Class I and II aminoacyl-tRNA synthetase tRNA groove discrimination created the first synthetase•tRNA cognate pairs and was therefore essential to the origin of genetic coding

Abstract

The genetic code likely arose when a bidirectional gene began to produce ancestral aminoacyl-tRNA synthetases (aaRS) capable of distinguishing between two distinct sets of amino acids. The synthetase Class division therefore necessarily implies a mechanism by which the two ancestral synthetases could also discriminate between two different kinds of tRNA substrates. We used regression methods to uncover the possible patterns of base sequences capable of such discrimination and find that they appear to be related to thermodynamic differences in the relative stabilities of a hairpin necessary for recognition of tRNA substrates by Class I aaRS. The thermodynamic differences appear to be exploited by secondary structural differences between models for the ancestral aaRS called synthetase Urzymes and reinforced by packing of aromatic amino acid side chains against the nonpolar face of the ribose of A76 if and only if the tRNA CCA sequence forms a hairpin. The patterns of bases 1, 2 and 73 and stabilization of the hairpin by structural complementarity with Class I, but not Class II aaRS Urzymes appears to be necessary and sufficient to have enabled the generation of the first two aaRS•tRNA cognate pairs, and the launch of a rudimentary binary genetic coding related recognizably to contemporary cognate pairs. As a consequence, it seems likely that non-random aminoacylation of tRNAs preceded the advent of the tRNA anticodon stem-loop. Consistent with this suggestion, coding rules in the acceptorstem bases also reveal a palimpsest of the codon•anticodon interaction, as previously proposed.

High-Resolution, Multidimensional Phylogenetic Metrics Identify Class I Aminoacyl-tRNA Synthetase Evolutionary Mosaicity and Inter-modular ‘Coupling

“…Descent of Class I and II aaRS from a single bidirectional ancestral gene [10, 14, 18, 19, 21, 32, 33] would underscore the likelihood that the aaRS of both families diverged, rather than converging to similar functions from different sources. Thus, the genetic coding table itself likely evolved by bifurcating pre-existing aaRS genes into specialized enzymes whose more discriminating specificities for tRNA and amino acid substrates enabled daughter synthetases to differentiate groups amino acids that previously had functioned as synonymous [46, 48, 58, 59]. It would be surprising if other branches of the proteome had not diverged from the ancestral aaRS, as suggested in Fig 6.…”