Evidence from analyses of intergenic regions for strand-specific directional mutation pressure in metazoan mitochondrial DNA

The dynamic forces that determine the evolution of metazoan mitochondrial DNA (mtDNA) are analyzed. Using 24 completely sequenced genomes, we show that metazoan mtDNA is extremely economical with respect to the number of redundant nucleotides and that the intergenic DNA, that is, the nucleotides not included in genes, control regions, putative light-strand replication origins, and putative promoter-like motifs, varies considerably with respect to the A+C content-the A+C content of the intergenic mtDNA of Ascaris suum is equal to 0.169 ± 0.040 (SD), whereas that of Homo sapiens is equal to 0.804 ± 0.053. In agreement with previous reports that focus on the nucleotide composition of various informative parts of the metazoan mtDNA, we conclude that a significant strand-specific directional mutation pressure (P < 0.05) is exerted on the mtDNA of some species. Strand-specific directional mutation pressure in metazoan mtDNA may invalidate the most commonly used methods for estimating nucleotide substitution rates because these assume an unbiased nucleotide composition.