Theoretical minimal RNA rings recapitulate the order of the genetic code's codon-amino acid assignments

Abstract

BackgroundTheoretical minimal RNA rings form stem-loop hairpins coding for each of the 20 amino acids and a stop, presumably mimicking life's first minimal coding and self-replicating RNAs. They resemble consensual tRNAs. Mean amino acid positions in proteins follow the genetic code's consensual amino acid inclusion order, a 5′-late-to-3′-early amino acid gradient. HypothesisWe translated minimal RNA rings to test whether translated peptides share that gradient with modern proteins, using a) ribosomal translation, non-overlapping consecutive codons; and b) frameless translation advancing nucleotide by nucleotide, producing partially overlapping codons. ResultsFor frameless translation, most RNA rings code for a 5′-late-to-3′early amino acid gradient. Gradients indicate decreasing amino acid metabolic costs, from large to small amino acids. For ribosomal translation, the 5′-late-to-3′early amino acid gradient evolves from early to late RNA rings when ranked according to yields in Miller's experiment of their predicted anticodon's cognate amino acid. ConclusionsSimulations that produced in silico minimal RNA rings didn't account for coded amino acid properties. Yet, produced peptides remind actual proteins, and suggest ancestral frameless translation of partially overlapping trinucleotides advancing by single nucleotide steps, constrained by resource scarcity. Minimal RNA rings reflect the transition from frameless to ribosomal translation and are realistic candidates for ancestral tRNAs.