Skip to main content
SpringerLink
Log in

Mutations and Lethality in Simulated Prebiotic Networks

  • Published:
Journal of Molecular Evolution Aims and scope Submit manuscript

Abstract

The Graded Autocatalysis Replication Domain (GARD) model describes an origin of life scenario which involves non-covalent compositional assemblies, made of monomeric mutually catalytic molecules. GARD constitutes an alternative to informational biopolymers as a mechanism of primordial inheritance. In the present work, we examined the effect of mutations, one of the most fundamental mechanisms for evolution, in the context of the networks of mutual interaction within GARD prebiotic assemblies. We performed a systematic analysis analogous to single and double gene deletions within GARD. While most deletions have only a small effect on both growth rate and molecular composition of the assemblies, ~10% of the deletions caused lethality, or sometimes showed enhanced fitness. Analysis of 14 different network properties on 2,000 different GARD networks indicated that lethality usually takes place when the deleted node has a high molecular count, or when it is a catalyst for such node. A correlation was also found between lethality and node degree centrality, similar to what is seen in real biological networks. Addressing double knockout mutations, our results demonstrate the occurrence of both synthetic lethality and extragenic suppression within GARD networks, and convey an attempt to correlate synthetic lethality to network node-pair properties. The analyses presented help establish GARD as a workable alternative prebiotic scenario, suggesting that life may have begun with large molecular networks of low fidelity, that later underwent evolutionary compaction and fidelity augmentation.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10

Similar content being viewed by others

References

  • Alm E, Arkin AP (2003) Biological networks. Curr Opin Struct Biol 13:193–202

    Article  CAS  PubMed  Google Scholar 

  • Bachmann PA, Luisi PL, Lang J (1992) Autocatalytic self-replicating micelles as models for prebiotic structures. Nature 357:57–59

    Article  CAS  Google Scholar 

  • Bagley RJ, Farmer DJ (1991) Spontaneous emergence of a metabolism. In: Langton CG, Taylor C, Farmer JD, Rasmussen S (eds) Artificial life II. Addison-Wesley, Redwood City, pp 93–140

    Google Scholar 

  • Barabasi AL, Oltvai ZN (2004) Network biology: understanding the cell’s functional organization. Nat Rev Genet 5:101–113

    Article  CAS  PubMed  Google Scholar 

  • Barandiaran X, Ruiz-Mirazo K (2008) Modelling autonomy: simulating the essence of life and cognition. Introduction. Biosystems 91:295–304

    Article  PubMed  Google Scholar 

  • Benko G, Flamm C, Stadler PF (2003) A graph-based toy model of chemistry. J Chem Inf Comput Sci 43:1085–1093

    PubMed  Google Scholar 

  • Boone C, Bussey H, Andrews BJ (2007) Exploring genetic interactions and networks with yeast. Nat Rev Genet 8:437–449

    Article  CAS  PubMed  Google Scholar 

  • de Visser JA, Hermisson J, Wagner GP, Ancel Meyers L, Bagheri-Chaichian H, Blanchard JL, Chao L, Cheverud JM, Elena SF, Fontana W, Gibson G, Hansen TF, Krakauer D, Lewontin RC, Ofria C, Rice SH, von Dassow G, Wagner A, Whitlock MC (2003) Perspective: evolution and detection of genetic robustness. Evolution 57:1959–1972

    Article  PubMed  Google Scholar 

  • DeLuna A, Vetsigian K, Shoresh N, Hegreness M, Colon-Gonzalez M, Chao S, Kishony R (2008) Exposing the fitness contribution of duplicated genes. Nat Genet 40:676–681

    Article  CAS  PubMed  Google Scholar 

  • Dyson FJ (1982) A model for the origin of life. J Mol Evol 18:344–350

    Article  CAS  PubMed  Google Scholar 

  • Dyson FJ (1999) Origins of life. Cambridge University Press, Cambridge, UK

    Google Scholar 

  • Etxeberria A, Ruiz-Mirazo K (2009) The challenging biology of transients. A view from the perspective of autonomy. EMBO Rep 10(Suppl 1):S33–S36

    Article  CAS  PubMed  Google Scholar 

  • Farmer JD, Kauffman SA, Packard NH (1986) Autocatalytic replication of polymers. Physica 22D:50–67

    CAS  Google Scholar 

  • Fox SW (1991) Synthesis of life in the lab? Defining a protoliving system. Q Rev Biol 66:181–185

    Article  CAS  PubMed  Google Scholar 

  • Gesteland RF, Cech TR, Atkins JF (1999) The RNA world, 2nd edn. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York

