Chemical Evolution and the Evolutionary Definition of Life


Darwinian evolution requires a mechanism for generation of diversity in a population, and selective differences between individuals that influence reproduction. In biology, diversity is generated by mutations and selective differences arise because of the encoded functions of the sequences (e.g., ribozymes or proteins). Here, I draw attention to a process that I will call chemical evolution, in which the diversity is generated by random chemical synthesis instead of (or in addition to) mutation, and selection acts on physicochemical properties, such as hydrolysis, photolysis, solubility, or surface binding. Chemical evolution applies to short oligonucleotides that can be generated by random polymerization, as well as by template-directed replication, and which may be too short to encode a specific function. Chemical evolution is an important stage on the pathway to life, between the stage of “just chemistry” and the stage of full biological evolution. A mathematical model is presented here that illustrates the differences between these three stages. Chemical evolution leads to much larger differences in molecular concentrations than can be achieved by selection without replication. However, chemical evolution is not open-ended, unlike biological evolution. The ability to undergo Darwinian evolution is often considered to be a defining feature of life. Here, I argue that chemical evolution, although Darwinian, does not quite constitute life, and that a good place to put the conceptual boundary between non-life and life is between chemical and biological evolution.

This is a preview of subscription content, log in to check access.

Access options

Buy single article

Instant unlimited access to the full article PDF.

US$ 39.95

Price includes VAT for USA

Subscribe to journal

Immediate online access to all issues from 2019. Subscription will auto renew annually.

US$ 199

This is the net price. Taxes to be calculated in checkout.

Fig. 1
Fig. 2
Fig. 3
Fig. 4


  1. Baross JA (2007) Evolution: a defining feature of life. In: Baross JA, Sullivan WT (eds) Planets and life: the emerging science of astrobiology. Cambridge University Press, Cambridge, pp 213–221

  2. Benner SA (2010) Defining life. Astrobiology 10:1021–1030

  3. Bull JJ, Meyers LA, Lachmann M (2005) Quasispecies made simple. PLoS Comput Biol 1:e61

  4. Chessari S, Luisi PL (2012) On evidence: the lack of evidence for prebiotic macromolecular synthesis. Orig Life Evol Biosph 42:412–415

  5. Cleland CE, Chyba CF (2007) Does ‘life’ have a definition? In: Baross JA, Sullivan WT (eds) Planets and life: the emerging science of astrobiology. Cambridge University Press, Cambridge, pp 119–131

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

  7. Damer B, Deamer D (2015) Coupled phases and combinatorial selection in fluctuating hydrothermal pools: a scenario to guide experimental approaches to the origin of cellular life. Life 5:872–887

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

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

  10. Eigen M, McCaskill J, Schuster P (1989) The molecular quasi-species. Adv Chem Phys 75:149–263

  11. Forsythe JG, Yu SS, Mamajanov I, Grover MA, Krishnamurthy R, Fernandez FM, Hud NV (2015) Ester-mediated amide bond formation driven by wet-dry cycles: a possible path to polypeptides on the prebiotic earth. Angew Chem Ind Ed 54:9871–9875

  12. Griesemer J (2000) The units of evolutionary transition. Selection 1:67–80

  13. Guttenberg N, Virgo N, Packard N (2017) The ‘selection first’ pathway to life. Presented at Astrobiology Science Conference

  14. Higgs PG (2012) Creating many identical copies of a macromolecular sequence. Orig Life Evol Biosph 42:416–419

  15. Higgs PG (2016) The effect of limited diffusion and wet-dry cycling on reversible polymerization reactions: implications for prebiotic synthesis of nucleic acids. Life 6:24

  16. Hud NV, Cafferty BJ, Krishnamurthy R, Williams LD (2013) The Origin of RNA and “My Grandfather’s Axe”. Chem and Biol 20:466–474

  17. Joyce GF (1994) Foreword. In Deamer D, Fleischaker G (eds) Origins of Life: The Central Concepts, Jones and Bartlett, Boston, pp xi-xii

