Journal of Molecular Evolution

, Volume 69, Issue 5, pp 568–578 | Cite as

Mutations and Lethality in Simulated Prebiotic Networks

  • Aron Inger
  • Ariel Solomon
  • Barak Shenhav
  • Tsviya Olender
  • Doron LancetEmail author


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.


Origin of life Mutations Networks Lethality Synthetic lethality 



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.

Supplementary material

239_2009_9281_MOESM1_ESM.doc (230 kb)
Supplementary material 1 (DOC 229 kb)


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Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Aron Inger
    • 1
  • Ariel Solomon
    • 1
  • Barak Shenhav
    • 1
  • Tsviya Olender
    • 1
  • Doron Lancet
    • 1
    Email author
  1. 1.Department of Molecular Genetics and the Crown Human Genome CenterWeizmann Institute of ScienceRehovotIsrael

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