    Google Scholar 

  • Gesteland RF, Cech TR, Atkins JF (2000) The RNA world. Cold Spring Harbor Laboratory, Cold Spring Harbor

    Google Scholar 

  • Giaever G, Chu AM, Ni L, Connelly C, Riles L, Veronneau S, Dow S, Lucau-Danila A, Anderson K, Andre B, Arkin AP, Astromoff A, El-Bakkoury M, Bangham R, Benito R, Brachat S, Campanaro S, Curtiss M, Davis K, Deutschbauer A, Entian KD, Flaherty P, Foury F, Garfinkel DJ, Gerstein M, Gotte D, Guldener U, Hegemann JH, Hempel S, Herman Z, Jaramillo DF, Kelly DE, Kelly SL, Kotter P, LaBonte D, Lamb DC, Lan N, Liang H, Liao H, Liu L, Luo C, Lussier M, Mao R, Menard P, Ooi SL, Revuelta JL, Roberts CJ, Rose M, Ross-Macdonald P, Scherens B, Schimmack G, Shafer B, Shoemaker DD, Sookhai-Mahadeo S, Storms RK, Strathern JN, Valle G, Voet M, Volckaert G, Wang CY, Ward TR, Wilhelmy J, Winzeler EA, Yang Y, Yen G, Youngman E, Yu K, Bussey H, Boeke JD, Snyder M, Philippsen P, Davis RW, Johnston M (2002) Functional profiling of the Saccharomyces cerevisiae genome. Nature 418:387–391

    Article  CAS  PubMed  Google Scholar 

  • Gilbert W (1986) The RNA world. Nature 319:618

    Article  Google Scholar 

  • Gillespie DT (2001) Approximate accelerated stochastic simulation of chemically reacting systems. J Chem Phys 115:1716–1733

    Article  CAS  Google Scholar 

  • Hartman JLt, Garvik B, Hartwell L (2001) Principles for the buffering of genetic variation. Science 291:1001–1004

    Article  CAS  PubMed  Google Scholar 

  • He X, Zhang J (2006) Why do hubs tend to be essential in protein networks? PLoS Genet 2:e88

    Article  PubMed  CAS  Google Scholar 

  • Iglehart JD, Silver DP (2009) Synthetic lethality—a new direction in cancer-drug development. N Engl J Med 361:189–191

    Article  CAS  PubMed  Google Scholar 

  • Jain S, Krishna S (2001) A model for the emergence of cooperation, interdependence, and Structure in evolving networks. Proc Natl Acad Sci USA 98:543–547

    Article  CAS  PubMed  Google Scholar 

  • Jain S, Krishna S (2002) Large extinctions in an evolutionary model: the role of innovation and keystone species. Proc Natl Acad Sci USA 99:2055–2060

    Article  CAS  PubMed  Google Scholar 

  • Jeong H, Tombor B, Albert R, Oltvai ZN, Barabasi AL (2000) The large-scale organization of metabolic networks. Nature 407:651–654

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Kaelin WG Jr (2005) The concept of synthetic lethality in the context of anticancer therapy. Nat Rev Cancer 5:689–698

    Article  CAS  PubMed  Google Scholar 

  • Kaneko K (2002) Kinetic origin of heredity in a replicating system with a catalytic network. J Biol Phys 28:781–792

    Article  CAS  Google Scholar 

  • Kaneko K (2003) Recursiveness, switching, and fluctuations in a replicating catalytic network. Phys Rev E Stat Nonlin Soft Matter Phys 68:031909

    PubMed  Google Scholar 

  • Kauffman SA (1993) The origins of order—self-organization and selection in evolution. Oxford University Press, New York

    Google Scholar 

  • Kennedy RD, D’Andrea AD (2006) DNA repair pathways in clinical practice: lessons from pediatric cancer susceptibility syndromes. J Clin Oncol 24:3799–3808

    Article  CAS  PubMed  Google Scholar 

  • Lancet D, Sadovsky E, Seidemann E (1993) Probability model for molecular recognition in biological receptor repertoires—significance to the olfactory system. Proc Natl Acad Sci USA 90:3715–3719

    Article  CAS  PubMed  Google Scholar 

  • Lancet D, Kedem O, Pilpel Y (1994) Emergence of order in small autocatalytic sets maintained far from equilibrium—application of a probabilistic receptor affinity distribution (RAD) model. Berichte Der Bunsen-Gesellschaft-Phys Chem Chem Phys 98:1166–1169

