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Human mitochondrial DNA
Human mitochondrial DNA
with the 37 genes on their respective H- and L-strands.

Electron microscopy reveals mitochondrial DNA
DNA
in discrete foci. Bars: 200 nm. (A) Cytoplasmic section after immunogold labelling with anti-DNA; gold particles marking mt DNA
DNA
are found near the mitochondrial membrane (black dots in upper right). (B) Whole mount view of cytoplasm after extraction with CSK buffer and immunogold labelling with anti-DNA; mt DNA
DNA
(marked by gold particles) resists extraction. From Iborra et al., 2004.[2]

Mitochondrial DNA
DNA
(mt DNA
DNA
or mDNA)[3] is the DNA
DNA
located in mitochondria, cellular organelles within eukaryotic cells that convert chemical energy from food into a form that cells can use, adenosine triphosphate (ATP). Mitochondrial DNA
DNA
is only a small portion of the DNA
DNA
in a eukaryotic cell; most of the DNA
DNA
can be found in the cell nucleus and, in plants and algae, also in plastids such as chloroplasts. In humans, the 16,569 base pairs of mitochondrial DNA
DNA
encode for only 37 genes.[4] Human mitochondrial DNA
Human mitochondrial DNA
was the first significant part of the human genome to be sequenced. In most species, including humans, mt DNA
DNA
is inherited solely from the mother.[5] Since animal mt DNA
DNA
evolves faster than nuclear genetic markers,[6][7][8] it represents a mainstay of phylogenetics and evolutionary biology. It also permits an examination of the relatedness of populations, and so has become important in anthropology and biogeography.

Contents

1 Origin 2 Mitochondrial inheritance

2.1 Female inheritance 2.2 The mitochondrial bottleneck 2.3 Male inheritance 2.4 Mitochondrial donation

3 Structure

3.1 Circular versus linear 3.2 In mammals 3.3 In plants 3.4 In protists

4 Genome diversity

4.1 Animals 4.2 Plants and fungi 4.3 Protists

5 Replication 6 Transcription 7 Mutations and disease

7.1 Susceptibility 7.2 Genetic illness 7.3 Use in disease diagnosis 7.4 Relationship with aging 7.5 Correlation of the mt DNA
DNA
base composition with animals lifespan 7.6 Relationship with non-B (non-canonical) DNA
DNA
structures

8 Use in identification 9 History 10 Mitochondrial sequence databases 11 Mitochondrial mutation databases 12 See also 13 References 14 External links

