First arrived, first served: competition between codons for codon-amino acid stereochemical interactions determined early genetic code assignments.

Abstract

Stereochemical nucleotide-amino acid interactions, in the form of noncovalent nucleotide-amino acid interactions, potentially produced the genetic code's codon-amino acid assignments. Empirical estimates of single nucleotide-amino acid affinities on surfaces and in solution are used to test whether trinucleotide-amino acid affinities determined genetic code assignments pending the principle "first arrived, first served": presumed early amino acids have greater codon-amino acid affinities than ulterior ones. Here, these single nucleotide affinities are used to approximate all 64 × 20 trinucleotide-amino acid affinities. Analyses show that (1) on surfaces, genetic code codon-amino acid assignments tend to match high affinities for the amino acids that integrated earliest the genetic code (according to Wong's metabolic coevolution hypothesis between nucleotides and amino acids) and (2) in solution, the same principle holds for the anticodon-amino acid assignments. Affinity analyses match best genetic code assignments when assuming that trinucleotides competed for amino acids, rather than amino acids for trinucleotides. Codon-amino acid affinities stick better to genetic code assignments than anticodon-amino acid affinities. Presumably, two independent coding systems, on surfaces and in solution, converged, and formed the current translation system. Proto-translation on surfaces by direct codon-amino acid interactions without tRNA-like adaptors coadapted with a system emerging in solution by proto-tRNA anticodon-amino acid interactions. These systems assigned identical or similar cognates to codons on surfaces and to anticodons in solution. Results indicate that a prebiotic metabolism predated genetic code self-organization.