Comparisons of DNA sequences in different organisms reveal that, in vertebrates (including ourselves), the mutation rate during evolution has been roughly 100 times greater in the mitochondrial genome than in the nuclear genome. This difference is likely to be due to lower fidelity of mitochondrial DNA replication,
Figure 14–63 A model for mitochondrial division. Dynamin-1 (yellow) exists as dimers in the cytosol, which form larger oligomeric structures in a process that requires Gtp hydrolysis. Dynamin assemblies interact with the outer mitochondrial membrane through special adaptor proteins, forming a spiral of Gtp-dynamin around the mitochondrion that causes a constriction. a concerted Gtp-hydrolysis event in the dynamin subunits is then thought to produce the conformational changes that result in fission. (adapted from S. hoppins, L. Lackner and J. Nunnari, Annu. Rev. Biochem. 76:751–780, 2007.) inefficient DNA repair, or both, given that the mechanisms that perform these processes in the organelle are relatively simple compared with those in the nucleus. As discussed in Chapter 4, the relatively high rate of evolution of animal mitochondrial genes makes a comparison of mitochondrial DNA sequences especially useful for estimating the dates of relatively recent evolutionary events, such as the steps in primate evolution.
There are 13 protein-encoding genes in human mitochondrial DNA (Figure 14–65). These code for hydrophobic components of the respiratory-chain complexes and of ATP synthase. In contrast, roughly 1000 mitochondrial proteins are encoded in the nucleus, produced on cytosolic ribosomes, and imported by the protein import machinery in the outer and inner membrane (discussed in Chapter 12). It has been suggested that the cytosolic production of hydrophobic membrane proteins and their import into the organelle may present a problem to the cell, and that this is the reason why their genes have remained in the mitochondrion. However, some of the most hydrophobic mitochondrial proteins, such as the c subunit of the ATP synthase rotor ring, are imported from the cytosol in some species (though they are mitochondrially encoded in others). And the parasites Plasmodium falciparum and Leishmania tarentolae, which spend most of their life cycles inside cells of their host organisms, have retained only two or three mitochondrially encoded proteins.
The size range of mitochondrial DNAs is similar to that of viral DNAs. The mitochondrial DNA in Plasmodium falciparum (the human malaria parasite) has less than 6000 nucleotide pairs, whereas the mitochondrial DNAs of some land plants contain more than 300,000 nucleotide pairs (Figure 14–66). In animals, the mitochondrial genome is a simple DNA circle of about 16,600 nucleotide pairs (less than 0.001% of the nuclear genome), and it is nearly the same size in organisms as different from us as Drosophila and sea urchins.
The human mitochondrial genome has several surprising features that distinguish it from nuclear, chloroplast, and bacterial genomes: 1.
Dense gene packing. Unlike other genomes, the human mitochondrial genome seems to contain almost no noncoding DNA: nearly every nucleotide seems to be part of a coding sequence, either for a protein or for one of the rRNAs or tRNAs. Since these coding sequences run directly into each other, there is very little room left for regulatory DNA sequences.
2.