Origin[edit] Nuclear and mitochondrial DNA
DNA
are thought to be of separate evolutionary origin, with the mt DNA
DNA
being derived from the circular genomes of the bacteria that were engulfed by the early ancestors of today's eukaryotic cells. This theory is called the endosymbiotic theory. Each mitochondrion is estimated to contain 2–10 mtDNA copies.[9] In the cells of extant organisms, the vast majority of the proteins present in the mitochondria (numbering approximately 1500 different types in mammals) are coded for by nuclear DNA, but the genes for some, if not most, of them are thought to have originally been of bacterial origin, having since been transferred to the eukaryotic nucleus during evolution.[10] The reasons why mitochondria have retained some genes are debated. The existence in some species of mitochondrion-derived organelles lacking a genome[11] suggests that complete gene loss is possible, and transferring mitochondrial genes to the nucleus has several advantages.[12] The difficulty of targeting remotely-produced hydrophobic protein products to the mitochondrion is one hypothesis for why some genes are retained in mtDNA;[13] colocalisation for redox regulation is another, citing the desirability of localised control over mitochondrial machinery.[14] Recent analysis of a wide range of mt DNA
DNA
genomes suggests that both these features may dictate mitochondrial gene retention.[10] Mitochondrial inheritance[edit] In most multicellular organisms, mt DNA
DNA
is inherited from the mother (maternally inherited). Mechanisms for this include simple dilution (an egg contains on average 200,000 mt DNA
DNA
molecules, whereas a healthy human sperm was reported to contain on average 5 molecules[15][16] ), degradation of sperm mt DNA
DNA
in the male genital tract, in the fertilized egg, and, at least in a few organisms, failure of sperm mt DNA
DNA
to enter the egg. Whatever the mechanism, this single parent (uniparental inheritance) pattern of mt DNA
DNA
inheritance is found in most animals, most plants and in fungi as well. Female inheritance[edit] In sexual reproduction, mitochondria are normally inherited exclusively from the mother; the mitochondria in mammalian sperm are usually destroyed by the egg cell after fertilization. Also, most mitochondria are present at the base of the sperm's tail, which is used for propelling the sperm cells; sometimes the tail is lost during fertilization. In 1999 it was reported that paternal sperm mitochondria (containing mtDNA) are marked with ubiquitin to select them for later destruction inside the embryo.[17] Some in vitro fertilization techniques, particularly injecting a sperm into an oocyte, may interfere with this. The fact that mitochondrial DNA
DNA
is maternally inherited enables genealogical researchers to trace maternal lineage far back in time. (Y-chromosomal DNA, paternally inherited, is used in an analogous way to determine the patrilineal history.) This is usually accomplished on human mitochondrial DNA
DNA
by sequencing the hypervariable control regions (HVR1 or HVR2), and sometimes the complete molecule of the mitochondrial DNA, as a genealogical DNA
DNA
test.[18] HVR1, for example, consists of about 440 base pairs. These 440 base pairs are then compared to the control regions of other individuals (either specific people or subjects in a database) to determine maternal lineage. Most often, the comparison is made to the revised Cambridge Reference Sequence. Vilà et al. have published studies tracing the matrilineal descent of domestic dogs to wolves.[19] The concept of the Mitochondrial Eve
Mitochondrial Eve
is based on the same type of analysis, attempting to discover the origin of humanity by tracking the lineage back in time. mt DNA
DNA
is highly conserved, and its relatively slow mutation rates (compared to other DNA
DNA
regions such as microsatellites) make it useful for studying the evolutionary relationships—phylogeny—of organisms. Biologists can determine and then compare mt DNA
DNA
sequences among different species and use the comparisons to build an evolutionary tree for the species examined. However, due to the slow mutation rates it experiences, it is often hard to distinguish between closely related species to any large degree, so other methods of analysis must be used. The mitochondrial bottleneck[edit] Entities undergoing uniparental inheritance and with little to no recombination may be expected to be subject to Muller's ratchet, the accumulation of deleterious mutations until functionality is lost. Animal populations of mitochondria avoid this buildup through a developmental process known as the mt DNA
DNA
bottleneck. The bottleneck exploits stochastic processes in the cell to increase in the cell-to-cell variability in mutant load as an organism develops: a single egg cell with some proportion of mutant mt DNA
DNA
thus produces an embryo where different cells have different mutant loads. Cell-level selection may then act to remove those cells with more mutant mtDNA, leading to a stabilisation or reduction in mutant load between generations. The mechanism underlying the bottleneck is debated,[20][21][22][23] with a recent mathematical and experimental metastudy providing evidence for a combination of random partitioning of mtDNAs at cell divisions and random turnover of mt DNA
DNA
molecules within the cell.[24] Male inheritance[edit] Main article: Paternal mt DNA
DNA
transmission Doubly uniparental inheritance of mt DNA
DNA
is observed in bivalve mollusks. In those species, females have only one type of mt DNA
DNA
(F), whereas males have F type mt DNA
DNA
in their somatic cells, but M type of mt DNA
DNA
(which can be as much as 30% divergent) in germline cells.[25] Paternally inherited mitochondria have additionally been reported in some insects such as fruit flies,[26][27] honeybees,[28] and periodical cicadas.[29] Male mitochondrial inheritance was recently discovered in Plymouth Rock chickens.[30] Evidence supports rare instances of male mitochondrial inheritance in some mammals as well. Specifically, documented occurrences exist for mice,[31][32] where the male-inherited mitochondria were subsequently rejected. It has also been found in sheep,[33] and in cloned cattle.[34] It has been found in a single case in a human male.[35] Although many of these cases involve cloned embryos or subsequent rejection of the paternal mitochondria, others document in vivo inheritance and persistence under lab conditions. Mitochondrial donation[edit] Main article: Mitochondrial donation An IVF technique known as mitochondrial donation or mitochondrial replacement therapy (MRT) results in offspring containing mt DNA
DNA
from a donor female, and nuclear DNA
DNA
from the mother and father. In the spindle transfer procedure, the nucleus of an egg is inserted into the cytoplasm of an egg from a donor female which has had its nucleus removed, but still contains the donor female's mtDNA. The composite egg is then fertilized with the male's sperm. The procedure is used when a woman with genetically defective mitochondria wishes to procreate and produce offspring with healthy mitochondria.[36] The first known child to be born as a result of mitochondrial donation was a boy born to a Jordanian couple in Mexico on 6 April 2016.[37] Structure[edit] Circular versus linear[edit] In most multicellular organisms, the mt DNA
DNA
– or mitogenome – is organized as a circular, covalently closed, double-stranded DNA. But in many unicellular (e.g. the ciliate Tetrahymena
Tetrahymena
or the green alga Chlamydomonas reinhardtii) and in rare cases also in multicellular organisms (e.g. in some species of Cnidaria
Cnidaria
) the mt DNA
DNA
is found as linearly organized DNA. Most of these linear mtDNAs possess telomerase independent telomeres (i.e. the ends of the linear DNA) with different modes of replication, which have made them interesting objects of research, as many of these unicellular organisms with linear mt DNA
DNA
are known pathogens.[38] In mammals[edit] For human mitochondrial DNA
DNA
(and probably for that of metazoans in general), 100–10,000 separate copies of mt DNA
DNA
are usually present per somatic cell (egg and sperm cells are exceptions). In mammals, each double-stranded circular mt DNA
DNA
molecule consists of 15,000–17,000[39] base pairs. The two strands of mt DNA
DNA
are differentiated by their nucleotide content, with a guanine-rich strand referred to as the heavy strand (or H-strand) and a cytosine-rich strand referred to as the light strand (or L-strand). The heavy strand encodes 28 genes, and the light strand encodes 9 genes for a total of 37 genes.[4] Of the 37 genes, 13 are for proteins (polypeptides), 22 are for transfer RNA
RNA
(tRNA) and two are for the small and large subunits of ribosomal RNA
RNA
(rRNA).[40] The human mitogenome contains overlapping genes (ATP8 and ATP6 as well as ND4L and ND4: see the human mitochondrial genome map), a feature that is rare in animal genomes.[citation needed] The 37-gene pattern is also seen among most metazoans, although in some cases one or more of these genes is absent and the mt DNA
DNA
size range is greater.

