THE RATE HETEROGENEITY OF NONSYNONYMOUS SUBSTITUTIONS IN MAMMALIAN MITOCHONDRIAL GENES

Substitution rates at the three codon positions (r(1), r(2), and r(3)) of mammalian mitochondrial genes are in the order of r(3) > r(1) > r( 2), and the rate heterogeneity at the three positions, as measured by the shape parameter of the gamma distribution (alpha(1), alpha(2), and alpha(3)), is in the order of alpha(3) > alpha(1) > alpha(2). The cau ses for the rate heterogeneity at the three codon positions remain unc lear and, in particular, there has been no satisfactory explanation fo r the observation of alpha(1) > alpha(2). I attempted to dissect the c auses of rate heterogeneity by studying the pattern of nonsynonymous s ubstitutions with respect to codon positions in 10 mitochondrial genes from 19 mammalian species. Nonsynonymous substitutions involve more d ifferent amino acid replacements at the second than at the first codon position, which results in r(1) > r(2). The difference between r(1) a nd r(2) increases with the intensity of purifying selection, and so do es the rate heterogeneity in nonsynonymous substitutions among sites a t the same codon position. All mitochondrial genes appear to have func tionally important and unimportant codons, with the latter having all three codon positions prone to nonsynonymous substitutions. Within the functionally important codons, the second codon position is much more conservative than the codon position. This explains why alpha(1) > al pha(2). The result suggests that overweighting of the second codon pos ition in phylogenetic analysis may be a misguided practice.