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

Abstract

Theoretical minimal RNA rings are candidate primordial genes evolved for non‐redundant coding of the genetic code's 22 coding signals (one codon per biogenic amino acid, a start and a stop codon) over the shortest possible length: 29520 22‐nucleotide‐long RNA rings solve this min‐max constraint. Numerous RNA ring properties are reminiscent of natural genes. Here we present analyses showing that all RNA rings lack dinucleotide CG (a mutable, chemically instable dinucleotide coding for Arginine), bearing a resemblance to known CG‐depleted genomes. CG in “incomplete” RNA rings (not coding for all coding signals, with only 3–12 nucleotides) gradually decreases towards CG absence in complete, 22‐nucleotide‐long RNA rings. Presumably, feedback loops during RNA ring growth during evolution (when amino acid assignment fixed the genetic code) assigned Arg to codons lacking CG (AGR) to avoid CG. Hence, as a chemical property of base pairs, CG mutability restructured the genetic code, thereby establishing itself as genetically encoded biological information.

The Ring World: Eversion of Small Double-Stranded Polynucleotide Circlets at the Origin of DNA Double Helix, RNA Polymerization, Triplet Code, Twenty Amino Acids, and Strand Asymmetry

“…Intriguingly, the sequences of the 25 primordial rings turn out to maximize the affinity between their nucleotide triplets and the corresponding cognate amino acids. Moreover, the calculated interactions between these RNA rings and their cognate peptides are strongest for ancient RNA rings and weakest for recent RNA rings, consistent with their putative role in pre-tRNA- to tRNA-mediated translation [ 51 , 52 , 53 ].…”

“…Given the importance attributed in the RNA world to a role for some peptide-free rRNA structure in translation, a specific prediction is that homologies should exist between the sequences of the AL-ring and its complement and modern rRNA (just as they do between the AL-ring and tRNA [ 53 ]. Such homologies actually exist; indeed, the most pentanucleotides in common with the AL-ring occur in the genes encoding the 5S proteins of Archaea, which are believed to be the oldest prokaryotes and which have a metabolism (like methanogenesis) that reflects Earth’s primitive atmosphere ( Supplementary Table S1 ).…”

Information Gradient among Nucleotide Sequences of Essential RNAs in an Evolutionary Perspective

“…When considering the primary structure of the tRNA loops of Archaea, the same pentameric sequences occurred first in many species like those belonging to the ancient Archaea studied in Figure 1 showing the following motifs: TGGTA for the D-loop, CTGCCA for the Anti-codon loop and TTCAA for the T -loop [33][34][35][36][37]. Exemples of such small sequences is given in Figure 1 and Table 2.…”

“…Some species whose tRNA-Gly GCC primary sequence have the same constant motifs in their loops [29,30]. From detailed studies [35][36][37], it appeared that pentamers or hexamers from AL could be remnants on the way to the progressive construction of nucleic acids involved in ribosome building and in mRNA of enzymes involved in ATP metabolism. Thus, following the concentration of these small sequences in many primitive species (Archaea or Bacteria) during the evolution makes it possible to obtain information on what could have happened during a long period when we do not have fossils or any other source of data.…”

Primitive Oligomeric RNAs at the Origins of Life on Earth

“…More recently, it was suggested to integrate the two theories with each other. DNA, enzymes and lipids were assumed to have interfered early with the engineering of the primitive RNAs [26] in order to give it a selective advantage over purely chemical systems [27][28][29][30][31][32][33][34][35][36]. This interpretation combines (i) the existence of a form of storage within primitive RNAs, also making it possible to promote peptide synthesis and the appearance of proto-genes consisting of combinations of fragments of primitive RNAs, (ii) the random inclusion of new RNA materials giving birth progressively to proteins ensuring biosynthesis and replication of DNA, (iii) the formation of lipid membranes compartmentalizing the spatial location of the functions (i) and (ii).…”