The 37 genes of the Cambridge Reference Sequence
Cambridge Reference Sequence
for human mitochondrial DNA
DNA
and their locations[40]

Gene Type Product Positions in the mitogenome Strand

MT-ATP8 protein coding ATP synthase, Fo subunit 8 (complex V) 08,366–08,572 (overlap with MT-ATP6) H

MT-ATP6 protein coding ATP synthase, Fo subunit 6 (complex V) 08,527–09,207 (overlap with MT-ATP8) H

MT-CO1 protein coding Cytochrome c
Cytochrome c
oxidase, subunit 1 (complex IV) 05,904–07,445 H

MT-CO2 protein coding Cytochrome c
Cytochrome c
oxidase, subunit 2 (complex IV) 07,586–08,269 H

MT-CO3 protein coding Cytochrome c
Cytochrome c
oxidase, subunit 3 (complex IV) 09,207–09,990 H

MT-CYB protein coding Cytochrome b
Cytochrome b
(complex III) 14,747–15,887 H

MT-ND1 protein coding NADH dehydrogenase, subunit 1 (complex I) 03,307–04,262 H

MT-ND2 protein coding NADH dehydrogenase, subunit 2 (complex I) 04,470–05,511 H

MT-ND3 protein coding NADH dehydrogenase, subunit 3 (complex I) 10,059–10,404 H

MT-ND4L protein coding NADH dehydrogenase, subunit 4L (complex I) 10,470–10,766 (overlap with MT-ND4) H

MT-ND4 protein coding NADH dehydrogenase, subunit 4 (complex I) 10,760–12,137 (overlap with MT-ND4L) H

