Departure from Randomness: Evolution of Self-Replicators that can Self-Sort through Steric Zipper Formation

Darwinian evolution of synthetic self-replicating entities is likely to have an important role in the emergence of life from inanimate chemical matter. Darwinian evolution of self-replicators requires that these (i) have structural space accessible to them; (ii) occupy only part of this space at any one time, and (iii) navigate this space through a process of mutation and selection. We now report a system of self-replicating hexameric macrocycles that emerges upon mixing two building blocks. It occupies a subset of possible building block sequences. Specific interactions between the building blocks, most likely through steric zipper formation involving the interdigitation of a phenylalanine residue of one building block between two leucine residues of the other building block, results in the preferential formation of a hexamer with a sequence in which the two building blocks alternate. When this system was exposed to two different replication-destruction regimes, different replicator mutant distributions were selected for. When the destruction process was non-selective (mediated by outflow in an open system) the fastest replicating sequences dominated, overriding the preference for zipper formation observed in a closed vial. However, when destruction was mediated chemically (and therefore potentially selective) the replicator mutant that combined adequate resistance to reduction with adequate replication speed and was capable of steric zipper formation, became dominant. These results constitute a rudimentary form of Darwinian evolution where replicators adapt to a changing selection pressure through mutation and selection.