Theoretical minimal RNA rings mimick molecular evolution before tRNA-mediated translation: codon-amino acid affinities increase from early to late RNA rings

Abstract

Nucleotide affinities for noncovalent interactions with amino acids produce associations between mRNAs and cognate peptides, potentially regulating ribosomal translation. Correlations between nucleotide affinities and residue hydrophobicity are explored for 25 theoretical minimal RNA rings, 22 nucleotide-long RNAs designed in silico to code for each amino acid once after three translation rounds, and forming stem-loop hairpins. This design presumably mimicks life’s first RNAs. RNA rings resemble consensual tRNAs, suggesting proto-tRNA function, predicted anticodon and cognate amino acid. The 25 RNA rings and their presumed evolutionary order, deduced from the genetic code integration order of the amino acid cognate to their predicted anticodon, produces noteworthy associations with several ancient properties of the cell’s translational machinery. Here we use this system to explore the evolution of codon affinity-residue hydrophobicity correlations, assuming these reflect pre-tRNA and pre-ribosomal translations. This hypothesis expects that correlations decrease with genetic code inclusion orders of RNA ring cognates. RNA ring associations between nucleotide affinities and residue hydrophobicities resemble those from modern natural genes/proteins. Association strengths decrease with genetic code inclusion ranks of proto-tRNA cognate amino acids. In silico design of minimal RNA rings didn’t account for affinities between RNA and peptides coded by these RNAs. Yet, interactions between RNA rings and translated cognate peptides resemble modern natural genes. This property is strongest for ancient RNA rings, weakest for recent RNA rings, spanning a period during which modern tRNA- and ribosome-based translation presumably evolved. Results indicate that translation lacking tRNA-like adaptors based on codon-amino acid affinities and the genetic code pre-existed tRNA-mediated translation. Theoretical minimal RNA rings appear valid prebiotic peptide-RNA world models for the transition between pre-tRNA- and tRNA-mediated translations.