The response of amino acid frequencies to directional mutation pressure in mitochondrial genome sequences is related to the physical properties of the amino acids and to the structure of the genetic code

The frequencies of A, C, G and T in mitochondrial DNA vary among species due to unequal rates of mutation between the bases. The frequencies of bases at four-fold degenerate sites respond directly to mutation pressure. At 1st and 2nd positions, selection reduces the degree of frequency variation. Using a simple evolutionary model, we show that 1st position sites are less constrained by selection than 2nd position sites, and therefore that the frequencies of bases at 1st position are more responsive to mutation pressure than those at 2nd position. We define a similarity measure between amino acids that is a function of 8 measured physical properties. We define a proximity measure for each amino acid, which is the average similarity between an amino acid and all others that are accessible via single point mutations in the genetic code. We also define a responsiveness for each amino acid, which measures how rapidly an amino acid frequency changes as a result of mutation pressure acting on the base frequencies. There is a strong correlation between responsiveness and proximity, and both these quantities are also correlated with the mutability of amino acids estimated from the mtREV substitution rate matrix. We also consider the variation of base frequencies between strands and between genes on a strand. These trends are consistent with the patterns expected from analysis of the variation among genomes