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

Abstract

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 1 st and 2 nd positions, selection reduces the degree of frequency variation. Using a simple evolutionary model, we show that 1 st position sites are less constrained by selection than 2 nd position sites, and therefore that the frequencies of bases at 1 st position are more responsive to mutation pressure than those at 2 nd position. We define a measure of distance between amino acids that is dependent on 8 measured physical properties, and a similarity measure that is the inverse of this distance. Columns 1, 2 3 and 4 of the genetic code correspond to codons with U, C, A and G in their 2 nd position, respectively. The similarity of amino acids in the four columns decreases systematically from column 1 to 2 to 3 to 4. We then show that the responsiveness of 1 st position bases to mutation pressure is dependent on the 2 nd position base, and follows the same decreasing trend through the four columns. Again, thisshows the correlation between physical properties and responsiveness. We determine 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 mitochondrial genetic code structure. 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.We show that there is a strong correlation between responsiveness and proximity, and that 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.

Directionality in the evolution of influenza A haemagglutinin

“…Indeed, non-synonymous changes at the second amino acid position tend to change the properties of the encoded amino acid more radically than non-synonymous changes at the first or third positions (e.g. Haig & Hurst 1991;Urbina et al 2006). …”

The Mechanisms of Codon Reassignments in Mitochondrial Genetic Codes

“…$\end{document}. In mitochondrial genomes, the two strands of the genome are not equivalent, the four base frequencies are all different, and it is not true that π C = π G and π A = π U (see Urbina et al 2006). The values of the frequencies can be estimated from the frequencies of the bases at fourfold degenerate (FFD) sites.…”

An Evolutionary Footprint of Age-Related Natural Selection in Mitochondrial DNA

“…First, we can discount the possibility that the decreased numbers of threonines in the human lineage is simply a reflection of the increased GC content. Although nucleotide content does affect mt amino acid content (Foster et al 1997), the correlation between the GC content and the frequency of threonine residues is generally positive (Urbina et al 2006), whereas in the humanchimpanzee comparison we see a decrease in threonine residues despite an increase in overall GC content. There is also independent experimental evidence for the action of selection in this case.…”