Evolution of the genetic code from the GC- to the AGUC-alphabet

A hypothesis of the evolution of the genetic code is proposed, the leading mechanism of which is the nucleotide spontaneous damage leading to AT-enrichment of the genome. The hypothesis accounts for stability of the genetic code towards point mutations, the presence of code dialects, and the symmetry of the genetic code table. To account for the extant structure of the genetic code (all dialects), I can propose the hypothesis of the evolution of the current four-letter alphabet from an earlier, two-letter one. In this hypothesis, deamination of cytosine plays the key role. Remembering that DNA and cytosine methylation seem to be of quite recent origin, it would be correct to write C→U. Cytosine deamination obviously causes just partial loss of complementarity. There can be two hydrogen bonds between guanine and uracil, at first glance making this pair similar to the adenine-thymine (uracil) pair. The possibility of the formation of the complementary pair is illustrated by coupling of these nucleotides at the third position of the codon and anticodon (Table 1). anticodon codon C G G C, U U G, A A U Table 1. Ambiguity of nucleotide coupling at the third position of the codon and anticodon [4]. Based on the assumption that the two most complex nucleotides, guanine and thymine, were before uracil and adenine, one can reconstruct the stages of the genetic code evolution. Table 1 clearly illustrates that if there were just two letters (C, G), the possibility of the formation of the G=U pair facilitated the process of incorporating the new letter into the code, and in the next stage, the possibility of the formation of the U=A pair facilitated the emergence of adenine. Formally speaking, a reverse order of the emergence of these letters is also possible – first, (A, U), then, G and, last, C. The realization of this order, however, is physically ungrounded: with every step, the letters would have to get more complex. The evolution from (CG) to (CGUA) was propelled by spontaneous mutations: cytosine deamination and the oxidative guanine damage. This is the so-called process of the genome AT-enrichment. One can say that the evolution of the code was thermodynamically determined. Long chains consisting of guanine and cytosine could encode the first four amino acids: proline, glycine, alanine, and arginine. In all dialects of the genetic code, these amino acids are encoded by the same base pairs. If there were adaptors between mRNA and these amino acids, they were of a very simple structure. Deamination led to gradual accumulation of uracil, which was initially read as cytosine. Due to accumulation of a considerable amount of uracil the new base pairs – CU, UC, and GU – acquired meaning. The presence of similar amino acids that correspond to these strong base pairs (encoding only one amino acid) in all dialects is indicative of evolutionary antiquity of the base pairs and adaptors between mRNA and amino acids. The adaptors must have evolutionarily originated from their precursors and the amino acids were close to the antecedent ones in their chemical properties. The table of the genetic code base pairs should be filled starting with the four earliest and strongest base pairs and moving towards the four weakest and latest. Let us consider the table of the genetic code base pairs as it was proposed by Yu.B. Rumer in 1968 [2, 3] (Table 2). Color gradation illustrates the order of filling of the table cells: the darkest cells correspond to the most ancient base pairs.