Nucleotide Substitution Rate of Mammalian Mitochondrial Genomes

Abstract

We present here for the first time a comprehensive study based on the analysis of closely related organisms to provide an accurate determination of the nucleotide substitution rate in mammalian mitochondrial genomes. This study examines the evolutionary pattern of the different functional mtDNA regions as accurately as possible on the grounds of available data, revealing some important "genomic laws." The main conclusions can be summarized as follows. (1) High intragenomic variability in the evolutionary dynamic of mtDNA was found. The substitution rate is strongly dependent on the region considered, and slow- and fast-evolving regions can be identified. Nonsynonymous sites, the D-loop central domain, and tRNA and rRNA genes evolve much more slowly than synonymous sites and the two peripheral D-loop region domains. The synonymous rate is fairly uniform over the genome, whereas the rate of nonsynonymous sites depends on functional constraints and therefore differs considerably between genes. (2) The commonly accepted statement that mtDNA evolves more rapidly than nuclear DNA is valid only for some regions, thus it should be referred to specific mitochondrial components. In particular, 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 nuclear counterpart. (3) A species-specific evolution is particularly evident in the D-loop region. As the divergence times of the organism pairs under consideration are known with sufficient accuracy, absolute nucleotide substitution rates are also provided.

Comparing Evolutionary Patterns and Variability in the Mitochondrial Control Region and Cytochrome b in Three Species of Baleen Whales

“…Using this method, substitution rates were 4.8% (4.32-5.36%), 4.6% (3.59-5.5%), and 4.4% (4.0-4.69%) per Myr for gray, humpback, and minke, respectively. Regardless of the method used, all rates are significantly higher than control region substitution rates estimated from divergence dates using the fossil record (e.g., Pesole et al 1999;Rooney et al 2001;Roman and Palumbi 2003), which range from 1.5% to 2% per Myr. Although no error estimates are available for earlier rates, confidence intervals for cytochrome b calibrated rates do not approach these earlier values.…”

“…We first scaled all H values for cytochrome b and the control region by their appropriate (phylogenetically derived) mutation rates in order to account for functional constraints on evolutionary rate (resulting in units of Ne), since any relative constraints due to function should be reflected in substitution rates. The evolutionary rate of different segments of the mitochondrial genome in whales and other mammals has previously been estimated by comparing genetic distance between species at a given marker against divergence dates for those species (Pesole et al 1999;Roman and Palumbi 2003). Phylogenetic analyses indicate that the control region is evolving at a rate of roughly 1.5-2% per million years (Myr) in whales (Pesole et al 1999;Roman and Palumbi 2003), and cytochrome b is evolving at a rate of about 0.4% per Myr (Alter et al 2007).…”

“…The evolutionary rate of different segments of the mitochondrial genome in whales and other mammals has previously been estimated by comparing genetic distance between species at a given marker against divergence dates for those species (Pesole et al 1999;Roman and Palumbi 2003). Phylogenetic analyses indicate that the control region is evolving at a rate of roughly 1.5-2% per million years (Myr) in whales (Pesole et al 1999;Roman and Palumbi 2003), and cytochrome b is evolving at a rate of about 0.4% per Myr (Alter et al 2007). Therefore, we scaled H values using rates of 0.4% per Myr per bp for cytochrome b and a rate of 2% per Myr per bp for the control region (Roman and Palumbi 2003).…”

Mitonuclear coevolution as the genesis of speciation and the mitochondrial DNA barcode gap

“…Interestingly, COX1 and other mitochondrial‐encoded cytochrome c oxidase genes are the least variable of all mitochondrial genes (Pesole et al. 1999; da Fonseca et al. 2008), apparently subject to strong purifying selection and functional constraint (Kerr 2011).…”

A comparison of mitochondrial and nuclear DNA status in testicular sperm from fertile men and those with obstructive azoospermia

“…Bohr and Dianov have reported that this mechanism can repair excision and bases caused by oxidative insult (Bohr and Dianov, 1999). The mitochondrion also replicates rapidly, without a significant proofreading system and has a mutation rate 10-100 times higher than that of nuclear DNA (nDNA) (Pesole et al, 1999).…”