Primitive selection of the fittest emerging through functional synergy in nucleopeptide networks

Anil Kumar Bandela, Nathaniel Wagner, Hava Sadihov, Sara Morales-Reina, Agata Chotera-Ouda, Kingshuk Basu, Rivka Cohen-Luria, Andrés de la Escosura, Gonen Ashkenasy

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


Many fundamental cellular and viral functions, including replication and translation, involve complex ensembles hosting synergistic activity between nucleic acids and proteins/peptides. There is ample evidence indicating that the chemical precursors of both nucleic acids and peptides could be efficiently formed in the prebiotic environment. Yet, studies on nonenzymatic replication, a central mechanism driving early chemical evolution, have focused largely on the activity of each class of these molecules separately. We show here that short nucleopeptide chimeras can replicate through autocatalytic and cross-catalytic processes, governed syn-ergistically by the hybridization of the nucleobase motifs and the assembly propensity of the peptide segments. Unequal assembly-dependent replication induces clear selectivity toward the formation of a certain species within small networks of complementary nucleopeptides. The selectivity pattern may be influenced and indeed maximized to the point of almost extinction of the weakest replicator when the system is studied far from equilibrium and manipulated through changes in the physical (flow) and chemical (template and inhibition) conditions. We postulate that similar processes may have led to the emergence of the first functional nucleic-acid-peptide assemblies prior to the origin of life. Furthermore, spontaneous formation of related replicating complexes could potentially mark the initiation point for information transfer and rapid progression in complexity within primitive environments, which would have facilitated the development of a variety of functions found in extant biological assemblies.

Original languageEnglish
Article numbere2015285118
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number9
StatePublished - 2 Mar 2021


  • Chemical evolution
  • Molecular networks
  • Nucleic-acid-peptide conjugates
  • Self-replication

ASJC Scopus subject areas

  • General


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