Journal of Molecular Evolution

, Volume 41, Issue 6, pp 693–702 | Cite as

Are polyphosphates or phosphate esters prebiotic reagents?

  • Anthony D. Keefe
  • Stanley L. Miller


It is widely held that there was a phosphate compound in prebiotic chemistry that played the role of adenosine triphosphate and that the first living organisms had ribose-phosphate in the backbone of their genetic material. However, there are no known efficient prebiotic synthesis of high-energy phosphates or phosphate esters. We review the occurrence of phosphates in Nature, the efficiency of the volcanic synthesis of P4O10, the efficiency of polyphosphate synthesis by heating phosphate minerals under geological conditions, and the use of high-energy organic compounds such as cyanamide or hydrogen cyanide. These are shown to be inefficient processes especially when the hydrolysis of the polyphosphates is taken into account. For example, if a whole atmosphere of methane or carbon monoxide were converted to cyanide which somehow synthesized polyphosphates quantitatively, the polyphosphate concentration in the ocean would still have been insignificant. We also attempted to find more efficient high-energy polymerizing agents by spark discharge syntheses, but without success. There may still be undiscovered robust prebiotic syntheses of polyphosphates, or mechanisms for concentrating them, but we conclude that phosphate esters may not have been constituents of the first genetic material. Phosphoanhydrides are also unlikely as prebiotic energy sources.