MT-ND5 protein coding NADH dehydrogenase, subunit 5 (complex I) 12,337–14,148 H

MT-ND6 protein coding NADH dehydrogenase, subunit 6 (complex I) 14,149–14,673 L

MT-RNR2 protein coding Humanin — —

MT-TA transfer RNA tRNA- Alanine
Alanine
(Ala or A) 05,587–05,655 L

MT-TR transfer RNA tRNA- Arginine
Arginine
(Arg or R) 10,405–10,469 H

MT-TN transfer RNA tRNA- Asparagine
Asparagine
(Asn or N) 05,657–05,729 L

MT-TD transfer RNA tRNA- Aspartic acid
Aspartic acid
(Asp or D) 07,518–07,585 H

MT-TC transfer RNA tRNA- Cysteine
Cysteine
(Cys or C) 05,761–05,826 L

MT-TE transfer RNA tRNA- Glutamic acid
Glutamic acid
(Glu or E) 14,674–14,742 L

MT-TQ transfer RNA tRNA- Glutamine
Glutamine
(Gln or Q) 04,329–04,400 L

MT-TG transfer RNA tRNA- Glycine
Glycine
(Gly or G) 09,991–10,058 H

MT-TH transfer RNA tRNA- Histidine
Histidine
(His or H) 12,138–12,206 H

MT-TI transfer RNA tRNA- Isoleucine
Isoleucine
(Ile or I) 04,263–04,331 H

MT-TL1 transfer RNA tRNA- Leucine
Leucine
(Leu-UUR or L) 03,230–03,304 H

MT-TL2 transfer RNA tRNA- Leucine
Leucine
(Leu-CUN or L) 12,266–12,336 H

MT-TK transfer RNA tRNA- Lysine
Lysine
(Lys or K) 08,295–08,364 H

MT-TM transfer RNA tRNA- Methionine
Methionine
(Met or M) 04,402–04,469 H

MT-TF transfer RNA tRNA- Phenylalanine
Phenylalanine
(Phe or F) 00,577–00,647 H

MT-TP transfer RNA tRNA- Proline
Proline
(Pro or P) 15,956–16,023 L

MT-TS1 transfer RNA tRNA- Serine
Serine
(Ser-UCN or S) 07,446–07,514 L

MT-TS2 transfer RNA tRNA- Serine
Serine
(Ser-AGY or S) 12,207–12,265 H

MT-TT transfer RNA tRNA- Threonine
Threonine
(Thr or T) 15,888–15,953 H

MT-TW transfer RNA tRNA- Tryptophan
Tryptophan
(Trp or W) 05,512–05,579 H

MT-TY transfer RNA tRNA- Tyrosine
Tyrosine
(Tyr or Y) 05,826–05,891 L

MT-TV transfer RNA tRNA- Valine
Valine
(Val or V) 01,602–01,670 H

MT-RNR1 ribosomal RNA Small subunit : SSU (12S) 00,648–01,601 H

MT-RNR2 ribosomal RNA Large subunit : LSU (16S) 01,671–03,229 H

In plants[edit] Great variation in mt DNA
DNA
gene content and size exists among fungi and plants, although there appears to be a core subset of genes that are present in all eukaryotes (except for the few that have no mitochondria at all).[10] Some plant species have enormous mitochondrial genomes, with Silene conica
Silene conica
mt DNA
DNA
containing as many as 11,300,000 base pairs.[41] Surprisingly, even those huge mtDNAs contain the same number and kinds of genes as related plants with much smaller mtDNAs.[42] The genome of the mitochondrion of the cucumber (Cucumis sativus) consists of three circular chromosomes (lengths 1556, 84 and 45 kilobases), which are entirely or largely autonomous with regard to their replication.[43] In protists[edit] The smallest mitochondrial genome sequenced to date is the 5967 bp mt DNA
DNA
of the parasite Plasmodium falciparum.[44] Genome diversity[edit] There are six main genome types found in mitochondrial genomes, classified by their structure (e.g. circular versus linear), size, presence of introns or plasmid like structures, and whether the genetic material is a singular molecule or collection of homogeneous or heterogeneous molecules.[45] Animals[edit] There is only one mitochondrial genome type found in animal cells. This genome usually contains one circular molecule with between 11–28kbp of genetic material (type 1).[45] Plants and fungi[edit] There are three different genome types found in plants and fungi. The first type is a circular genome that has introns (type 2) and may range from 19–1000kbp in length. The second genome type is a circular genome (about 20–1000kbp) that also has a plasmid-like structure (1kb) (type 3). The final genome type that can be found in plant and fungi is a linear genome made up of homogeneous DNA molecules (type 5). Protists[edit] Protists contain the most diverse mitochondrial genomes, with five different types found in this kingdom. Type 2, type 3 and type 5 mentioned in the plant and fungal genomes also exists in some protist, as well as two unique genome types. The first of these is a heterogeneous collection of circular DNA
DNA
molecules (type 4) and the final genome type found in protists is a heterogeneous collection of linear molecules (type 6). Genome types 4 and 6 both range from 1–200kbp in size. Endosymbiotic gene transfer, the process of genes that were coded in the mitochondrial genome being transferred to the cell's main genome likely explains why more complex organisms, such as humans, have smaller mitochondrial genomes than simpler organisms, such as protists.

