The process by which chemistry can give rise to biology remains one of the biggest mysteries in contemporary science. The de novo synthesis and origin of life both require the functional integration of three key characteristics — replication, metabolism and compartmentalization — into a system that is maintained out of equilibrium and is capable of open-ended Darwinian evolution. This Review takes systems of self-replicating molecules as starting points and describes the steps necessary to integrate additional characteristics of life. We analyse how far experimental self-replicators have come in terms of Darwinian evolution. We also cover models of replicator communities that attempt to solve Eigen’s paradox, whereby accurate replication needs complex machinery yet obtaining such complex self-replicators through evolution requires accurate replication. Successful models rely on a collective metabolism and a way of (transient) compartmentalization, suggesting that the invention and integration of these two characteristics is driven by evolution. Despite our growing knowledge, there remain numerous key challenges that may be addressed by a combined theoretical and experimental approach.
Subscribe to Journal
Get full journal access for 1 year
only $8.25 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
Ruiz-Mirazo, K., Briones, C. & de la Escosura, A. Prebiotic systems chemistry: new perspectives for the origins of life. Chem. Rev. 114, 285–366 (2014).
Ludlow, R. F. & Otto, S. Systems chemistry. Chem. Soc. Rev. 37, 101–108 (2008).
Whitesides, G. M. & Ismagilov, R. F. Complexity in chemistry. Science 284, 89–92 (1999).
Ashkenasy, G., Hermans, T. M., Otto, S. & Taylor, A. F. Systems chemistry. Chem. Soc. Rev. 46, 2543–2554 (2017).
Gànti, T. The Principles of Life (Oxford Univ. Press, 2003).
Popa, R. Between Necessity and Probability: Searching for the Definition and Origin of Life (Springer, 2004).
Chodasewicz, K. Evolution, reproduction and definition of life. Theory Biosci. 133, 39–45 (2014).
Kosikova, T. & Philp, D. Exploring the emergence of complexity using synthetic replicators. Chem. Soc. Rev. 46, 7274–7305 (2017).
Duim, H. & Otto, S. Towards open-ended evolution in self-replicating molecular systems. Beilstein J. Org. Chem. 13, 1189–1203 (2017).
Bissette, A. J. & Fletcher, S. P. Mechanisms of autocatalysis. Angew. Chem. Int. Ed. 52, 12800–12826 (2013).
Patzke, V. & von Kiedrowski, G. Self replicating systems. Arkivoc 5, 293–310 (2007).
Le Vay, K., Weise, L. I., Libicher, K., Mascarenhas, J. & Mutschler, H. Templated self-replication in biomimetic systems. Adv. Biosyst. 3, 1800313 (2019).
Clixby, G. & Twyman, L. Self-replicating systems. Org. Biomol. Chem. 14, 4170–4184 (2016).
Robertson, A., Sinclair, A. J. & Philp, D. Minimal self-replicating systems. Chem. Soc. Rev. 29, 141–152 (2000).
Monnard, P.-A. & Walde, P. Current ideas about prebiological compartmentalization. Life 5, 1239–1263 (2015).
Beales, P. A., Ciani, B. & Mann, S. The artificial cell: biology-inspired compartmentalization of chemical function. Interface Focus. 8, 20180046 (2018).
Hanczyc, M. M., Fujikawa, S. M. & Szostak, J. W. Experimental models of primitive cellular compartments: encapsulation, growth, and division. Science 302, 618–622 (2003).
Bissette, A. J. & Fletcher, S. P. Novel applications of physical autocatalysis. Orig. Life Evol. Biosph. 45, 21–30 (2015).
Poudyal, R. R. et al. Template-directed RNA polymerization and enhanced ribozyme catalysis inside membraneless compartments formed by coacervates. Nat. Commun. 10, 490 (2019).
Stewart, J. E. The origins of life: the managed-metabolism hypothesis. Found. Sci. 24, 171–195 (2018).
Nghe, P. et al. Prebiotic network evolution: six key parameters. Mol. Biosyst. 11, 3206–3217 (2015).
Vasas, V., Fernando, C., Santos, M., Kauffman, S. & Szathmáry, E. Evolution before genes. Biol. Direct. 7, 1 (2012).
