RNA Rings Strengthen Hairpin Accretion Hypotheses for tRNA Evolution: A Reply to Commentaries by Z.F. Burton and M. Di Giulio.

Theoretical minimal RNA ring design ensures coding over the shortest length once for each coding signal (start and stop codons, and each amino acid) and their hairpin configuration. These constraints define 25 RNA rings which surprisingly resemble ancestral tRNA loops, suggesting commonalities between RNA ring design and proto-tRNAs. RNA rings share several other properties with tRNAs, suggesting that primordial RNAs were multifunctional peptide coding sequences and structural RNAs. Two hypotheses, respectively, by M. Di Giulio and Z.F. Burton, derived from cloverleaf structural symmetries suggest that two and three, respectively, stem-loop hairpins agglutinated into tRNAs. Their authors commented that their respective structure-based hypotheses reflect better tRNA structure than RNA rings. Unlike these hypotheses, RNA ring design uses no tRNA-derived information, rendering model predictive power comparisons senseless. Some analyses of RNA ring primary and secondary structures stress RNA ring splicing in their predicted anticodon's midst, indicating ancestrality of split tRNAs, as the two-piece model predicts. Advancement of knowledge, rather than of specific hypotheses, gains foremost by examining independent hypotheses for commonalities, and only secondarily for discordances. RNA rings mimick ancestral biomolecules including tRNAs, and their evolution, and constitute an interesting synthetic system for early prebiotic evolution tests/simulations.