Genome Type[45] Kingdom Introns Size Shape Description

1 Animal No 11–28kbp Circular Single molecule

2 Fungi, Plant, Protista Yes 19–1000kbp Circular Single molecule

3 Fungi, Plant, Protista No 20–1000kbp Circular Large molecule and small plasmid like structures

4 Protista No 1–200kbp Circular Heterogeneous group of molecules

5 Fungi, Plant, Protista No 1–200kbp Linear Homogeneous group of molecules

6 Protista No 1–200kbp Linear Heterogeneous group of molecules

Replication[edit] Mitochondrial DNA
DNA
is replicated by the DNA
DNA
polymerase gamma complex which is composed of a 140 kDa catalytic DNA
DNA
polymerase encoded by the POLG
POLG
gene and two 55 kDa accessory subunits encoded by the POLG2 gene.[46] The replisome machinery is formed by DNA
DNA
polymerase, TWINKLE and mitochondrial SSB proteins. TWINKLE is a helicase, which unwinds short stretches of ds DNA
DNA
in the 5′ to 3′ direction.[47] During embryogenesis, replication of mt DNA
DNA
is strictly down-regulated from the fertilized oocyte through the preimplantation embryo.[48] The resulting reduction in per-cell copy number of mt DNA
DNA
plays a role in the mitochondrial bottleneck, exploiting cell-to-cell variability to ameliorate the inheritance of damaging mutations.[24] At the blastocyst stage, the onset of mt DNA
DNA
replication is specific to the cells of the trophectoderm.[48] In contrast, the cells of the inner cell mass restrict mt DNA
DNA
replication until they receive the signals to differentiate to specific cell types.[48] Transcription[edit] In animal mitochondria, each DNA
DNA
strand is transcribed continuously and produces a polycistronic RNA
RNA
molecule. Between most (but not all) protein-coding regions, tRNAs are present (see the human mitochondrial genome map). During transcription, the tRNAs acquire their characteristic L-shape that gets recognized and cleaved by specific enzymes. With the mitochondrial RNA
RNA
processing, individual mRNA, rRNA, and t RNA
RNA
sequences are released from the primary transcript.[49] Folded tRNAs therefore act as secondary structure punctuations.[50] Mutations and disease[edit]

Human mitochondrial DNA
Human mitochondrial DNA
with groups of protein-, rRNA- and tRNA-encoding genes.

The involvement of mitochondrial DNA
DNA
in several human diseases.