Ralser, M. An appeal to magic? The discovery of a non-enzymatic metabolism and its role in the origins of life. Biochem. J. 475, 2577–2592 (2018).
Muchowska, K. B., Varma, S. J. & Moran, J. Synthesis and breakdown of universal metabolic precursors promoted by iron. Nature 569, 104–107 (2019).
Engelhart, A. E., Adamala, K. P. & Szostak, J. W. A simple physical mechanism enables homeostasis in primitive cells. Nat. Chem. 8, 448–453 (2016).
Pross, A. What is Life? (Oxford Univ. Press, 2016).
Pascal, R., Pross, A. & Sutherland, J. D. Towards an evolutionary theory of the origin of life based on kinetics and thermodynamics. Open. Biol. 3, 130156 (2013).
Pross, A. Stability in chemistry and biology: life as a kinetic state of matter. Pure Appl. Chem. 77, 1905–1921 (2005).
Pross, A. & Pascal, R. A roadmap toward synthetic protolife. Synlett 28, 30–35 (2016).
Pross, A. & Pascal, R. How and why kinetics, thermodynamics, and chemistry induce the logic of biological evolution. Beilstein J. Org. Chem. 13, 665–674 (2017).
Maynard Smith, J. The Problems of Biology (Oxford Univ. Press, 1986).
Bissette, A. J., Odell, B. & Fletcher, S. P. Physical autocatalysis driven by a bond-forming thiol–ene reaction. Nat. Commun. 5, 4607 (2014).
Colomer, I., Morrow, S. M. & Fletcher, S. P. A transient self-assembling self-replicator. Nat. Commun. 9, 2239 (2018).
Walde, P., Wick, R., Fresta, M., Mangone, A. & Luisi, P. L. Autopoietic self-reproduction of fatty acid vesicles. J. Am. Chem. Soc. 116, 11649–11654 (1994).
Hardy, M. D. et al. Self-reproducing catalyst drives repeated phospholipid synthesis and membrane growth. Proc. Natl Acad. Sci. USA 112, 8187–8192 (2015).
Breslow, R. On the mechanism of the formose reaction. Tetrahedron Lett. 1, 22–26 (1959).
Orgel, L. E. Molecular replication. Nature 358, 203–209 (1992).
Maynard Smith, J. & Szathmáry, E. The Major Transitions in Evolution (Oxford Univ. Press, 1995).
Levin, S. R., Gandon, S. & West, S. A. The social coevolution hypothesis for the origin of enzymatic cooperation. Nat. Ecol. Evol. 4, 132–137 (2020).
Hordijk, W., Vaidya, N. & Lehman, N. Serial transfer can aid the evolution of autocatalytic sets. J. Syst. Chem. 5, 4 (2014).
Vaidya, N. et al. Spontaneous network formation among cooperative RNA replicators. Nature 491, 72–77 (2012).
Lifson, S. & Lifson, H. Coexistence and Darwinian selection among replicators: response to the preceding paper by Scheuring and Szathmary. J. Theor. Biol. 212, 107–109 (2001).
Blokhuis, A., Lacoste, D. & Gaspard, P. Reaction kinetics in open reactors and serial transfers between closed reactors. J. Chem. Phys. 148, 144902 (2018).
Eigen, M. Selforganization of matter and the evolution of biological macromolecules. Naturwissenschaften 58, 465–523 (1971).
Eigen, M. & Winkler-Oswatitsch, R. Steps Towards Life (Oxford Univ. Press, 1992).
Szathmáry, E. & Gladkih, I. Sub-exponential growth and coexistence of non-enzymatically replicating templates. J. Theor. Biol. 138, 55–58 (1989).
von Kiedrowski, G. Minimal replicator theory I.: parabolic versus exponential growth. Bioorg. Chem. Front. 3, 113–146 (1993).
Luisi, P. L. The Emergence of Life: From Chemical Origins to Synthetic Biology (Cambridge Univ. Press, 2006).
Károlyi, G., Scheuring, I. & Czárán, T. Metabolic network dynamics in open chaotic flow. Chaos 12, 460–469 (2002).
Károlyi, G., Péntek, Á., Scheuring, I., Tél, T. & Toroczkai, Z. Chaotic flow: the physics of species coexistence. Proc. Natl Acad. Sci. USA 97, 13661–13665 (2000).
