Miller SL (1981) Reasons for the occurrence of the twenty coded protein amino acids. J Mol Evol 17:273–284CrossRefPubMedGoogle Scholar
  83. Westhof E (2002) Group I introns and RNA folding. Biochem Soc Trans 30:1149–1152CrossRefPubMedGoogle Scholar
  84. Yarus M (1999) Boundaries for an RNA world. Curr Opin Chem Biol 3:260–267CrossRefPubMedGoogle Scholar
  85. Yarus M, Caporase JG, Knight R (2005) ORIGINS OF THE GENETIC CODE: The Escaped Triplet Theory. Annu Rev Biochem 74:179–198CrossRefPubMedGoogle Scholar
  86. Zhang B, Cech TR (1997) Peptide bond formation by in vitro selected ribozymes. Nature 390:96–100Google Scholar

Copyright information

© Springer Science+Business Media, Inc. 2005

Authors and Affiliations

  • Alexander V. Vlassov
    • 1
  • Sergei A. Kazakov
    • 1
  • Brian H. Johnston
    • 1
    • 3
  • Laura F. Landweber
    • 2
    Email author
  1. 1.SomaGenics, Inc.Santa CruzUSA
  2. 2.Department of Ecology and Evolutionary BiologyPrinceton, UniversityPrincetonUSA
  3. 3.Department of PediatricsStanford University School of MedicineStanfordUSA

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