Mitochondrial Genome

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Mitochondrial Genome

One of the defining features of eukaryotic cells is the presence of membrane-enclosed organelles. Two of these organelles, the mitochondria and chloroplast, are unique in that they contain their own genetic material necessary for proper functioning. These organelle genomes are evolutionary relics of free-living bacteria that entered into a symbiotic relationship with a host cell. Through the process of cellular respiration, mitochondria produce about 90 percent of the chemical energy that a cell needs to survive. The discovery that mutations in the mitochondrial genome can cause a variety of human diseases has increased our interest in this "other" human genome.

Organelle Structure and Energy Production

The mitochondria (singular: mitochondrion) are enclosed by two membranes, each a phospholipid bilayer with a unique collection of embedded proteins. The outer membrane is smooth, but the inner membrane contains extensive folds called cristae. The cristae provide a means of packing a relatively large amount of the inner membrane into a very small container, thus enhancing the productivity of cellular respiration. The number of mitochondria per cell is correlated with the cell's level of metabolic activity, with a typical cell containing hundreds to thousands of these organelles. Time-lapse photography of living cells reveals mitochondria as very dynamic structures, moving around, changing shape, and dividing.

Often described as the "power plant" of the cell, mitochondria generate ATP by extracting energy from sugar, fats, and other fuels with the help of oxygen. Mitochondria generate most of the energy in animal cells through a process called oxidative phosphorylation. In this process, electrons are passed along a series of protein complexes that are located in the inner mitochondrial membrane. The passage of electrons between these protein complexes releases energy that is stored in the membrane, and is then used to make ATP from ADP.

Mitochondrial DNA: Function and Replication

Scientists have known since the early 1960s that the nucleus is not the only location for DNA in a eukaryotic cell. The mitochondria (and the chloroplasts in plant cells) harbor their own small genome. The genes found on the circular 16,569 base-pair piece of mitochondrial DNA (mtDNA) in human cells code for thirteen proteins, two ribosomal RNAs (rRNA), and twenty-two transfer RNAs (tRNAs), all of which are essential for the production of ATP by the mitochondria. Each individual organelle contains several copies of the mitochondrial genome. Although they comprise only a small portion of the proteins found in the mitochondrion, all thirteen proteins encoded by the mtDNA are essential, because they are necessary for oxidative phosphorylation and the production of cellular ATP. All of the remaining mitochondrial components are encoded by nuclear genes and are imported into the organelle.

The mitochondrial genome in mammals is extremely compact, with essentially no introns and very little DNA sequence between genes. Each of the protein and rRNA genes is immediately flanked by tRNA genes. Initial transcription of mtDNA produces large RNA molecules that are then processed into smaller units to generate mature tRNAs, rRNAs, and mRNAs.

The two mtDNA strands in the circular molecule can be separated based on their density (due to their differing nucleotide compositions), and are thus designated as the heavy strand (H-strand) and the light strand (L-strand). Both strands are transcribed completely, making two long RNA molecules. Since the two strands are complementary (not identical), they do not each code for the same genes. Instead, the H-strand transcript codes for most of the proteins and tRNAs, while the L-strand codes for most of the rRNAs. Ninety percent of the L-strand does not code for useful products, and is degraded after it is transcribed. The processed L-strand transcript also functions as the starting point for replication of the mitochondrial chromosome.

Endosymbiosis and Genome Reduction

Given the bacterial-like features of mitochondria and chloroplasts (small size, circular genome, and ability to divide on their own), it is believed that each organelle traces its evolutionary history to a free-living bacterial ancestor that was engulfed by a larger cell and then entered into a symbiotic relationship with the host cell. This "serial endosymbiotic theory" proposes that the evolution of the modern eukaryotic cell was a step-wise association, with the acquisition of the mitochondria preceding that of the chloroplast. The most compelling evidence for the endosymbiosis theory has come from the analysis of complete genome sequences. Comparison of DNA sequence data has identified two specific groups of bacteria, α-Proteobacteria and Cyanobacteria, as the closest living relatives of mitochondria and chloroplasts, respectively. The mtDNA sequence information from numerous organisms has revealed remarkable similarity, reinforcing the idea of a single primary ancestor for the organelle originating very early in the evolution of the eukaryotic cell.

During the course of evolution, a large portion of mitochondrial genes were either lost or transferred to the nuclear genome . Elimination of genes from mtDNA is an ongoing evolutionary process made possible because their functions either become dispensable or can be replaced by nuclear functions. A comparison of the complete mtDNA sequence and the working draft of the human nuclear genome project reveals numerous areas of similarity. These regions represent mtDNA sequences that have been transferred from the cytoplasm to the nucleus over the course of mammalian evolution. This transfer accounts for the current nuclear location of most of the genes that encode mitochondrial proteins, including most of the proteins required for oxidative phosphorylation. Even eukaryotes that lack mitochondria (such as some protists) contain nuclear genes that encode typical mitochondrial proteins, implying that these eukaryoytes once had mitochondria but subsequently lost them.

see also Cell, Eukaryotic; Eubacteria; Inheritance, Extranuclear; Mitochondrial Diseases; Molecular Anthropology.

Stephan Zweifel


Wallace, Douglas C. "Mitochondrial DNA in Aging and Disease." Scientific American 277, no. 2 (1997): 40-47.

"Special Section: Mitochondria." Science 283 (1999): 1475-1497. (A series of articles on the mitochondrial genome, mtDNA diseases, and the evolution of the organelle.)

Internet Resource

MITOMAP (a human mitochondrial genome database). Center for Molecular Medicine, Emory University. <>.