Könnyű, B. & Czárán, T. Spatial aspects of prebiotic replicator coexistence and community stability in a surface-bound RNA world model. BMC Evol. Biol. 13, 204 (2013).
Wilson, D. S. A theory of group selection. Proc. Natl Acad. Sci. USA 72, 143–146 (1975).
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).
Rubinov, B., Wagner, N., Rapaport, H. & Ashkenasy, G. Self-replicating amphiphilic β-sheet peptides. Angew. Chem. Int. Ed. 48, 6683–6686 (2009).
Colomb-Delsuc, M., Mattia, E., Sadownik, J. W. & Otto, S. Exponential self-replication enabled through a fibre elongation/breakage mechanism. Nat. Commun. 6, 7427 (2015).
Ruiz-Mirazo, K., Peretó, J. & Moreno, A. A universal definition of life: autonomy and open-ended evolution. Orig. Life Evol. Biosphere 34, 323–346 (2004).
de Vladar, H. P., Santos, M. & Szathmáry, E. Grand views of evolution. Trends Ecol. Evol. 32, 324–334 (2017).
Szathmáry, E. Life: in search of the simplest cell. Nature 433, 469–470 (2005).
Walde, P. Prebiotic Chemistry (Springer, 2005).
Santiago, G. M., Liu, K., Browne, W. R. & Otto, S. Emergence of light-driven protometabolism upon recruitment of a photocatalytic cofactor by a self-replicator. Nat. Chem. https://doi.org/10.1038/s41557-020-0494-4 (2020).
Ottelé, J. O., Hussain, A. S., Mayer, C. & Otto, S. Chance emergence of catalytic activity and promiscuity in a self-replicator. Nat. Catal. https://doi.org/10.1038/s41929-020-0463-8 (2020).
Kurihara, K. et al. Self-reproduction of supramolecular giant vesicles combined with the amplification of encapsulated DNA. Nat. Chem. 3, 775–781 (2011).
Maynard Smith, J. Hypercycles and the origin of life. Nature 280, 445–446 (1979).
Boerlijst, M. C. & Hogeweg, P. Spiral wave structure in pre-biotic evolution: hypercycles stable against parasites. Phys. D. 48, 17–28 (1991).
Michod, R. Population biology of the first replicators: the origin of genotype, phenotype and organism. Am. Zool. 23, 5–14 (1983).
Szathmáry, E. Natural selection and dynamical coexistence of defective and complementing virus segments. J. Theor. Biol. 157, 383–406 (1992).
Czárán, T. & Szathmáry, E. Coexistence of Replicators in Prebiotic Evolution (Cambridge Univ. Press, 2000).
Czárán, T., Könnyű, B. & Szathmáry, E. Metabolically coupled replicator systems: overview of an RNA-world model concept of prebiotic evolution on mineral surfaces. J. Theor. Biol. 381, 39–54 (2015).
Szilágyi, A., Könnyű, B. & Czárán, T. Dynamics and stability in prebiotic information integration: an RNA world model from first principles. Sci. Rep. 10, 51 (2020).
Szabó, P., Scheuring, I., Czárán, T. & Szathmáry, E. In silico simulations reveal that replicators with limited dispersal evolve towards higher efficiency and fidelity. Nature 420, 340–343 (2002).
Luther, A., Brandsch, R. & von Kiedrowski, G. Surface-promoted replication and exponential amplification of DNA analogues. Nature 396, 245–248 (1998).
Szathmáry, E. & Demeter, L. Group selection of early replicators and the origin of life. J. Theor. Biol. 128, 463–486 (1987).
Grey, D., Hutson, V. & Szathmáry, E. A re-examination of the stochastic corrector model. Proc. R. Soc. Lond. 262, 29–35 (1995).
Damuth, J. & Heisler, I. L. Alternative formulations of multilevel selection. Biol. Philos. 3, 407–430 (1988).
Zintzaras, E., Santos, M. & Szathmáry, E. “Living” under the challenge of information decay: the stochastic corrector model versus hypercycles. J. Theor. Biol. 217, 167–181 (2002).
Szilágyi, A., Kun, Á. & Szathmáry, E. Early evolution of efficient enzymes and genome organization. Biol. Direct. 7, 38 (2012).
