Viscous solvents as an environment for nucleic acid replication
He, Christine Yi
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Many hypotheses concerning the nature of early life assume that genetic information was once transferred through the template-directed synthesis of RNA, prior to the evolution of genetically encoded protein synthesis. However, despite more than half a century of research into the chemical origins of nucleic acids, a robust route to the abiotic synthesis of nucleic acid polymers is unclear. In particular, identifying the earliest mechanism for enzyme-free replication of nucleic acids remains an elusive goal. A biophysical problem known as strand inhibition limits copying of a nucleic acid duplex: transferring information from a template sequence in the presence of its complementary strand is inhibited by the stability of the template duplex. Strand inhibition is a major bottleneck in understanding how sustained RNA replication evolved on the early Earth. In this thesis, I describe a robust, prebiotically plausible route to enzyme-free replication of nucleic acids, driven by hot/cool cycles in viscous environments. Viscous solvents enable kinetic trapping of a nucleic acid duplex as single strands, providing a time window for the assembly and ligation of oligonucleotide substrates on the single stranded templates. I have shown that viscous solvents can be utilized to overcome strand inhibition, enabling copying of a gene-length template duplex (>300 nt), a process which is highly unfavorable in aqueous conditions. Additionally, viscosity enables copying of an RNA duplex containing a hammerhead ribozyme motif, suggesting a potential route for the selection and amplification of catalytically active RNA on the prebiotic Earth.