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 mitochondr ial DNA (mtDNA) are analyzed. Using 24 completely sequenced genomes, w e 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 ligh t-strand replication origins, and putative promoter-like motifs, varie s considerably with respect to the ASC content-the A+C content of the intergenic mtDNA of Ascaris suum is equal to 0.169 +/- 0.040 (SD), whe reas that of Homo sapiens is equal to 0.804 +/- 0.053. In agreement wi th previous reports that focus on the nucleotide composition of variou s informative parts of the metazoan mtDNA, we conclude that a signific ant strand-specific directional mutation pressure (P < 0.05) is exerte d on the mtDNA of some species. Strand-specific directional mutation p ressure in metazoan mtDNA may invalidate the most commonly used method s for estimating nucleotide substitution rates because these assume an unbiased nucleotide composition.