Susceptibility[edit] The concept that mt DNA
DNA
is particularly susceptible to reactive oxygen species generated by the respiratory chain due to its proximity remains controversial.[51] mt DNA
DNA
does not accumulate any more oxidative base damage than nuclear DNA.[52] It has been reported that at least some types of oxidative DNA
DNA
damage are repaired more efficiently in mitochondria than they are in the nucleus.[53] mt DNA
DNA
is packaged with proteins which appear to be as protective as proteins of the nuclear chromatin.[54] Moreover, mitochondria evolved a unique mechanism which maintains mt DNA
DNA
integrity through degradation of excessively damaged genomes followed by replication of intact/repaired mtDNA. This mechanism is not present in the nucleus and is enabled by multiple copies of mt DNA
DNA
present in mitochondria [55] The outcome of mutation in mt DNA
DNA
may be an alteration in the coding instructions for some proteins,[56] which may have an effect on organism metabolism and/or fitness. Genetic illness[edit] Further information: Mitochondrial disease Mutations of mitochondrial DNA
DNA
can lead to a number of illnesses including exercise intolerance and Kearns–Sayre syndrome
Kearns–Sayre syndrome
(KSS), which causes a person to lose full function of heart, eye, and muscle movements. Some evidence suggests that they might be major contributors to the aging process and age-associated pathologies.[57] Particularly in the context of disease, the proportion of mutant mtDNA molecules in a cell is termed heteroplasmy. The within-cell and between-cell distributions of heteroplasmy dictate the onset and severity of disease [58] and are influenced by complicated stochastic processes within the cell and during development.[24][59] Mutations in mitochondrial tRNAs can be responsible for severe diseases like the MELAS and MERRF syndromes.[60] Mutations in nuclear genes that encode proteins that mitochondria use can also contribute to mitochondrial diseases. These diseases do not follow mitochondrial inheritance patterns, but instead follow Mendelian inheritance patterns.[61] Use in disease diagnosis[edit] Recently a mutation in mt DNA
DNA
has been used to help diagnose prostate cancer in patients with negative prostate biopsy.[62][63] Relationship with aging[edit] Though the idea is controversial, some evidence suggests a link between aging and mitochondrial genome dysfunction.[64] In essence, mutations in mt DNA
DNA
upset a careful balance of reactive oxygen species (ROS) production and enzymatic ROS scavenging (by enzymes like superoxide dismutase, catalase, glutathione peroxidase and others). However, some mutations that increase ROS production (e.g., by reducing antioxidant defenses) in worms increase, rather than decrease, their longevity.[51] Also, naked mole rats, rodents about the size of mice, live about eight times longer than mice despite having reduced, compared to mice, antioxidant defenses and increased oxidative damage to biomolecules.[65] Once, there was thought to be a positive feedback loop at work (a 'Vicious Cycle'); as mitochondrial DNA
DNA
accumulates genetic damage caused by free radicals, the mitochondria lose function and leak free radicals into the cytosol. A decrease in mitochondrial function reduces overall metabolic efficiency.[66] However, this concept was conclusively disproved when it was demonstrated that mice, which were genetically altered to accumulate mt DNA
DNA
mutations at accelerated rate do age prematurely, but their tissues do not produce more ROS as predicted by the 'Vicious Cycle' hypothesis.[67] Supporting a link between longevity and mitochondrial DNA, some studies have found correlations between biochemical properties of the mitochondrial DNA
DNA
and the longevity of species.[68] Extensive research is being conducted to further investigate this link and methods to combat aging. Presently, gene therapy and nutraceutical supplementation are popular areas of ongoing research.[69][70] Bjelakovic et al. analyzed the results of 78 studies between 1977 and 2012, involving a total of 296,707 participants, and concluded that antioxidant supplements do not reduce all-cause mortality nor extend lifespan, while some of them, such as beta carotene, vitamin E, and higher doses of vitamin A, may actually increase mortality.[71] Correlation of the mt DNA
DNA
base composition with animals lifespan[edit]

Animal species mt DNA
DNA
base composition was retrieved from the MitoAge database and compared to their maximum life span from AnAge database.