  18. Joyce GF (2002) The antiquity of RNA-based evolution. Nature 418:214–221

  19. Kim YE, Higgs PG (2016) Co-operation between polymerases and nucleotide synthetases in the RNA world. PLoS Comput Biol 12:e1005161

  20. Koshland DE (2002) The seven pillars of life. Science 295:2215–2216

  21. Krishnamurthy R (2014) RNA as an emergent entity: an understanding gained through studying its non-functional alternatives. Synlett 25:1511–1517

  22. Krishnamurthy R (2015) On the emergence of RNA. Israel J Chem 55:837–850

  23. Leu K, Kervio E, Obermayer B, Turk-MacLeod R, Yuan C, Luevano J-M, Chen E, Gerland U, Richert C, Chen IA (2013) Cascade of reduced speed and accuracy after errors in enzyme-free copying of nucleic acid sequences. J Am Chem Soc 135:354–366

  24. Mamajanov I, MacDonald PJ, Ying J, Duncanson DM, Dowdy GR, Walker CA, Engelhart AE, Fernandez FM, Grover MA, Hud NV, Schork FJ (2014) Ester formation and hydrolysis during wet-dry cycles: generation of far-from-equilibrium polymers in a model prebiotic reaction. Macromolecules 47:1334–1343

  25. Markovitch O, Lancet D (2014) Multispecies population dynamics of prebitic compositional assemblies. J Theor Biol 357:26–34

  26. Mulkidjanian AY, Cherepanov DA, Galperin MY (2003) Survival of the fittest before the beginning of life: selection of the first oligonucleotide-like polymers by UV light. BMC Evol Biol 3:12

  27. Pross A (2012) What is Life? How Chemistry Becomes Biology. Oxford University Press, Oxford

  28. Ruiz-Mirazo K, Pereto J, Moreno A (2002) A universal definition of life: autonomy and open-ended evolution. Orig Life Evol Biosph 34:323–346

  29. Sardanyés J, Elena SF, Solé RV (2008) Simple quasispecies models for the survival-of-the-flattest effect: the role of space. J Theor Biol 250:560–568

  30. Segré D, Ben-Eli D, Lancet D (2000) Compositional genomes: prebiotic information transfer in mutually catalytic noncovalent assemblies. Proc Natl Acad Sci USA 97:4112–4117

  31. Shay JA, Huynh C, Higgs PG (2015) The origin and spread of a cooperative replicase in a prebiotic chemical system. J Theor Biol 364:249–259

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

  33. Szostak JW (2012a) Attempts to define life do not help to understand the origin of life. J Biomol Struct Dyn 29:599–600

  34. Szostak JW (2012b) The eightfold path to non-enzymatic RNA replication. J Syst Chem 3:2

  35. Trifonov EN (2011) Vocabulary of definitions of life suggests a definition. J Biomol Struct Dyn 29:259–264

  36. Tupper AS, Shi K, Higgs PG (2017) The role of templating in the emergence of RNA from the prebiotic chemical mixture. Life - submitted

  37. Walker SI, Grover MA, Hud NV (2012) Universal sequence replication, reversible polymerization and early functional biopolymers: a model for the initiation of prebiotic sequence evolution. PLoS ONE 7(4):e34166

  38. Wilke CO, Wang JL, Ofria C, Lenski RE, Adami C (2001) Evolution of digital organisms at high mutation rates leads to survival of the flattest. Nature 412:331–333

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

  40. Wu M, Higgs PG (2011) Comparison of the roles of nucleotide synthesis, polymerization, and recombination in the origin of autocatalytic sets of RNAs. Astrobiology 11:895–906

  41. Wu M, Higgs PG (2012) The origin of life is a spatially-localized stochastic transition. Biol Direct 7:42

Download references

Author information

Correspondence to Paul G. Higgs.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Higgs, P.G. Chemical Evolution and the Evolutionary Definition of Life. J Mol Evol 84, 225–235 (2017).

Download citation


  • Origin of life
  • Definition of life
  • Chemical evolution
  • RNA world
  • Quasispecies
  • Error threshold