On the Importance of Asymmetry in the Phenotypic Expression of the Genetic Code upon the Molecular Evolution of Proteins

Abstract

The standard genetic code (SGC) is a mapping between the 64 possible arrangements of the four RNA nucleotides (C, A, U, G) into triplets or codons, where 61 codons are assigned to a specific amino acid and the other three are stop codons for terminating protein synthesis. Aminoacyl-tRNA synthetases (aaRSs) are responsible for implementing the SGC by specifically amino-acylating only its cognate transfer RNA (tRNA), thereby linking an amino acid with its corresponding anticodon triplets. tRNAs molecules bind each codon with its anticodon. To understand the meaning of symmetrical/asymmetrical properties of the SGC, we designed synthetic genetic codes with known symmetries and with the same degeneracy of the SGC. We determined their impact on the substitution rates for each amino acid under a neutral model of protein evolution. We prove that the phenotypic graphs of the SGC for codons and anticodons for all the possible arrangements of nucleotides are asymmetric and the amino acids do not form orbits. In the symmetrical synthetic codes, the amino acids are grouped according to their codonicity, this is the number of triplets encoding a given amino acid. Both the SGC and symmetrical synthetic codes exhibit a probability of occurrence of the amino acids proportional to their degeneracy. Unlike the SGC, the synthetic codes display a constant probability of occurrence of the amino acid according to their codonicity. The asymmetry of the phenotypic graphs of codons and anticodons of the SGC, has important implications on the evolutionary processes of proteins.

Symmetrical distributions of aminoacyl-tRNA synthetases during the evolution of the genetic code

“…The SGC has been modeled in a 6D hypercube using group theory (José and Zamudio 2020 ; Sethuraman 1997 ). The vertices of the hypercube represent the 64 possible nucleotide triplets and the edges join triplets that differ by one nucleotide under different arrangements of the nucleotides in a square (José and Zamudio 2020 ).…”

“…The SGC has been modeled in a 6D hypercube using group theory (José and Zamudio 2020 ; Sethuraman 1997 ). The vertices of the hypercube represent the 64 possible nucleotide triplets and the edges join triplets that differ by one nucleotide under different arrangements of the nucleotides in a square (José and Zamudio 2020 ). Each of the three possible arrangements of the nucleotides in a square produces different orderings of the codon triplets in the hypercube (José and Zamudio 2020 ); a fourth arrangement of the nucleotides is given by the square with its two diagonals, representing a scenario where all possible nucleotide changes are within reach in one-step mutation.…”