Over the past decade, an Israeli research group led by Professor Vadim Fraifeld has shown that extraordinarily strong and significant correlations exist between the mt DNA
DNA
base composition and animal species-specific maximum life spans.[72][73][74] As demonstrated in their work, higher mt DNA
DNA
guanine + cytosine content (GC%) strongly associates with longer maximum life spans across animal species. An additional astonishing observation is that the mt DNA
DNA
GC% correlation with the maximum life spans is independent of the well-known correlation between animal species metabolic rate and maximum life spans. The mt DNA
DNA
GC% and resting metabolic rate explain the differences in animal species maximum life spans in a multiplicative manner (i.e., species maximum life span = their mt DNA
DNA
GC% * metabolic rate).[73] To support the scientific community in carrying out comparative analyses between mt DNA
DNA
features and longevity across animals, a dedicated database was built named MitoAge.[75] Relationship with non-B (non-canonical) DNA
DNA
structures[edit] Deletion breakpoints frequently occur within or near regions showing non-canonical (non-B) conformations, namely hairpins, cruciforms and cloverleaf-like elements.[76] Moreover, there is data supporting the involvement of helix-distorting intrinsically curved regions and long G-tetrads in eliciting instability events. In addition, higher breakpoint densities were consistently observed within GC-skewed regions and in the close vicinity of the degenerate sequence motif YMMYMNNMMHM.[77] Recently (2017) was found that all mitochodrial genomes sequenced so far contain many of inverted repeats necessary for cruciform DNA
DNA
formation and these loci are particularly enriched in replication origin sites, D-loops and stem loops.[78] Use in identification[edit] For use in human identification, see Human
Human
mitochondrial DNA. Unlike nuclear DNA, which is inherited from both parents and in which genes are rearranged in the process of recombination, there is usually no change in mt DNA
DNA
from parent to offspring. Although mt DNA
DNA
also recombines, it does so with copies of itself within the same mitochondrion. Because of this and because the mutation rate of animal mt DNA
DNA
is higher than that of nuclear DNA,[79] mt DNA
DNA
is a powerful tool for tracking ancestry through females (matrilineage) and has been used in this role to track the ancestry of many species back hundreds of generations. The rapid mutation rate (in animals) makes mt DNA
DNA
useful for assessing genetic relationships of individuals or groups within a species and also for identifying and quantifying the phylogeny (evolutionary relationships; see phylogenetics) among different species. To do this, biologists determine and then compare the mt DNA
DNA
sequences from different individuals or species. Data from the comparisons is used to construct a network of relationships among the sequences, which provides an estimate of the relationships among the individuals or species from which the mtDNAs were taken. mt DNA
DNA
can be used to estimate the relationship between both closely related and distantly related species. Due to the high mutation rate of mt DNA
DNA
in animals, the 3rd positions of the codons change relatively rapidly, and thus provide information about the genetic distances among closely related individuals or species. On the other hand, the substitution rate of mt-proteins is very low, thus amino acid changes accumulate slowly (with corresponding slow changes at 1st and 2nd codon positions) and thus they provide information about the genetic distances of distantly related species. Statistical models that treat substitution rates among codon positions separately, can thus be used to simultaneously estimate phylogenies that contain both closely and distantly related species[60] Mitochondrial DNA
DNA
was admitted into evidence for the first time ever in 1996 during State of Tennessee v. Paul Ware.[80] In the 1998 court case of Commonwealth of Pennsylvania v. Patricia Lynne Rorrer,[81] mitochondrial DNA
DNA
was admitted into evidence in the State of Pennsylvania for the first time.[82][83] The case was featured in episode 55 of season 5 of the true crime drama series Forensic Files (season 5).[citation needed] Mitochondrial DNA
DNA
was first admitted into evidence in California
California
in the successful prosecution of David Westerfield for the 2002 kidnapping and murder of 7-year-old Danielle van Dam in San Diego: it was used for both human and dog identification.[84] This was the first trial in the U.S. to admit canine DNA.[85] The remains of King Richard III were identified by comparing his mtDNA with that of two matrilineal descendants of his sister.[86] History[edit] Mitochondrial DNA
DNA
was discovered in the 1960s by Margit M. K. Nass and Sylvan Nass by electron microscopy as DNase-sensitive threads inside mitochondria,[87] and by Ellen Haslbrunner, Hans Tuppy
Hans Tuppy
and Gottfried Schatz by biochemical assays on highly purified mitochondrial fractions.[88] Mitochondrial sequence databases[edit] Several specialized databases have been founded to collect mitochondrial genome sequences and other information. Although most of them focus on sequence data, some of them include phylogenetic or functional information.

MitoSatPlant: Mitochondrial microsatellites database of viridiplantae.[89] MitoBreak: the mitochondrial DNA
DNA
breakpoints database.[90] MitoFish and MitoAnnotator: a mitochondrial genome database of fish.[91] See also Cawthorn et al.[92] MitoZoa 2.0: a database for comparative and evolutionary analyses of mitochondrial genomes in Metazoa.[93] (no longer available) InterMitoBase: an annotated database and analysis platform of protein-protein interactions for human mitochondria.[94] (apparently last updated in 2010, but still available) Mitome: a database for comparative mitochondrial genomics in metazoan animals[95] (no longer available) MitoRes: a resource of nuclear-encoded mitochondrial genes and their products in metazoa[96] (apparently no longer being updated)

Mitochondrial mutation databases[edit] Several specialized databases exist that report polymorphisms and mutations in the human mitochondrial DNA, together with the assessment of their pathogenicity.

