Nonequilibrium replication and selection from reactive nucleotides using hyperexponential RNA polymerization in a thermal trap

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Can we use the disequilibrium setting of a thermal gradient to generate a replication-selection process, based only on reactive nucleotides such as cGMP and cCMP? We have recently established an experimental platform that promises to make this ambitious goal attainable. In particular, we have already demonstrated crucial properties required to kickstart a spontaneous process that mimics the transition from a chemical to a biological world, which must have occurred during the Origin of Life. A central issue is the question of how to create such a process while starting from prebiotically plausible conditions, i.e. low concentrations of simple building blocks and in the absence of protein enzymes. We have found that thermal trapping (convection and thermophoresis in a cleft) can be a natural solution to this problem, which in essence uses a global physical non-equilibrium to strongly accumulate molecules and to drive chemical reactions. For instance, we demonstrated recently [C.B. Mast, S. Schink, U. Gerland and D. Braun, PNAS 110, 8030-8035 (2013)], using double-stranded DNA blocks, that a thermal trap can lead to a hyperexponential enhancement of polymerization. We now strive to take this to the single-nucleotide level, exploiting the recently shown fast polymerization of 20mers of RNA from cGMP found by the di Mauro group, which we already confirmed in our lab, albeit in dry conditions. This reaction perfectly matches the conditions for strong thermal trapping and promises a rich structure of replication and selection under the simple non-equilibrium setting of a thermal gradient. We will pursue three major goals:1. Hyperexponential Polymerization. Creation of long RNA molecules in a Thermal Trap. The polymers will be created from a steady inflow of cGMP molecules at low concentrations.2. Codon-Replicator based on tRNA. Replicate long codon sequences using hairpin ligation of cGMP. Starting from poly-C templates, replication will be enhanced by convection and trapping.3. Theoretical description and exploration of the interplay between the non-equilibrium physics of the thermal trap and the stochastic chemical reactions. The approaches will range from simplified analytical treatments to full finite element simulations of detailed models. All approaches are tightly integrated with the experiments.