Abstract
The modern genetic code reveals numerous traces of specific relationships between the early codons which, together with its internal asymmetries, suggest a sequential appearance of the nucleobases in primitive RNA molecules. Keeping the hypothesis of triplet pairings between primitive RNA molecules at the origin of the code, this work systematically examines complete codon-anticodon interaction matrices assuming distinct pairing options at each position of the triplet duplexes. Application of these principles suggests that a 27-codon precursor having a reasonable coding capacity for short peptide synthesis could have started with primitive RNA molecules able to form two distinct pairs with different free energies between a single purine and two pyrimidines (such as G with C and U). Conservation of the same pairing options at positions 1 and 2 of codons at the arrival of a second purine with distinct pairing preferences (such as A) generated a 64-codon intermediate code made of interrelated pairs or groups of codons (designated here as intricacy). The numerous traces of this hypothetical scheme that are visible in the standard and variant forms of the modern code demonstrate without ambiguity that the ancestral codon-anticodon duplexes required high energetic pairings at their central position (Watson-Crick) but tolerated less energetic pairings at the first codon position (G • U type). Combined with the sequential appearance of the nucleobases, the predicted codon intricacy allows a stepwise reconstruction of the evolution of the coding repertoire, by simple a posteriori comparison to the modern code. This reconstruction reveals a remarkable internal coherence in terms of amino acids and tRNA synthetases recruitment. The code started with a group of amino acids (Ala, Gly, Pro, Ser and Thr) that are now all activated by class II tRNA synthetases before reaching an intermediate period during which up to 14 distinct amino acids could be encoded by a full set of intricated codons. The perfect coincidence between the last 6 amino acids predicted in this reconstruction and the speculated action of the arrival of free atmospheric oxygen on proteins is spectacular, and suggests that the code has only reached its present form after the great oxidation event.
Highlights
More than half a century after the elucidation of the codon table [1], the origin of the genetic code remains the most fascinating question of all biological processes in which products are needed to synthesize the elements of their own synthesis
The code started with a group of amino acids (Ala, Gly, Pro, Ser and Thr) that are all activated by class II tRNA synthetases before reaching an intermediate period during which up to 14 distinct amino acids could be encoded by a full set of intricated codons
During more than five decades, the genetic code has been contemplated in multiple manners, in search of its logic and possible origin
Summary
More than half a century after the elucidation of the codon table [1], the origin of the genetic code remains the most fascinating question of all biological processes in which products are needed to synthesize the elements of their own synthesis. Conservation of the same pairing options during expansion of the precursor code at the arrival of A (or precursor) produced a fully-coding hypothetical intermediate in which defined codons were interconnected to one another in a defined network due to their common interactions with some anticodons Traces of this phenomenon, referred to here as codon intricacy (to distinguish from coding degeneracy) are visible into the standard and variant forms of the modern code. Keeping the hypothesis that unsplit codon families in the modern code are more representative of its ancestral form than the split ones [39], this asymmetry favors the idea of a 27-codon precursor code built on primitive RNA molecules composed of G, C and U only. Further deconstruction of the modern genetic code assuming even more primitive RNA molecules made of only two nucleobases gives no more conclusive results, except that G and C could have been the earliest nucleobases as already proposed [39, 49,50,51]
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