    CAS  Google Scholar 

  • Lee DH, Granja JR, Martinez JA, Severin K, Ghadiri MR (1996) A self-replicating peptide. Nature 382:525–528

    Article  CAS  PubMed  Google Scholar 

  • Lu C, King RD (2009) An investigation into the population abundance distribution of mRNAs, proteins, and metabolites in biological systems. Bioinformatics 25:2020–2027

    Article  CAS  PubMed  Google Scholar 

  • Luisi PL (2004) Introduction to COST27, special issue. Orig Life Evol Biosph 34:1–2

    Article  Google Scholar 

  • Luisi PL, Walde P, Oberholzer T (1999) Lipid vesicles as possible intermediates in the origin of life. Curr Opin Colloid Interface Sci 4:33–39

    Article  CAS  Google Scholar 

  • Monk NA (2003) Unravelling nature’s networks. Biochem Soc Trans 31:1457–1461

    Article  CAS  PubMed  Google Scholar 

  • Monnard PA, Kanavarioti A, Deamer DW (2003) Eutectic phase polymerization of activated ribonucleotide mixtures yields quasi-equimolar incorporation of purine and pyrimidine nucleobases. J Am Chem Soc 125:13734–13740

    Article  CAS  PubMed  Google Scholar 

  • Morowitz HJ (1992) The beginnings of cellular life. Yale University Press, New Haven

    Google Scholar 

  • Naveh B, Sipper M, Lancet D, Shenhav B (2004) Lipidia: an artificial chemistry of self-replicating assemblies of lipid-like molecules. In: Proceeding of the 9th international conference on the simulation and synthesis of living systems (ALIFE9), Boston, Massachusetts, pp 501–506

  • Newman MEJ (2003) The structure and function of complex networks. Siam Rev 45:167–256

    Article  Google Scholar 

  • Orgel LE (1998) The origin of life—a review of facts and speculations. TIBS 23:491–495

    CAS  PubMed  Google Scholar 

  • Pal C, Papp B, Hurst LD (2003) Genomic function: rate of evolution and gene dispensability. Nature 421:496–497 discussion 497–498

    Article  CAS  PubMed  Google Scholar 

  • Platzer A, Perco P, Lukas A, Mayer B (2007) Characterization of protein-interaction networks in tumors. BMC Bioinform 8:224

    Article  CAS  Google Scholar 

  • Rodrigues FA, Costa Lda F (2009) Protein lethality investigated in terms of long range dynamical interactions. Mol Biosyst 5:385–390

    Article  CAS  PubMed  Google Scholar 

  • Rosenwald S, Kafri R, Lancet D (2002) Test of a statistical model for molecular recognition in biological repertoires. J Theor Biol 216:327–336

    Article  CAS  PubMed  Google Scholar 

  • Ruiz-Mirazo K, Mavelli F (2007) Question 7: modelling minimal ‘lipid-peptide’ cells. Orig Life Evol Biosph 37:433–437

    Article  CAS  PubMed  Google Scholar 

  • Ruiz-Mirazo K, Mavelli F (2008) On the way towards ‘basic autonomous agents’: stochastic simulations of minimal lipid-peptide cells. Biosystems 91:374–387

    Article  CAS  PubMed  Google Scholar 

  • Ruiz-Mirazo K, Moreno A (2004) Basic autonomy as a fundamental step in the synthesis of life. Artif Life 10:235–259

    Article  PubMed  Google Scholar 

  • Segre D, Lancet D (2000) Composing life. EMBO Rep 1:217–222

    Article  CAS  PubMed  Google Scholar 

  • Segre D, Lancet D, Kedem O, Pilpel Y (1998a) Graded autocatalysis replication domain (GARD): kinetic analysis of self-replication in mutually catalytic sets. Orig Life Evol Biosph 28:501–514

    Article  CAS  Google Scholar 

  • Segre D, Pilpel Y, Lancet D (1998b) Mutual catalysis in sets of prebiotic organic molecules: evolution through computer simulated chemical kinetics. Physica A 249:558–564

    Article  CAS  Google Scholar 

  • Segre 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

    Article  CAS  PubMed  Google Scholar 

  • Segre D, Ben-Eli D, Deamer DW, Lancet D (2001) The lipid world. Orig Life Evol Biosph 31:119–145

    Article  CAS  PubMed  Google Scholar 

  • Segre D, Vitkup D, Church GM (2002) Analysis of optimality in natural and perturbed metabolic networks. Proc Natl Acad Sci USA 99:15112–15117

    Article  CAS  PubMed  Google Scholar 

  • Shapiro R (2006) Small molecule interactions were central to the origin of life. Q Rev Biol 81:105–125

