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J Theor Biol. 2018 Jun 7;446:128-136. doi: 10.1016/j.jtbi.2018.03.012. Epub 2018 Mar 12.

Evolutionary advantage of directional symmetry breaking in self-replicating polymers.

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Integrated Mathematical Oncology Department,Tampa, FL, USA. Electronic address:
Integrated Mathematical Oncology Department,Tampa, FL, USA; Cancer Biology and Evolution Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA. Electronic address:


Due to the asymmetric nature of the nucleotides, the extant informational biomolecule, DNA, is constrained to replicate unidirectionally on a template. As a product of molecular evolution that sought to maximize replicative potential, DNA's unidirectional replication poses a mystery since symmetric bidirectional self-replicators obviously would replicate faster than unidirectional self-replicators and hence would have been evolutionarily more successful. Here we carefully examine the physico-chemical requirements for evolutionarily successful primordial self-replicators and theoretically show that at low monomer concentrations that possibly prevailed in the primordial oceans, asymmetric unidirectional self-replicators would have an evolutionary advantage over bidirectional self-replicators. The competing requirements of low and high kinetic barriers for formation and long lifetime of inter-strand bonds respectively are simultaneously satisfied through asymmetric kinetic influence of inter-strand bonds, resulting in evolutionarily successful unidirectional self-replicators. Within our model, circular strands, the configuration prefered by primitive life forms, have higher replicative potential compared to linear strands.


3’-5’ unidirectional replication; Asymmetric cooperativity; DNA strand directionality; Primordial heteropolymers

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