Key words

Orthophosphate Polyphosphates Phosphorus pentoxide Phosphate minerals High-energy organic compounds Thermal condensation 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Arrhenius G, Gedulin B, Mcjzsis S (1993) Phosphate in models for chemical evolution. In: Ponnamperuma C, Chela-Flores J (eds) Conference on chemical evolution and the origin of life, proceedings, Trieste, 1992. A. Deepak Publishing, Hampton, VA, pp 25–50Google Scholar
  2. Baltscheffsky H (1993) Chemical origin and early evolution of biological energy conversion. In: Ponnamperuma C, Chela-Flores J (eds) Conference on chemical evolution and the origin of life, proceedings, Trieste, 1992. A. Deepak Publishing, Hampton, VA, pp 13–23Google Scholar
  3. Beck A, Orgel LE (1965) The formation of condensed phosphate in aqueous solution. Proc Natl Acad Sci USA 54:664–667Google Scholar
  4. Berzelius, JJ (1816) Untersuchungen über die Zusammensetzung der Phosphorsäure, der phosphorigen Säure und ihrer Salze. Ann Physik 53:393–446Google Scholar
  5. Bishop, MJ, Lohrmann, R, Orgel, LE (1972) Prebiotic phosphorylation of thymidine at 65°C in simulated desert conditions. Nature 237: 162–164Google Scholar
  6. Byrappa, K (1983) The possible reasons for the absence of condensed phosphates in Nature. Phys Chem Miner 10:94–95Google Scholar
  7. Cairns-Smith, AG (1982) Genetic takeover and the mineral origins of life. Cambridge University Press, Cambridge, EnglandGoogle Scholar
  8. de Duve, C (1991) Blueprint for a cell: the nature and origin of life. N. Patterson Publishers, Burlington, NCGoogle Scholar
  9. Egholm, M, Buchardt, O, Nielsen, PE, Berg, RH (1992) Peptide nucleic acids (PNA). Oligonucleotide analogues with an achiral peptide backbone. J Am Chem Soc 114:1895–1897Google Scholar
  10. Ferris JP (1968) Cyanovinyl phosphate: a prebiological phosphorylating agent? Science 161:53–54Google Scholar
  11. Ferris JP, Goldstein G, Beaulieu DJ (1970) Chemical evolution IV. An evaluation of Cyanovinyl phosphate as a prebiotic phosphorylating agent. J Am Chem Soc 92:6598–6603Google Scholar
  12. Ferris, JP, Yanagawa, H, Dudgeon, PA, Hagan Jr WJ, Mallare, TE (1984) The investigation of the HCN derivative diiminosuccinonitrile as a prebiotic condensing agent. The formation of phosphate esters. Orig Life 15:29–43Google Scholar
  13. Gabel, NW (1968) Abiotic formation of phosphoric anhydride bonds in dilute aqueous conditions. Nature 218:354Google Scholar
  14. Halmann, M, Sanchez, RA, Orgel LE (1969) Phosphorylation of D-ribose in aqueous solution. J Org Chem 34:3702–3703Google Scholar
  15. Halmann, M, Schmidt, H-L (1970) Cyanogen-induced synthesis of 18O-labelled β-ribofuranose-1-phosphate and its acid-catalysed hydrolysis. J Chem Soc (C) 1970:1191–1193Google Scholar
  16. Hanafusa, H, Akabori, S (1959) Polymerization of aminoacetonitrile. Bull Chem Soc Jpn 32:626–630Google Scholar
  17. Handschuh, GJ, Orgel, LE (1973) Struvite and prebiotic phosphorylation. Science 179:483–484Google Scholar
  18. Handschuh, GJ, Lohrmann, R, Orgel, LE (1973) The effect of Mg2+ and Ca2+ on urea-catalyzed phosphorylation reactions. J Mol Evol 2:251–262Google Scholar
  19. Hulshof, J, Ponnamperuma, C (1976) Prebiotic condensation reactions in an aqueous medium: a review of condensing agents. Orig Life 7:197–224Google Scholar
  20. Kanaya, E, Yanagawa, H (1986) Template-directed polymerization of oligoadenylates using cyanogen bromide. Biochemistry 25:7423–7430Google Scholar
  21. Keefe AD, Miller SL (1996) Potentially prebiotic syntheses of condensed phosphates. Orig Life Evol. Biosphere (in press)Google Scholar
  22. Kornberg, A (1995) Inorganic polyphosphate: toward making a forgotten polymer unforgettable. J Bacteriol 177:491–496Google Scholar
  23. Krane, SM, Glimcher, MJ (1962) Transphosphorylation from nucleoside di- and triphosphates by apatite crystals. J Biol Chem 237: 2991–2998Google Scholar
  24. Li, T, Nicolaou, KC (1994) Chemical self-replication of palindromic duplex DNA. Nature 369:218–221Google Scholar
  25. Lohrmann, R, Orgel, LE (1968) Prebiotic synthesis: phosphorylation in aqueous solution. Science 161:64–66Google Scholar
  26. Lohrmann, R, Orgel, LE (1971) Urea-inorganic phosphate mixtures as prebiotic phosphorylating agents. Science 171:490–494Google Scholar
  27. Lohrmann, R, Orgel, LE (1973) Prebiotic activation processes. Nature 244:418–420Google Scholar
  28. Losse, G, Anders, K (1961) Die Polymerisation von α-Aminopropionitril an mineralischen Trägern als Modell für die primäre Bildung von Eiweißstoffen auf der Erde. Z. Physiol Chem 323: 111–115Google Scholar
  29. Martens, CS, Harriss, RC (1970) Inhibition of apatite precipitation in the marine environment by magnesium ions. Geochim Cosmochim. Acta 34:621–625Google Scholar
  30. Mazghouni, M, Kbir-Ariguib, N, Counioux, JJ, Sebaoun, A (1981) Etude des equilibres solide-liquide-vapeur des systemes binaires K3PO4-H2O et Mg3(PO4)2-H2O. Thermochim Acta 47:125–139Google Scholar
  31. Miller, SL, Parris, M (1964) Synthesis of pyrophosphate under primitive Earth conditions. Nature 204:1248–1250Google Scholar
  32. Miller SL, Orgel LE (1974) The origins of life on the earth. Prentice Hall, Englewood Cliffs, NJGoogle Scholar
  33. Moser, RE, Matthews, CN (1968) Hydrolysis of aminoacetonitrile: peptide formation. Experientia 24:658–659PubMedGoogle Scholar
