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Mol Biol Evol. 2019 Sep 3. pii: msz200. doi: 10.1093/molbev/msz200. [Epub ahead of print]

Can the RNA World still function without cytidine?

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Origins Institute and Dept of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario L8S 4L8, Canada.
Origins Institute and Dept of Physics and Astronomy, McMaster University, Hamilton, Ontario L8S 4M1, Canada.


Most scenarios for the origin of life assume that RNA played a key role in both catalysis and information storage. The A, U, G, and C nucleobases in modern RNA all participate in secondary structure formation and replication. However, the rapid deamination of C to U and the absence of C in meteorite samples suggest that prebiotic RNA may have been deficient in cytosine. Here we assess the ability of RNA sequences formed from a three-letter AUG alphabet to perform both structural and genetic roles in comparison to sequences formed from the AUGC alphabet. Despite forming less thermodynamically stable helices, the AUG alphabet can find a broad range of structures and thus appears sufficient for catalysis in the RNA world. However, in the AUG case, longer sequences are required to form structures with an equivalent complexity. Replication in the AUG alphabet requires GU pairing. Sequence fidelity in the AUG alphabet is low whenever G's are present in the sequence. We find that AUG sequences evolve to AU sequences if GU pairing is rare, and to RU sequences if GU pairing is common (R denotes A or G). It is not possible to conserve a G at a specific site in either case. These problems do not rule out the possibility of an RNA World based on AUG, but they show that it would be significantly more difficult than with a four-base alphabet.


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