Illuminating the Path to Evolution: UV-Induced Repair as a Precursor to Biological Function

Abstract

The origin of life was a planetary process that required both the synthesis of biomolecules and environmental conditions in which those molecules could persist and function. Among the most significant of these conditions was ultraviolet (UV) irradiation from the Sun, which likely drove prebiotic synthesis, yet caused photodamage. This dissertation investigates how UV light may have acted not only as a destructive force, but also as a protective and selective one, by promoting nonenzymatic repair of cyclobutane pyrimidine dimers (CPDs), the most common UV-induced lesions in nucleic acids. In doing so, this dissertation advances a framework in which molecular survival, photochemical resilience, and environmental coupling were central to the transition from prebiotic chemistry to early biological function. In Chapter 1, I establish the geological and chemical context for life’s emergence, with particular emphasis on UV-rich surface environments, prebiotic feedstock accumulation, and the role of environmental selection in shaping the earliest biomolecular systems. In Chapter 2, I present experimental methods for generating and quantifying CPD damage and repair in short nucleic acid oligomers in a laboratory setting, using UV/Vis spectroscopy and HPLC. Using these methods, I demonstrate for the first time that RNA can undergo intrinsic UV-induced self-repair. In the RNA sequence GAU=U, repair to GAUU occurs through charge transfer from an adjacent GA motif, with a quantum yield of 0.23% and a maximum recovery of approximately 16% under prolonged irradiation. Comparative ultrafast spectroscopy shows that the intermediate charge-transfer states in RNA and DNA are similarly long-lived, supporting a photolyase-like but enzyme-free repair mechanism. These results indicate that intrinsic self-repair could have contributed to the photostability and selection of early RNA sequences on the prebiotic Earth. I next show in Chapter 4 that chimeric nucleic acids can display even greater intrinsic photochemical resilience. In the sequence d(GAU=U), self-repair proceeds with a quantum yield of 1.16%, exceeding both previously measured self-repair yields in canonical RNA and DNA and the corresponding damage yield in d(UU). This system is, to my knowledge, the first oligonucleotide in which intrinsic repair outcompetes CPD damage formation under continuous UV irradiation. These findings reveal that backbone conformation and pyrimidine identity strongly influence repair efficiency and suggest that chimeric sequences may have represented especially UV-resistant precursors to canonical DNA. In Chapter 5, I demonstrate a distinct geochemical route to nonenzymatic repair through ferrocyanide-mediated generation of solvated electrons. Under 285 nm irradiation, ferrocyanide promotes repair in both DNA and RNA, with measured quantum yields of approximately 0.90% for d(T=T) and 0.5% for U=U at prebiotically plausible ferrocyanide concentrations. Repair efficiency increases strongly with lesion concentration, reaching 2.26% at [d(T=T)] = 198 µM, consistent with a concentration-dependent propagation-associated contribution. This result broadens the known space of abiotic repair mechanisms beyond sequence-intrinsic self-repair and shows that simple environmental redox chemistry could recapitulate a core function later performed by enzymes. More broadly, these results suggest that nucleic acid survival may have depended on local redox landscapes, in which ferrocyanide and other UV-active environmental reductants supplied reducing power for repair. Taken together, these studies support a view of the early Earth as a photochemical selection environment in which UV light, nucleic acid structure, and geochemical context jointly shaped which molecules endured. In this framework, repair is not merely protection from damage, but a mechanism for persistence, accumulation, and the emergence of environmentally responsive function. More broadly, this work links prebiotic chemistry to the later evolution of biological regulation and suggests that the earliest informational polymers may have been selected not only for their ability to form, but for their ability to survive and respond to their environment.