Mitochondrial DNA

Mitochondrial DNA (mtDNA) is the genetic material found inside mitochondria, the organelles in eukaryotic cells that convert chemical energy from organic compounds into ATP. While most of a cell’s DNA resides in the nucleus (and, in plants and algae, also in plastids like chloroplasts), mtDNA makes up only a small fraction. It codes for 13 essential subunits of the oxidative phosphorylation system, which is involved in cellular energy conversion.

Human mtDNA was the first major portion of the human genome to be sequenced, revealing 16,569 base pairs that encode 13 proteins. Like in other vertebrates, the human mitochondrial genetic code differs slightly from that of nuclear DNA. Because animal mtDNA evolves faster than nuclear genetic markers, it is a key tool in phylogenetics and evolutionary biology. It also helps trace population relationships, making it valuable in anthropology and biogeography.

**Origin** Nuclear and mitochondrial DNA are thought to have separate evolutionary origins. The endosymbiotic theory proposes that mtDNA derives from the circular genomes of bacteria engulfed by the ancestors of modern eukaryotic cells. Today, the vast majority of mitochondrial proteins (about 1,500 types in mammals) are coded by nuclear DNA, though many of those genes are believed to have bacterial origins and were transferred to the nucleus over evolution. Why mitochondria retain some genes is debated. Some species have mitochondrion-derived organelles without a genome, suggesting complete gene loss is possible, and transferring genes to the nucleus offers advantages. One hypothesis is that hydrophobic protein products are difficult to target remotely to the mitochondrion; another is that colocalization allows for localized redox regulation. Recent analysis of many mtDNA genomes suggests both factors may dictate which genes are retained.

**Genome structure and diversity** Across organisms, there are six main mitochondrial genome types, classified by structure (circular or linear), size, presence of introns or plasmid-like structures, and whether the genetic material is a single molecule or a collection of homogeneous or heterogeneous molecules. In many unicellular organisms (e.g., the ciliate *Tetrahymena* and the green alga *Chlamydomonas reinhardtii*), and rarely in multicellular ones (e.g., some Cnidaria), mtDNA is linear. Most linear mtDNAs have telomerase-independent telomeres with different replication modes, making them interesting research subjects since many such unicellular organisms are pathogens.

**Animals** Most bilaterian animals have a circular mitochondrial genome, though Medusozoa and Calcarea clades include species with linear chromosomes. With few exceptions, animals have 37 genes in their mtDNA: 13 for proteins, 22 for tRNAs, and 2 for rRNAs. Animal mitochondrial genomes average about 16,000 base pairs. The anemone *Isarachnanthus nocturnus* has the largest known animal mtDNA at 80,923 bp, while the comb jelly *Vallicula multiformis* has the smallest at 9,961 bp. In February 2020, a jellyfish-related parasite, *Henneguya salminicola*, was found to lack a mitochondrial genome entirely but retain mitochondrion-related organelles. Nuclear genes for aerobic respiration and mtDNA replication and transcription were either absent or pseudogenes, making it the first known multicellular organism to live completely without oxygen dependency. The crustacean *Armadillidium vulgare* has a uniquely large mtDNA—about 30 kb larger than average for crustaceans—making it a model organism in mtDNA research.

**Plants and fungi** Plants and fungi have three mitochondrial genome types. The first is a circular genome with introns (type 2), ranging from 19 to 1,000 kbp. The second is a circular genome (20–1,000 kbp) with a plasmid-like structure (1 kb) (type 3). The third is a linear genome of homogeneous DNA molecules (type 5). Gene content and size vary greatly among fungi and plants, though a core subset of genes appears in all eukaryotes (except those without mitochondria). In fungi, no single gene is shared among all mitogenomes. Some plants have enormous mitochondrial genomes; *Silene conica* mtDNA contains up to 11,300,000 base pairs, yet it has the same number and kinds of genes as related plants with much smaller mtDNAs. The cucumber (*Cucumis sativus*) has three circular mitochondrial chromosomes (1,556, 84, and 45 kilobases), each largely autonomous in replication.

**Protists** Protists have the most diverse mitochondrial genomes, with five different types. Types 2, 3, and 5 (found in plants and fungi) also occur in some protists, along with two unique types: a heterogeneous collection of circular DNA molecules (type 4) and a heterogeneous collection of linear molecules (type 6).