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

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 synergistically 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.

Functional Assemblies Emerging in Complex Mixtures of Peptides and Nucleic Acid-Peptide Chimeras.

Striking synergy between nucleic acids and proteins is exhibited in living cells. Whether such mutual activity can be performed using simple supramolecular nucleic acid-peptide (NA-pep) architectures remains a mystery. To shed light on this question, we studied the emergence of a primitive synergy in assemblies of short DNA-peptide chimeras. Specifically, we characterized multiple structures forming along gradual mixing trajectory, in which a peptide solution was seeded with increasing amounts of NA-pep chimeras. We report on the systematic change from ß-sheet-peptide-based fibrillar architectures into the spherical structures formed by the conjugates. Remarkably, we find that through forming onion-like structures, the conjugates exhibit increased DNA hybridization stability and bind small molecules more efficiently than the peptides or DNA alone. A brief discussion highlights the implications of our findings for the production of new materials and for research on the origin of life.