Maynard Smith, J. & Szathmáry, E. The origin of the chromosome I. Selection for linkage. J. Theor. Biol. 164, 437–446 (1993).
Szilágyi, A., Kovács, P. V., Szathmáry, E. & Santos, M. Evolution of linkage and genome expansion in protocells. Preprint at bioRxiv https://doi.org/10.1101/746495 (2019).
Vig-Milkovics, Z., Zachar, I., Kun, Á., Szilágyi, A. & Szathmáry, E. Moderate sex between protocells can balance between a decrease in assortment load and an increase in parasite spread. J. Theor. Biol. 462, 304–310 (2019).
Hordijk, W., Steel, M. & Kauffman, S. A. Molecular diversity required for the formation of autocatalytic sets. Life 9, 23 (2019).
Ashkenasy, G., Jagasia, R., Yadav, M. & Ghadiri, M. R. Design of a directed molecular network. Proc. Natl Acad. Sci. USA 101, 10872–10877 (2004).
Szathmáry, E. A classification of replicators and λ-calculus models of biological organization. Proc. Biol. Sci. 260, 279–286 (1995).
Kun, Á., Papp, B. & Száthmary, E. Computational identification of obligatorily autocatalytic replicators embedded in metabolic networks. Genome Biol. 9, R51 (2008).
Muchowska, K. B. et al. Metals promote sequences of the reverse Krebs cycle. Nat. Ecol. Evol. 1, 1716–1721 (2017).
Sievers, D. & von Kiedrowski, G. Self-replication of hexadeoxynucleotide analogues: autocatalysis versus cross-catalysis. Chem. Eur. J. 4, 629–641 (1998).
Yao, S., Ghosh, I., Zutshi, R. & Chmielewski, J. Selective amplification by auto- and cross-catalysis in a replicating peptide system. Nature 396, 447–450 (1998).
Kauffman, S. A. Cellular homeostasis, epigenesis and replication in randomly aggregated macromolecular systems. J. Cybern. 1, 71–96 (1971).
Kauffman, S. A. Autocatalytic sets of proteins. J. Theor. Biol. 119, 1–24 (1986).
Mossel, E. & Steel, M. Random biochemical networks: the probability of self-sustaining autocatalysis. J. Theor. Biol. 233, 327–336 (2005).
Kauffman, S. A. The Origins of Order (Oxford Univ. Press, 1993).
Issac, R., Ham, Y.-W. & Chmielewski, J. The design of self-replicating helical peptides. Curr. Opin. Struc. Biol. 11, 458–463 (2001).
Li, X. & Chmielewski, J. Peptide self-replication enhanced by a proline kink. J. Am. Chem. Soc. 125, 11820–11821 (2003).
Issac, R. & Chmielewski, J. Approaching exponential growth with a self-replicating peptide. J. Am. Chem. Soc. 124, 6808–6809 (2002).
Wang, B. & Sutherland, I. O. Self-replication in a Diels–Alder reaction. Chem. Commun. 16, 1495–1496 (1997).
Robertson, M. P. & Joyce, G. F. Highly efficient self-replicating RNA enzymes. Chem. Biol. 21, 238–245 (2014).
Nowak, P., Colomb-Delsuc, M., Otto, S. & Li, J. Template-triggered emergence of a self-replicator from a dynamic combinatorial library. J. Am. Chem. Soc. 137, 10965–10969 (2015).
Komáromy, D. et al. Self-assembly can direct dynamic covalent bond formation toward diversity or specificity. J. Am. Chem. Soc. 139, 6234–6241 (2017).
Simmel, F. C. Nanostructure evolution. Nat. Mater. 16, 974–976 (2017).
Eigen, M. & Schuster, P. The hypercycle. A principle of natural self-organisation Part A: emergence of the hypercycle. Naturwissenschaften 64, 541–565 (1977).
Wagner, N., Mukherjee, R., Maity, I., Peacock-Lopez, E. & Ashkenasy, G. Bistability and bifurcation in minimal self-replication and nonenzymatic catalytic networks. ChemPhysChem 18, 1842–1850 (2017).
Mukherjee, R., Cohen-Luria, R., Wagner, N. & Ashkenasy, G. A bistable switch in dynamic thiodepsipeptide folding and template-directed ligation. Angew. Chem. Int. Ed. 54, 12452–12456 (2015).
