Relationships between genomic base content and distribution of mass in coded proteins

The aim of this research was to examine the possible significance of genome/protein relationships in terms of effects on distribution of mass, especially in proteins. Amino acid residues in proteins have side-chains and polypeptide segments. We use "SCM" (side-chain mass), "MCM" (main-chain mass), and "deltaM" (SCM-MCM) as the deviation from "mass balance." Total MCM of the 61 amino acids in the standard code, 3412, equals total SCM: they form a mass balanced set (mean deltaM = 0). Of 14 natural variants of the code, seven have slightly positive mean deltaM values and seven have slightly negative values. Codes with the standard amino acids assigned randomly to the 20 codon sets of the standard code have about one chance in 3,300 of producing a mass balanced set. In natural proteins, as %A + T increases, the proportion of the mass in the side-chains also increases, by about half the amount calculated for standard genes with various AT/GC ratios, partly due to selection of codons with greater variability in composition at synonymous sites. For 203 representative species (including organelles), the total protein mass is distributed approximately equally between SCM and MCM (overall mean deltaM/amino acid residue, -0.06). The attainment of some overall macromolecular mass balance may have been a criterion for selecting the codon/amino acid pairs. When both structural and dynamic requirements are considered, a genetic code based on hydrophobicity and mass balance as key properties seems likely.