An asymmetric underlying rule in the assignment of codons: Possible clue to a quick early evolution of the genetic code via successive binary choices

Abstract

Aminoacyl-tRNA synthetases (aaRSs) are responsible for creating the pool of correctly charged aminoacyl-tRNAs that are necessary for the translation of genetic information (mRNA) by the ribosome. Each aaRS belongs to either one of only two classes with two different mechanisms of aminoacylation, making use of either the 29OH (Class I) or the 39OH (Class II) of the terminal A76 of the tRNA and approaching the tRNA either from the minor groove (29OH) or the major groove (39OH). Here, an asymmetric pattern typical of differentiation is uncovered in the partition of the codon repertoire, as defined by the mechanism of aminoacylation of each corresponding tRNA. This pattern can be reproduced in a unique cascade of successive binary decisions that progressively reduces codon ambiguity. The deduced order of differentiation is manifestly driven by the reduction of translation errors. A simple rule can be defined, decoding each codon sequence in its binary class, thereby providing both the code and the key to decode it. Assuming that the partition into two mechanisms of tRNA aminoacylation is a relic that dates back to the invention of the genetic code in the RNA World, a model for the assignment of amino acids in the codon table can be derived. The model implies that the stop codon was always there, as the codon whose tRNA cannot be charged with any amino acid, and makes the prediction of an ultimate differentiation step, which is found to correspond to the codon assignment of the 22nd amino acid pyrrolysine in archaebacteria.

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

“…Key to this notion is that one branch of descent retains no coding information, and is therefore always available for punctuation, that is, the stop codons. Consistent with this differentiation model, the most recently discovered tRNA, which decodes the UAG codon as pyrrolysine in Archaea is the most ambiguous of all, interacting with both class I and class II lysyl tRNA synthetases (Delarue, 2007).…”

“…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).…”

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

“…Delarue [61] found an "asymmetric pattern" in the AGCU × CUGA layout of the codon table that depends on whether the encoded amino acid is recognized by a Class I aaRS or a Class II aaRS. 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. The two NRN columns are split into upper and lower 4A faces, in correspondence with a NYN ↔ NRN = Class I ↔ Class II anti-symmetry mirror of the 6A faces, etc., which leads to a binary partition of the codon set [61] and decision tree [14] much like our polytope splitting model (Section 6.5).…”

“…Polytope/graph faces with exact code symmetries contribute nil to the total edge weight; those with conservative symmetries less than those with near conservative or anti-symmetries. On the one hand symmetry breaking [21][22][23][24]65], code trees [14,61] and polytope splitting generate symmetric codes with error robustness, but on the other hand selection for codes with low error loads during the pre-LUCA evolution of early codes, the error minimization hypothesis [66], should generate codes with many symmetries.…”