Severin, K., Lee, D. H., Martinez, J. A., Vieth, M. & Ghadiri, M. R. Dynamic error correction in autocatalytic peptide networks. Angew. Chem. Int. Ed. 37, 126–128 (1998).
Nanda, J. et al. Emergence of native peptide sequences in prebiotic replication networks. Nat. Commun. 8, 434 (2017).
Sadownik, J. W., Mattia, E., Nowak, P. & Otto, S. Diversification of self-replicating molecules. Nat. Chem. 8, 264–269 (2016).
Lincoln, T. A. & Joyce, G. F. Self-sustained replication of an RNA enzyme. Science 323, 1229–1232 (2009).
Mills, D. R., Peterson, R. E. & Spiegelman, S. An extracellular Darwinian experiment with a self-duplicating nucleic acid molecule. Proc. Natl Acad. Sci. USA 58, 217–224 (1967).
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).
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).
Jayathilaka, T. S. & Lehman, N. Spontaneous covalent self-assembly of the Azoarcus ribozyme from five fragments. ChemBioChem 19, 217–220 (2018).
Lee, D. H., Severin, K. & Ghadiri, M. R. Autocatalytic networks: the transition from molecular self-replication to molecular ecosystems. Curr. Opin. Chem. Biol. 1, 491–496 (1997).
Mizuuchi, R. & Lehman, N. Limited sequence diversity within a population supports prebiotic RNA reproduction. Life 9, 20 (2019).
Arsène, S., Ameta, S., Lehman, N., Griffiths, A. D. & Nghe, P. Coupled catabolism and anabolism in autocatalytic RNA sets. Nucleic Acids Res. 46, 9660–9666 (2018).
Mathis, C., Ramprasad, S. N., Walker, S. I. & Lehman, N. Prebiotic RNA network formation: a taxonomy of molecular cooperation. Life 7, 38 (2017).
Yeates, J. A. M., Nghe, P. & Lehman, N. Topological and thermodynamic factors that influence the evolution of small networks of catalytic RNA species. RNA 23, 1088–1096 (2017).
Wächtershäuser, G. Vitalysts and Virulysts: A Theory of Self-Expanding Reproduction (Columbia Univ. Press, 1994).
Kosikova, T. & Philp, D. Two synthetic replicators compete to process a dynamic reagent pool. J. Am. Chem. Soc. 141, 3059–3072 (2019).
Bottero, I., Huck, J., Kosikova, T. & Philp, D. A synthetic replicator drives a propagating reaction–diffusion front. J. Am. Chem. Soc. 138, 6723–6726 (2016).
Sadownik, J. W., Kosikova, T. & Philp, D. Generating system-level responses from a network of simple synthetic replicators. J. Am. Chem. Soc. 139, 17565–17573 (2017).
Altay, M., Altay, Y. & Otto, S. Parasitic behavior of self-replicating molecules. Angew. Chem. Int. Ed. 57, 10564–10568 (2018).
Lee, D. H., Severin, K., Yokobayashi, Y. & Ghadiri, M. R. Emergence of symbiosis in peptide self-replication through a hypercyclic network. Nature 390, 591–594 (1997).
Szathmáry, E. On the propagation of a conceptual error concerning hypercycles and cooperation. J. Syst. Chem. 4, 1 (2013).
Kamioka, S., Ajami, D. & Rebek Jr, J. Autocatalysis and organocatalysis with synthetic structures. Proc. Natl Acad. Sci. USA 107, 541–544 (2010).
Urabe, H. et al. Compartmentalization in a water-in-oil emulsion repressed the spontaneous amplification of RNA by Qβ replicase. Biochemistry 49, 1809–1813 (2010).
Bansho, Y., Furubayashi, T., Ichihashi, N. & Yomo, T. Host–parasite oscillation dynamics and evolution in a compartmentalized RNA replication system. Proc. Natl Acad. Sci. USA 113, 4045–4050 (2016).
Matsumura, S. et al. Transient compartmentalization of RNA replicators prevents extinction due to parasites. Science 354, 1293–1296 (2016).
Yoshiyama, T., Ichii, T., Yomo, T. & Ichihashi, N. Automated in vitro evolution of a translation-coupled RNA replication system in a droplet flow reactor. Sci. Rep. 8, 11867 (2018).
