Physical organic principles governing the spontaneous prebiotic emergence of proto-nucleic acids

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Fialho, David M.
Hud, Nicholas V.
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The origin of life on Earth is a poorly understood phenomenon. The influential RNA world hypothesis states that, at some early stage in the evolution of life, RNA was the sole (or primary) biopolymer, performing both informational and catalytic functions. In some interpretations of the RNA world hypothesis, RNA is the first polymer to arise from prebiotic chemical processes. However, the prebiotic synthesis of RNA is problematic: forming the various components of RNA selectively and covalently linking them is prebiotically difficult. For these reasons, it has been hypothesized that RNA is the product of evolution. In this view of the origin of nucleic acids, RNA is the penultimate member in an evolutionary series of nucleic acids, starting with the first informational polymer to arise on the early Earth: the proto-nucleic acid. The chemical components of the proto-nucleic acid, and of pre-RNAs, are not necessarily the same as those in RNA, but their functions were similar. In this dissertation, candidate proto-nucleic acid components, such as noncanonical nucleobases and noncanonical backbone motifs, are described, and criteria to judge their candidacy, such as chemical reactivity and propensity for oligomerization and self-assembly in water, are discussed. Although the chemical space of informational polymers is vast, the principles arrived at greatly reduce the size of this space by ruling out inviable chemical motifs. This work culminates with the introduction of a new class of informational polymer that is considered a strong candidate for proto-RNA. Important general principles for the evolution of proto-nucleic acids and pre-RNAs are also discussed.
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