Nucleotide substitution rate of mammalian mitochondrial genomes

We present here for the first time a comprehensive study based on the analy sis of closely related organisms to provide an accurate determination of th e nucleotide substitution rate in mammalian mitochondrial genomes. This stu dy examines the evolutionary pattern of the different functional mtDNA regi ons as accurately as possible on the grounds of available data, revealing s ome important ''genomic laws.'' The main conclusions can be summarized as f ollows. (1) High intragenomic variability in the evolutionary dynamic of mt DNA was found. The substitution rate is strongly dependent on the region co nsidered, and slow- and fast-evolving regions can be identified. Nonsynonym ous sites, the D-loop central domain, and tRNA and tRNA genes evolve much m ore slowly than synonymous sites and the two peripheral D-loop region domai ns. The synonymous rate is fairly uniform over the genome, whereas the rate of nonsynonymous sites depends on functional constraints and therefore dif fers considerably between genes. (2) The commonly accepted statement that m tDNA evolves more rapidly than nuclear DNA is valid only for some regions, thus it should be referred to specific mitochondrial components. In particu lar, nonsynonymous sites show comparable rates in mitochondrial and nuclear genes; synonymous sites and small rRNA evolve about 20 times more rapidly and tRNAs about 100 times more rapidly in mitochondria than in their nuclea r counterpart. (3) A species-specific evolution is particularly evident in the D-loop region. As the divergence times of the organism pairs under cons ideration are known with sufficient accuracy, absolute nucleotide substitut ion rates are also provided.