Codon Directional Asymmetry Suggests Swapped Prebiotic 1st and 2nd Codon Positions

Abstract

Background: Codon directional asymmetry (CDA) classifies the 64 codons into palindromes (XYX, CDA = 0), and 5′- and 3′-dominant (YXX and XXY, CDA < 0 and CDA > 0, respectively). Previously, CDA was defined by the purine/pyrimidine divide (A,G/C,T), where X is either a purine or a pyrimidine. For the remaining codons with undefined CDA, CDA was defined by the 5′ or 3′ nucleotide complementary to Y. This CDA correlates with cognate amino acid tRNA synthetase classes, antiparallel beta sheet conformation index and the evolutionary order defined by the self-referential genetic code evolution model (CDA < 0: class I, high beta sheet index, late genetic code inclusion). Methods: We explore associations of CDAs defined by nucleotide classifications according to complementarity strengths (A:T, weak; C:G, strong) and keto-enol/amino-imino groupings (G,T/A,C), also after swapping 1st and 2nd codon positions with amino acid physicochemical and structural properties. Results: Here, analyses show that for the eight codons whose purine/pyrimidine-based CDA requires using the rule of complementarity with the midposition, using weak interactions to define CDA instead of complementarity increases associations with tRNA synthetase classes, antiparallel beta sheet index and genetic code evolutionary order. CDA defined by keto-enol/amino-imino groups, 1st and 2nd codon positions swapped, correlates with amino acid parallel beta sheet formation indices and Doolittle’s hydropathicities. Conclusions: Results suggest (a) prebiotic swaps from N2N1N3 to N1N2N3 codon structures, (b) that tRNA-mediated translation replaced direct codon-amino acid interactions, and (c) links between codon structures and cognate amino acid properties.

The primordial tRNA acceptor stem code from theoretical minimal RNA ring clusters

“…4. This consists of processes that produced the RNA rings, from the presumably stereochemical determination of codon-amino acid assignments [67], and biases for short pentamers with nonredundant coding across frames [68] which could have accreted into RNA rings. The aim is to understand what makes RNA rings such useful, and perhaps efficient, simulators of prebiotic evolution, independently of the possibility that RNA rings are the actual primordial sequences.…”

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

“…Hence because RNA rings resemble proto-tRNAs, the genetic code had to exist before tRNAs and proto-tRNAs. The association of codon affinity with hydrophobicity for RNA rings indicates that translation according to the genetic code preexisted tRNA-mediated translation, potentially along a different codon structure where nucleotides at 1st and 2nd codon positions were switched [110,111], but also evolved towards the situation observed in modern genes during the evolution of this RNA ringbased primordial RNA system [112][113][114]. Theoretical minimal RNA rings are realistic models for the RNA world during the transition from translation based on codon affinity for amino acids and lacking tRNA-like adaptors to tRNA-like mediated translation.…”

Negative CG dinucleotide bias: An explanation based on feedback loops between Arginine codon assignments and theoretical minimal RNA rings

“…Sequences belonging to these 25 RNA rings occur within ancient conserved genes. [ 90 ] Their codon usage is biased towards codons with symmetry‐breaking patterns [ 91–93 ] corresponding to codons coding for amino acids that are cognates of class II tRNA synthetases, [ 94 ] the presumed ancestral tRNA synthetase class. [ 95,96 ] Codon usages also produce complementarity correlations between codons and coded amino acids, [ 97 ] as known from natural mRNAs and coded peptides.…”