A Stochastic Model of Nonenzymatic Nucleic Acid Replication: “Elongators” Sequester Replicators

Abstract

Abstract. The origin of nucleic acid template replication is a major unsolved problem in science. A novel stochastic model of nucleic acid chemistry was developed to allow rapid prototyping of chemical experiments designed to discover sufficient conditions for template replication. Experiments using the model brought to attention a robust property of nucleic acid template populations, the tendency for elongation to outcompete replication. Externally imposed denaturation-renaturation cycles did not reverse this tendency. For example, it has been proposed that fast tidal cycling could establish a TCR (tidal chain reaction) analogous to a PCR (polymerase chain reaction) acting on nucleic acid polymers, allowing their self-replication. However, elongating side-reactions that would have been prevented by the polymerase in the PCR still occurred in the simulation of the TCR. The same finding was found with temperature and monomer cycles. We propose that if cycling reactors are to allow template replication, oligonucleotide phenotypes that are capable of favorably altering the flux ratio between replication and elongation, for example, by facilitating sequence-specific cleavage within templates, are necessary; accordingly the minimal replicase ribozyme may have possessed restriction functionality.

A Chemical Engineering Perspective on the Origins of Life

“…To copy a nucleic acid duplex, the duplex strands must be separated into single strands, each of which serves as a template for copying. However, even moderately short nucleic acid duplexes are quite stable owing to Watson Crick base pair stacking interactions [116,117], so that the result of copying is a template-copy duplex that is difficult to separate-a problem known as strand inhibition [118,119]. Many researchers have approached these problems by focusing on chemical modification of the modern nucleic acid structure.…”

On the Growth Rate of Non-Enzymatic Molecular Replicators

“…Spatially resolved template-directed replicators have been previously simulated in the Artificial Life community using two-dimensional cellular automata and continuous virtual physics [14,31,32]. The model we present here is conceptually similar to, but simpler than other coarse-grained DNA models, e.g., [33][34][35].…”

Adding to Hans Kuhn's thesis on the emergence of the genetic apparatus: Of the Darwinian advantage to be neither too soluble, nor too insoluble, neither too solid, nor completely liquid

“…The fact that the former were acids bearing acidic functionalities all along the chains makes them oligoanionic at pH values above ∼2 and therefore highly soluble in water at any length and molecular size. Despite the great autoreplicative potential of oligonucleotides and, as von Kiedrowski showed [30], their ability to grow populations at exponential rates when interacting with porous solids like silica, I see them not growing fast enough nor long enough [37], in order to adsorb efficiently in Hans Kuhn's mineral pores and clog them through the formation of aggregates. I see them growing perhaps to some very short length, being rapidly washed out of reach and disappear into the vast sea-an immense waste of energy.…”