  34. Nelsestuen, GL (1980) Origin of life: consideration of alternatives to proteins and nucleic acids. J Mol Evol 15:59–72Google Scholar
  35. Nriagu, JO, Moore, PB (1984) Phosphate minerals. Springer-Verlag, BerlinGoogle Scholar
  36. Österberg, R, Orgel, LE (1972) Polyphosphate and trimetaphosphate formation under potentially prebiotic conditions. J Mol Evol 1:241–248Google Scholar
  37. Österberg, R, Orgel, LE, Lohrmann, R (1973) Further studies of urea-catalyzed phosphorylation reactions. J Mol Evol 2:231–234Google Scholar
  38. Palache, C, Berman, H, Frondel, C (1951) Dana's system of mineralogy, 7th ed, vol 2. John Wiley and Sons, New YorkGoogle Scholar
  39. Pitsch, S, Pombo-Villar, E, Eschenmoser, A (1994) Chemistry of α-aminonitriles. Formation of 2-oxoethyl phosphates (“glycoaldehyde phosphates”) from rac-oxiranecarbonitrile and on (formal) constitutional relationships between 2-oxoethyl phosphates and oligo (hexo- and pentopyranosyl) nucleotide backbones. Helv Chim Acta 77:2251–2285Google Scholar
  40. Ponnamperuma, C, Mack, R (1965) Nucleotide synthesis under possible primitive Earth conditions. Science 148:1221–1223Google Scholar
  41. Prager, B, Jacobson, P. (eds) (1918–1940) Beilsteins Handbuch der organischen Chemie. Springer-Verlag, BerlinGoogle Scholar
  42. Rabinowitz, J, Chang, S, Ponnamperuma, C (1968) Phosphorylation on the primitive earth. Nature 218:442–443Google Scholar
  43. Rouse RC, Peacor DR, Freed RL (1988) Pyrophosphate groups in the structure of canaphite, CaNa2P2O7 · 4H2O: the first occurrence of a condensed phosphate as a mineral. Am Miner 73:168–171Google Scholar
  44. Sales, BC, Chakoumakos, BC, Boatner, LA, Ramey JO (1992) Structural evolution of the amorphous solids produced by heating crystalline MgHPO4 · 3H2O. J Mater Res 7(10):2646–2649Google Scholar
  45. Sales, BC, Chakoumakos, BC, Boatner, LA, Ramey JO(1993) Structural properties of the amorphous phases produced by heating crystalline MgHPO4 · 3H20. J Non-cryrystall Solids 159:121–139Google Scholar
  46. Saygin, Ö (1981) Nonenzymatic photophosphorylation with visible light. A possible mode of prebiotic ATP formation. Naturwissenschaften 68:617–619Google Scholar
  47. Saygin, Ö (1983) Nonenzymatic phosphorylation of acetate by carbamyl phosphate. A model reaction for prebiotic activation of carboxyl groups. Orig Life 13:43–48Google Scholar
  48. Schwartz, AW, Van der Veen, M, Bisseling, T, Chittenden, GJF (1975) Prebiotic nucleotide synthesis—demonstration of a geologically plausible pathway. Orig Life 6:163–168Google Scholar
  49. Sievers, D, von Kiedrowski, G (1994) Self-replication of complementary nucleotide-based oligomers. Nature 369:221–224Google Scholar
  50. Shapiro, R (1986) Origins, a skeptic's guide to the creation of life on earth. Simon and Schuster, New YorkGoogle Scholar
  51. Sherwood, E, Oró, J (1977) Cyanamide mediated syntheses under plausible primitive earth conditions I. The synthesis of P1, P2 dideoxythymidine 5′-pyrophosphate. J Mol Evol 10:183–192PubMedGoogle Scholar
  52. Sherwood E, Joshi A, Oró J (1977) Cyanamide mediated syntheses under plausible primitive earth conditions II. The polymerization of deoxythymidine 5′-triphosphate. J Mol Evol 10:193–209Google Scholar
  53. Steinman, G, Lemmon, RM, Calvin, M (1964) Cyanamide: a possible key compound in chemical evolution. Proc Natl Acad Sci USA 52:27–30Google Scholar
  54. Steinman, G, Kenyon, DH, Calvin, M (1965) Dehydration condensation in aqueous solution. Nature 206:707–708Google Scholar
  55. Tarelli, E, Wheeler, SF (1993) Formation of esters, especially phosphate esters, under ‘dry’ conditions and ‘mild’ pH. Chem Industry 1993:164–165Google Scholar
  56. Van Wazer, JR (1958) Phosphorus and its compounds, vol 1. Interscience, New YorkGoogle Scholar
  57. Vinogradov, AP (1956) Regularity of distribution of chemical elements in the Earth's crust. Geochemistry 44:1–43Google Scholar
  58. Weber, AL (1981) Formation of pyrophosphate, tripolyphosphate, and phosphorylimidazole with the thioester, N, S-diacetylcysteamine, as the condensing agent. J Mol Evol 18:24–29Google Scholar
  59. Weber, AL (1982) Formation of pyrophosphate on hydroxyapatite with thioesters as condensing agents. Biosystems 15:183–189Google Scholar
  60. Westheimer, FH (1987) Why Nature chose phosphates. Science 235: 1173–1178Google Scholar
  61. Wood, HG (1985) Inorganic pyrophosphate and polyphosphates as sources of energy. Curr Top Cell Regul 26:355–369Google Scholar
  62. Yamagata, Y, Matsukawa, T, Mohri, T, Inomata, K (1979) Phosphorylation of adenosine in aqueous solution by electric discharges. Nature 282:284–286Google Scholar
  63. Yamagata, Y, Mohri, T, Yamakoshi, M, Inomata, K (1981) Constant AMP synthesis in aqueous solution by electric discharges. Orig Life 11:233–235Google Scholar
  64. Yamagata, Y, Mohri, T (1982) Formation of cyanate and carbamyl phosphate by electric discharges of model primitive gas. Orig Life 12:41–44Google Scholar
  65. Yamagata, Y, Watanabe, H, Saitoh, M, Namba, T (1991) Volcanic production of polyphosphates and its relevance to prebiotic evolution. Nature 352:516–519Google Scholar

Copyright information

© Springer-Verlag New York Inc 1995

Authors and Affiliations

  • Anthony D. Keefe
    • 1
  • Stanley L. Miller
    • 1
  1. 1.Department of Chemistry and BiochemistryUniversity of CaliforniaSan Diego, La JollaUSA

Personalised recommendations