Self-replication of chemical systems based on recognition within a double or a triple helix: a realistic hypothesis

A scenario is proposed by which non-enzymatic self-replication of short RNA molecules could occur. The hypothesis is illustrated for the self-replication of an oligopyrimidine (Y) strand. The successful replication of Y requires a series of plausible steps. The first, experimentally feasible, step involves the template-directed polynucleotide synthesis, based on Watson-Crick base pairing, of an oligopurine (R) strand using Y as the template, and chemically activated mononucleotides as the building blocks. This step will result in the formation of an oligopyrimidine.oligopurine (YR) double helix. The second step requires the use of the double helix as the template for the synthesis of a second oligopyrimidine (Y') strand from activated pyrimidine monomers. This synthesis could be facilitated by the binding of the monopyrimidines in the major groove of the YR double helix, via Hoogsteen-type base pairing with the R strand, establishing in that sense triple helix recognition. This step, if successful, should result in the formation of a new strand, Y', that runs parallel to the oligopurine strand. Y' differs from Y in that all 3'-5' phosphodiester linkages in Y are replaced by 5'-3' linkages in Y'. The resulting triple helix (YRY') is in dynamic equilibrium with YR and free Y'. In subsequent steps, unassociated Y' directs the synthesis of the complementary oligopurine (R') strand forming a new double helix Y'R' that may direct the synthesis of an oligopyrimidine strand, Y, that is expected to be identical to the first strand that started the whole sequence. An attempt is made to generalize the above hypothesis to mixed oligonucleotides containing all four bases and identify the limitations of this hypothesis.