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 replicating as a quasi‐species 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 appear 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 nonrandom aminoacylation of tRNAs preceded the advent of the tRNA anticodon stem‐loop. Consistent with this suggestion, coding rules in the acceptor‐stem bases also reveal a palimpsest of the codon–anticodon interaction, as previously proposed. © 2019 IUBMB Life, 2019 © 2019 IUBMB Life, 71(8):1088–1098, 2019

Aminoacyl-tRNA synthetases

“…This extremely reduced version of an aaRS has been termed an urzyme (´ur´ meaning primitive, original, earliest) and usually comprises the amino acid activation and acyl-transfer active sites of the full-length enzyme. Despite containing only slightly more than a hundred amino acids, urzymes still retain the basic catalytic capabilities of the synthetase (Augustine and Francklyn 1997;Pham et al 2010;Carter 2017;Carter and Wills 2019). For example, a 130 amino acid long tryptophanyl-tRNA synthetase urzyme has been shown to accelerate Trp activation 109-fold (compared to the spontaneously activation rate) (Pham et al 2007) and similar results have been achieved with HisRS (Li et al 2011).…”

Impedance Matching and the Choice Between Alternative Pathways for the Origin of Genetic Coding

“…There is overwhelming evidence that the two modern aaRS superfamilies descended from small (M W ~14 KD) Class I and II Urzyme-like proteins encoded by the +/− strands of a single gene [ 8 , 43 , 46 , 47 , 48 ]. Secondary structures of these two putative aaRS ancestors enabled them to discriminate between large (Class I) and small (Class II) amino acid side chains ( Figure 4 A; [ 4 ]), and between the reverse hairpin (Class I) and extended helical path (Class II) of the 3′-terminal DCCA extensions of available tRNA-like mini-helices [ 49 , 50 ]. These properties fulfill requirements for operating a binary (n = 2) code able to distinguish two subsets of the available amino acids as a minimal implementation of translation coupled to replication.…”

Reciprocally-coupled Gating: Strange Loops in Bioenergetics, Genetics, and Catalysis

“…(ii) The Class partitioning of amino acid substrates by contemporary aaRS appears to be according to their side-chain volume [8][9][10]. (iii) Class-dependent discrimination between cognate and non-cognate tRNA [81,82] and amino acid [83] substrates has been attributed to secondary structural differences between the two aaRS Classes, and does not appear to depend on specific side chains. One can thus readily imagine quite deeply-based ancestry of the rudimentary distinctions necessary for the initial differentiation between coding letters.…”