The Pattern of Occurrence of Cytosine in the Genetic Code Minimizes Deleterious Mutations and Favors Proper Function of the Translational Machinery

The standard genetic code consists of 64 combinations of base triplets made from four different bases. The research aim of this study was to investigate the pattern of occurrence of cytosine in the genetic code. By exploring the base composition and sequence of all 64 codons, the author found some important features based on the instability of cytosine. Because cytosine undergoes spontaneous deamination that converts it into uracil, it is evolutionarily favorable to exclude cytosine from codons critical to the initiation and termination of translation. For amino acids that have one to three synonymous codons (also called synonyms), the frequency of occurrence of C in the first and second positions of their mRNA codons is significantly lower than the frequencies of A, U, and G. For mRNA codons that encode amino acids with four synonyms, the trend of base composition is opposite to those encoding amino acids with one to three synonyms; the instability of C could be inhibited or reduced via formation of hydrogen bonds with a G and/or with a protonated C, and the secondary structure of the resultant mRNA could be adjusted via the multiple synonymous alternates at the third position of their codons to facilitate the translation process. The overall pattern of occurrence for C in the genetic code not only minimizes deleterious mutations and favors proper function of the translational machinery by excluding C from certain positions within codons, but also allows the occurrence of genetic diversity via mutation by including C in less-critical positions.