Universal Codons with Enrichment from GC to AU Nucleotide Composition Reveal a Chronological Assignment from Early to Late Along with LUCA Formation

Abstract

The emergence of a primitive genetic code should be considered the most essential event during the origin of life. Almost a complete set of codons (as we know them) should have been established relatively early during the evolution of the last universal common ancestor (LUCA) from which all known organisms descended. Many hypotheses have been proposed to explain the driving forces and chronology of the evolution of the genetic code; however, none is commonly accepted. In the current paper, we explore the features of the genetic code that, in our view, reflect the mechanism and the chronological order of the origin of the genetic code. Our hypothesis postulates that the primordial RNA was mostly GC-rich, and this bias was reflected in the order of amino acid codon assignment. If we arrange the codons and their corresponding amino acids from GC-rich to AU-rich, we find that: 1. The amino acids encoded by GC-rich codons (Ala, Gly, Arg, and Pro) are those that contribute the most to the interactions with RNA (if incorporated into short peptides). 2. This order correlates with the addition of novel functions necessary for the evolution from simple to longer folded peptides. 3. The overlay of aminoacyl-tRNA synthetases (aaRS) to the amino acid order produces a distinctive zonal distribution for class I and class II suggesting an interdependent origin. These correlations could be explained by the active role of the bridge peptide (BP), which we proposed earlier in the evolution of the genetic code.

Origin of Life: The Point of No Return

“…In that case, ordering the codons/anticodons from GC-rich toward AU-rich represents the chronological order of the amino acid assignment. If we align this order with the corresponding aminoacyl-tRNA synthetases (aaRS) for each amino acid, a very peculiar picture for the development of the genetic code and the corresponding aaRS emerged [46]. The observation shows a distinctive zonal distribution of aaRS for class II and class I along with the GC codon content.…”

“…The combination of increased A/U nucleotides in the RNA and the increased third nucleotide codon recognition opened the possibility for new codon combinations and amino acids assignment described in pre-LUCA II. In this hypothesis [46], the formation of the first codons is established as founding Darwinian evolution, i.e., only by the formation of coded amino acids did the system become more stable due to the newly formed positive feedback (Figure 1).…”

“…According to the mutual interdependence of these components, the origin of the genetic code and the origin of Darwinian evolution must have happened within the same interlinked process and cannot be explained separately. There are many hypotheses attempting to describe the formation of the universal genetic code [38][39][40][41][42][43][44][45][46]. It is not in the scope of the current paper to describe and analyze these hypotheses in detail, but only to emphasize their relevance to the definition of Darwinian evolution as shown in Figure 1.…”

“…The second type of hypotheses takes a different approach. The three nucleotide (two determinative plus one wobble) codon system was developed earlier than the entire set of coded amino acids with only a few amino acids [46]. We postulated that the nucleotide codon combination for any amino acid was determined by two major factors: the available nucleotide combinations not taken yet by previously coded amino acids and the physicochemical properties of the newly coded amino acid that would improve the chances of survival of the system during the codon assignment.…”

“…Later (during pre-LUCA II), class I aaRS begins its evolution with AU-rich codons along with the rest of class II. Pre-LUCA I was the time where the three-nucleotide coding translation apparatus was developed as a primitive structure with only few first coded amino acids [46]. Although all three nucleotides were part of the codon/anticodon recognition and were available, this logically would be a very primitive process with a low fidelity method of translation.…”