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

Abstract

AbstractTheoretical 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.