    Article  PubMed  Google Scholar 

  • Shenhav B, Segre D, Lancet D (2003) Mesobiotic emergence: molecular and ensemble complexity in early evolution. Adv Complex Syst 6:15–35

    Article  Google Scholar 

  • Shenhav B, Kafri R, Lancet D (2004) Graded artificial chemistry in restricted boundaries. In: Proceedings of 9th international conference on the simulation and synthesis of living systems (ALIFE9). Boston, Massachusetts, USA

  • Shenhav B, Bar-Even A, Kafri R, Lancet D (2005a) Polymer GARD: computer simulation of covalent bond formation in reproducing molecular assemblies. Orig Life Evol Biosph 35:111–133

    Article  CAS  PubMed  Google Scholar 

  • Shenhav B, Solomon A, Lancet D, Kafri R (2005b) Early systems biology and prebiotic networks. Trans Comput Syst Biol LNCS 3380:14–27

    Article  CAS  Google Scholar 

  • Shenhav B, Oz A, Lancet D (2007) Coevolution of compositional protocells and their environment. Philos Trans Roy Soc B 362:1813–1819

    Article  CAS  Google Scholar 

  • Siegal ML, Promislow DE, Bergman A (2007) Functional and evolutionary inference in gene networks: does topology matter? Genetica 129:83–103

    Article  CAS  PubMed  Google Scholar 

  • Stadler PF (1991) Dynamics of autocatalytic reaction networks. IV: inhomogeneous replicator networks. Biosystems 26:1–19

    Article  CAS  PubMed  Google Scholar 

  • Steinmetz LM, Scharfe C, Deutschbauer AM, Mokranjac D, Herman ZS, Jones T, Chu AM, Giaever G, Prokisch H, Oefner PJ, Davis RW (2002) Systematic screen for human disease genes in yeast. Nat Genet 31:400–404

    CAS  PubMed  Google Scholar 

  • Terry MA (1992) Writing a multiple-choice test question. J Am Osteopath Assoc 92:112–114 123

    CAS  PubMed  Google Scholar 

  • Tong AH, Lesage G, Bader GD, Ding H, Xu H, Xin X, Young J, Berriz GF, Brost RL, Chang M, Chen Y, Cheng X, Chua G, Friesen H, Goldberg DS, Haynes J, Humphries C, He G, Hussein S, Ke L, Krogan N, Li Z, Levinson JN, Lu H, Menard P, Munyana C, Parsons AB, Ryan O, Tonikian R, Roberts T, Sdicu AM, Shapiro J, Sheikh B, Suter B, Wong SL, Zhang LV, Zhu H, Burd CG, Munro S, Sander C, Rine J, Greenblatt J, Peter M, Bretscher A, Bell G, Roth FP, Brown GW, Andrews B, Bussey H, Boone C (2004) Global mapping of the yeast genetic interaction network. Science 303:808–813

    Article  CAS  PubMed  Google Scholar 

  • Wachtershauser G (1990) Evolution of the first metabolic cycles. Proc Natl Acad Sci USA 87:200–204

    Article  CAS  PubMed  Google Scholar 

  • You L (2004) Toward computational systems biology. Cell Biochem Biophys 40:167–184

    Article  CAS  PubMed  Google Scholar 

  • Zotenko E, Mestre J, O’Leary DP, Przytycka TM (2008) Why do hubs in the yeast protein interaction network tend to be essential: reexamining the connection between the network topology and essentiality. PLoS Comput Biol 4:e1000140

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work is supported by the EU Specific Targeted Research Project consortium “Regulatory Control Networks Synthetic Lethality” (SYNLET, Grant 043312) and by the Crown Human Genome Center at the Weizmann Institute of Science. The authors wish to thank to Y. Pilpel, N. Barkai, and I. Tirosh for the useful discussions.

Author information

Authors and Affiliations

  1. Department of Molecular Genetics and the Crown Human Genome Center, Weizmann Institute of Science, Rehovot, 76100, Israel

    Aron Inger, Ariel Solomon, Barak Shenhav, Tsviya Olender & Doron Lancet

Authors
  1. Aron Inger
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ariel Solomon
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Barak Shenhav
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Tsviya Olender
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Doron Lancet
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Doron Lancet.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOC 229 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Inger, A., Solomon, A., Shenhav, B. et al. Mutations and Lethality in Simulated Prebiotic Networks. J Mol Evol 69, 568–578 (2009). https://doi.org/10.1007/s00239-009-9281-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00239-009-9281-y

Keywords

Search

Navigation