UV photodamage pathways and the evolutionary selection of thymine over uracil in early genetic systems

The evolutionary selection of thymine over uracil in DNA presents a paradox from a photostability perspective, since thymine is found to be more susceptible to photodamage from the intense UV radiation present on the early Earth. This study addresses this paradox by providing a comparative spectroscopic analysis of thymine and uracil under controlled 265 nm UV irradiation. To that effect, we used steady-state absorption, fluorescence, and Raman spectroscopy to quantify and compare the photochemical behavior and damage kinetics of the two nucleobases. Our results show that thymine is inherently more photoreactive than uracil, exhibiting a faster overall rate of photodamage, a broader absorption band that increases spectral overlap with the primordial UVC spectrum, and a redshifted absorption maximum located in a spectral region where solar intensity was substantially higher. However, kinetic analysis of lesion pathways reveals that thymine forms irreversible (6-4) photoproducts at a significantly lower rate than uracil, instead directing UV-induced damage primarily toward the reversible cyclobutane pyrimidine dimer pathway. These findings support the hypothesis that canonical nucleobases were evolutionarily optimized not to minimize photodamage but to localize damage within the bases and direct lesion formation toward reversible pathways amenable to nonenzymatic self-repair.

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Publication Details

Journal
Proceedings of the National Academy of Sciences
Published
2026-08-03
DOI
https://doi.org/10.1073/pnas.2615278123
Primary Topic
DNA and Nucleic Acid Chemistry
Type
article
Field-Weighted Citation Impact
0.00

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article

UV photodamage pathways and the evolutionary selection of thymine over uracil in early genetic systems

Keyvan Khosh Abady, P. M. Rentzepis, Negar Karpourazar
Proceedings of the National Academy of Sciences
DNA and Nucleic Acid Chemistry
article

UV photodamage pathways and the evolutionary selection of thymine over uracil in early genetic systems

Keyvan Khosh Abady, P. M. Rentzepis, Negar Karpourazar
article en

Abstract

The evolutionary selection of thymine over uracil in DNA presents a paradox from a photostability perspective, since thymine is found to be more susceptible to photodamage from the intense UV radiation present on the early Earth. This study addresses this paradox by providing a comparative spectroscopic analysis of thymine and uracil under controlled 265 nm UV irradiation. To that effect, we used steady-state absorption, fluorescence, and Raman spectroscopy to quantify and compare the photochemical behavior and damage kinetics of the two nucleobases. Our results show that thymine is inherently more photoreactive than uracil, exhibiting a faster overall rate of photodamage, a broader absorption band that increases spectral overlap with the primordial UVC spectrum, and a redshifted absorption maximum located in a spectral region where solar intensity was substantially higher. However, kinetic analysis of lesion pathways reveals that thymine forms irreversible (6-4) photoproducts at a significantly lower rate than uracil, instead directing UV-induced damage primarily toward the reversible cyclobutane pyrimidine dimer pathway. These findings support the hypothesis that canonical nucleobases were evolutionarily optimized not to minimize photodamage but to localize damage within the bases and direct lesion formation toward reversible pathways amenable to nonenzymatic self-repair.

Proceedings of the National Academy of SciencesVol. 123(33)
Texas A&M University (US)
Air Force Office of Scientific Research
Openalex Percentile: Top 15%
DNA and Nucleic Acid Chemistry
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