Liu, B. et al. Spontaneous emergence of self-replicating molecules containing nucleobases and amino acids. J. Am. Chem. Soc. 142, 4148–4192 (2020).
Tjivikua, T., Ballester, P. & Rebek Jr, J. A self-replicating system. J. Am. Chem. Soc. 112, 1249–1250 (1990).
Quayle, J. M., Slawin, A. M. Z. & Philp, D. A structurally simple minimal self-replicating system. Tetrahedron Lett. 43, 7229–7233 (2002).
von Kiedrowski, G. A self-replicating hexadeoxynucleotide. Angew. Chem. Int. Ed. 25, 932–935 (1986).
Paul, N. & Joyce, G. F. A self-replicating ligase ribozyme. Proc. Natl Acad. Sci. USA 99, 12733–12740 (2002).
Hayden, E. J. & Lehman, N. Self-assembly of a group I intron from inactive oligonucleotide fragments. Chem. Biol. 13, 909–918 (2006).
Draper, W. E., Hayden, E. J. & Lehman, N. Mechanisms of covalent self-assembly of the Azoarcus ribozyme from four fragment oligonucleotides. Nucleic Acids Res. 36, 520–531 (2008).
Lee, D. H., Granja, J. R., Martinez, J. A., Severin, K. & Ghadiri, M. R. A self-replicating peptide. Nature 382, 525–528 (1996).
Rubinov, B. et al. Transient fibril structures facilitating nonenzymatic self-replication. ACS Nano 6, 7893–7901 (2012).
Otto, S. et al. Mechanosensitive self-replication driven by self-organization. Science 327, 1502–1506 (2010).
Malakoutikhah, M. et al. Uncovering the selection criteria for the emergence of multi-building-block replicators from dynamic combinatorial libraries. J. Am. Chem. Soc. 135, 18406–18417 (2013).
Hofbauer, J. A difference equation model for the hypercycle. SIAM J. Appl. Math. 44, 762–772 (1984).
Guillamon, A., Fontich, E. & Sardanyés, J. Bifurcations analysis of oscillating hypercycles. J. Theor. Biol. 387, 23–30 (2015).
Hofbauer, J., Mallet-Paret, J. & Smith, H. L. Stable periodic solutions for the hypercycle system. J. Dynam. Differ. Equat. 3, 423–436 (1991).
Stadler, P. F. & Nuño, J. C. The influence of mutation on autocatalytic reaction networks. Math. Biosci. 122, 127–160 (1994).
Bresch, C., Niesert, U. & Harnasch, D. Hypercycles, parasites and packages. J. Theor. Biol. 85, 399–405 (1980).
Boerlijst, M. C. & Hogeweg, P. Selfstructuring and Selection: Spiral Waves as a Substrate for Evolution (Addison-Wesley, 1991).
Kim, P.-J. & Jeong, H. Spatio-temporal dynamics in the origin of genetic information. Phys. D. 203, 88–99 (2005).
Szilágyi, A. et al. Ecology and evolution in the RNA world: dynamics and stability of prebiotic replicator systems. Life 7, 48 (2017).
Könnyű, B. & Czárán, T. Specialization of early replicators in the metabolic replicator model system. Orig. Life Evol. Biosphere 39, 339–340 (2009).
Hofbauer, J. & Sigmund, K. Evolutionary Games and Population Dynamics (Cambridge Univ. Press, 1998).
Yeates, J. A. M., Hilbe, C., Zwick, M., Nowak, M. A. & Lehman, N. Dynamics of prebiotic RNA reproduction illuminated by chemical game theory. Proc. Natl Acad. Sci. USA 113, 5030–5035 (2016).
The authors thank A. Pross for discussions leading to the definition of dynamic kinetic stability. They are grateful for the EU Attract program (EmLife), the ERC (Advanced Grant ‘Towards de-novo life’; ToDL 741774), the Dutch Ministry of Education, Culture and Science (Gravitation program 024.001.035) and the National Research, Development and Innovation Office (NKFIH, Hungary) under grant numbers GINOP-2.3.2-15-2016-00057 and K119347, and the Volkswagen Stiftung initiative ‘Leben? — Ein neuer Blick der Naturwissenschaften auf die grundlegenden Prinzipien des Lebens’ under the project ‘A Unified Model of Recombination in Life’ for financial support. A. Szilágyi was supported by the Bolyai János Research Fellowship of the Hungarian Academy of Sciences.
