On the origin of the genetic code: signatures of its primordial complementarity in tRNAs and aminoacyl-tRNA synthetases

Abstract

If the table of the genetic code is rearranged to put complementary codons face-to-face, it becomes apparent that the code displays latent mirror symmetry with respect to two sterically different modes of tRNA recognition. These modes involve distinct classes of aminoacyl-tRNA synthetases (aaRSs I and II) with recognition from the minor or major groove sides of the acceptor stem, respectively. We analyze the anticodon pairs complementary to the face-toface codon couplets. Taking into account the invariant nucleotides on either side (5 0 and 3 0 ), we consider the risk of anticodon confusion and subsequent erroneous aminoacylation in the ancestral coding system. This logic leads to the conclusion that ribozymic precursors of tRNA synthetases had the same two complementary modes of tRNA aminoacylation. This surprising case of molecular mimicry (1) shows a key potential selective advantage arising from the partitioning of aaRSs into two classes, (2) is consistent with the hypothesis that the two aaRS classes were originally encoded by the complementary strands of the same primordial gene and (3) provides a 'missing link' between the classic genetic code, embodied in the anticodon, and the second, or RNA operational, code that is embodied mostly in the acceptor stem and is directly responsible for proper tRNA aminoacylation.

The Graph, Geometry and Symmetries of the Genetic Code with Hamming Metric

“…Rodin and Rodin [62] rearrange the table differently with "complementary" codons "face to face" to show a "latent mirror symmetry," while Jestin and Soulé [50] describe this pattern by six "base substitution symmetries". The pattern maps to distinct polytope faces and "recapitulates" the progression of splits of our evolution model: the two NUN and NCN 6A faces (table columns) are Class I and Class II respectively, in correspondence with a NUN ↔ NCN = Class I ↔ Class II anti-symmetry mirror in our nomenclature.…”

An alternative to the RNA World Hypothesis

“…65 These problems have been addressed by numerous hypotheses, 66,67 some of which have accepted the notion that the genetic code originated in an RNA world, perhaps to assist ribozyme activity. 68,69 The idea that the full genetic code evolved from a subset of codons coding for a subset of amino acids began with the proposal that an RRY mRNA (R=purine, Y=pyrimidine) could only be read in one frame. 70 Eigen and Winkler-Oswatitsch proposed that the universal code evolved from one in which glycine, alanine, valine, and aspartic acid were coded by GNY codons (N=any base), with the central base determining which one of the four amino acids was incorporated into a growing polypeptide chain.…”

“…7 In subsequent proposals the GNY code has been refined to a GNC set of codons that would bind to complementary GNC anticodons, allowing two pairs of G-C triple hydrogen bonds to stabilize codon-anticodon binding. 69,[72][73][74] This set of codons would enable opposite strands of RNA to each code for proteins. [75][76][77] The strengths of codon-anticodon interactions vary, with important contributions coming from G-C triple hydrogen bonds and stabilization of G-C base pairs by A-minor interactions.…”

Whence the genetic code?: Thawing the ‘Frozen Accident’

“…Two successive purines or pyrimidines are unlikely to be confused with their complements. Alternating purine/pyrimidine dinucleotides in the anticodon are quite likely to be confused, as indicated by the yellow dashed lines (adapted from Rodin and Rodin, 2008;Figures 3 and 4 and Table 3). …”

“…In this issue of Heredity, Rodin and Rodin (2008) seek a unified molecular interpretation of the genetic code based largely on two recent papers that propose to fill these gaps (Rodin and Rodin, 2006a, b;Delarue, 2007).…”