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 |
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Authors: | Daniel Urbina Bin Tang Paul G Higgs |
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Affiliation: | (1) Department of Physics and Astronomy, McMaster University, Main Street West, Hamilton, Ontario, L8S 4M1, Canada;(2) Division of Genomics and Proteomics, Ontario Cancer Institute, University of Toronto, Suite 703, 620 University Avenue, Toronto, Ontario, M5G 2M9, Canada |
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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 fourfold degenerate sites respond directly to mutation pressure. At first and second positions,
selection reduces the degree of frequency variation. Using a simple evolutionary model, we show that first position sites
are less constrained by selection than second position sites and, therefore, that the frequencies of bases at first position
are more responsive to mutation pressure than those at second position. We define a measure of distance between amino acids
that is dependent on eight 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 second position, respectively. The similarity
of amino acids in the four columns decreases systematically from column 1 to column 2 to column 3 to column 4. We then show
that the responsiveness of first position bases to mutation pressure is dependent on the second position base and follows
the same decreasing trend through the four columns. Again, this shows 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.
Reviewing Editor: Dr. David Pollock] |
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Keywords: | Mitochondrial genomes Directional mutation pressure Genetic code Amino acid substitutions |
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