The authors declare no competing interests.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
- Systems chemistry
The study of properties that emerge from mixtures of interacting molecules. One of the key foci is the analysis and synthesis of diverse autocatalytic systems and their possible couplings.
Chemical processes that form the constituents of a living system from (often simple) raw materials (the food set) and connect the internal maintenance of the system to an external energy source.
- Darwinian evolution
Evolution by natural selection that requires units that multiply and have heredity and variability. There should be hereditary traits that affect the chance of reproduction and/or survival of the units.
A system that enables spatial gradients (whereas chemists often consider bulk, well-stirred systems). Passive compartmentalization can be provided by absorptive surface and rock pores. Active compartmentalization rests on boundaries (such as membranes created through autopoiesis).
- Out of equilibrium
Any state that is not at equilibrium.
- Dynamic kinetic stability
A persistent state of an open chemical system resulting from a cyclic process of formation (replicative or otherwise) and destruction, occurring effectively irreversibly (that is, formation and destruction reactions are kinetically directed and not each other’s microscopic reverse), driven by continual material and/or energy input.
The ability of a system to autonomously catalyse the formation of copies of itself, such that information contained in the molecules that constitute the system is transferred to the next generation.
- Exponential replication
An autocatalytic process with constant per-capita growth. Exponential replication leads to infinite concentration in infinite time. In competition, it entails survival of the fittest.
A complex process in which a system is able to produce more of itself and its constituent molecules.
The weighted distribution of mutants centred around one or several master sequences in a mutation–selection balance. The quasi-species is the target of selection in a system of replicating individuals who replicate without cooperating with one another.
- Competitive exclusion principle
The principle that, in a replication–destruction regime harbouring self-replicators capable of exponential growth that compete for the same precursors (from which they replicate), one replicator will drive all others to extinction.
- Eigen’s paradox
The paradox that accurate replication needs complex machinery, yet obtaining such complex self-replicators through evolution requires sufficiently accurate replication.
- Open-ended evolution
A process whereby Darwinian replicator evolution proceeds indefinitely in a non-trivial manner. It may come in three forms: weak, strong and ultimate. In the weak form, novel phenotypes (not seen before, perhaps a new form of beak on a bird) arise indefinitely. The strong form requires evolutionary innovations, such as a novel catalytic or motor activity. The ultimate form allows for a major transition to occur, with the emergence of higher units of evolution from lower ones, such as reproducing protocells from replicating molecules.
The process in which one replicator consumes another (the prey) for its own replication. The predator population benefits, and the prey population suffers.
An ecological coupling between two populations from which both benefit. Analogous to a two-membered hypercycle.
A replicator set in which the autocatalytic replication of each member is heterocatalytically aided by another member conforming to cyclic topology.
- Error threshold
The critical value of the mutation rate, above which errors accumulate and soon lead to the complete loss of information (error catastrophe) upon multiple rounds of replication. Stable selection requires that the error rate lies below the error threshold.
Replicators that take help from another without paying back. The helper pays a cost in terms of fitness by maintaining its helping capacity. Saving this cost, the parasite has a replicative advantage.
An RNA molecule that can act as a catalyst.
- Collectively autocatalytic set
A reaction network in which no member is itself autocatalytic but the members catalyse the production or formation (but not the replication) of other members of the set. The set is collectively autocatalytic if the formation of every member is catalysed by at least one other member of the set.
- Parabolic replication
Replication that is slower than exponential because the per-capita growth rate decreases with increasing replicator concentration.
The propensity of an informational molecule to join a collectively autocatalytic set rather than replicating itself directly.
- Dynamic combinatorial library
A set of continuously interconverting oligomeric molecules made by linking building blocks together through a reversible reaction.
About this article
Cite this article
Adamski, P., Eleveld, M., Sood, A. et al. From self-replication to replicator systems en route to de novo life. Nat Rev Chem 4, 386–403 (2020). https://doi.org/10.1038/s41570-020-0196-x
Probing self-regeneration of essential protein factors required for in vitro translation activity by serial transfer
Chemical Communications (2020)