MITOMAP: A compendium of polymorphisms and mutations in human mitochondrial DNA
DNA
[3]. MitImpact: A collection of pre-computed pathogenicity predictions for all nucleotide changes that cause non-synonymous substitutions in human mitochondrial protein coding genes [4].

See also[edit]

Archaeogenetics of the Near East Clade CoRR hypothesis Haplogroup Heteroplasmy Human mitochondrial DNA
Human mitochondrial DNA
haplogroup Human
Human
mitochondrial genetics Mitochondrial disease Mitochondrial DNA
DNA
(journal) Mitochondrial Eve Mitochondrial rCRS Paternal mt DNA
DNA
transmission Single origin theory Supercluster (genetic) TIM/TOM complex Genetic history of Africa Genetic history of Europe Genetic history of the British Isles Genetic history of the Iberian Peninsula Genetic history of indigenous peoples of the Americas Genetic history of Italy Genetic history of North Africa Genetics and archaeogenetics of South Asia

References[edit]

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DNA
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Human
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External links[edit]

Media related to Mitochondrial DNA
DNA
at Wikimedia Commons

v t e

Human
Human
genome

Nuclear genome

Autosome

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22

Sex chromosome

X Y

Mitochondrial genome

Human
Human
mitochondrial DNA

v t e

Types of nucleic acids

Constituents

Nucleobases Nucleosides Nucleotides Deoxynucleotides

Ribonucleic acids (coding, non-coding)

Translational

Messenger

precursor, heterogenous nuclear

Transfer Ribosomal Transfer-messenger

Regulatory

Interferential

Micro Small interfering Piwi-interacting

Antisense Processual

Small nuclear Small nucleolar Small Cajal Body RNAs Y RNA

Enhancer RNAs

Others

Guide Ribozyme Small hairpin Small temporal Trans-acting small interfering Subgenomic messenger

Deoxyribonucleic acids

Complementary Chloroplast Deoxyribozyme Genomic Multicopy single-stranded Mitochondrial

Analogues

Xeno

Glycol Threose Hexose

Locked Peptide Morpholino

Cloning vectors

Phagemid Plasmid Lambda phage Cosmid Fosmid Artificial chromosomes

P1-derived Bacterial Yeast Human

v t e

Mitochondrial proteins

Outer membrane

fatty acid degradation

Carnitine palmitoyltransferase I Long-chain-fatty-acid—CoA ligase

tryptophan metabolism

Kynureninase

monoamine neurotransmitter metabolism

Monoamine oxidase

Intermembrane space

Adenylate kinase Creatine kinase

Inner membrane

oxidative phosphorylation

Coenzyme Q – cytochrome c reductase Cytochrome c NADH dehydrogenase Succinate dehydrogenase

pyrimidine metabolism

Dihydroorotate dehydrogenase

mitochondrial shuttle

Malate-aspartate shuttle Glycerol phosphate shuttle

other

Glutamate aspartate transporter Glycerol-3-phosphate dehydrogenase ATP synthase Carnitine palmitoyltransferase II Uncoupling protein

Matrix

citric acid cycle

Citrate synthase Aconitase Isocitrate dehydrogenase Oxoglutarate dehydrogenase complex Succinyl coenzyme A synthetase Fumarase Malate dehydrogenase

anaplerotic reactions

Aspartate transaminase Glutamate dehydrogenase Pyruvate dehydrogenase complex

urea cycle

Carbamoyl phosphate synthetase I Ornithine transcarbamylase N-Acetylglutamate synthase

alcohol metabolism

ALDH2

PMPCB

Other/to be sorted

steroidogenesis

Cholesterol side-chain cleavage enzyme Steroid 11-beta-hydroxylase Aldosterone synthase Frataxin

Mitochondrial membrane transport protein

Mitochondrial permeability transition pore Mitochondrial carrier

Mitochondrial DNA

Complex I

MT-ND1 MT-ND2 MT-ND3 MT-ND4 MT-ND4L MT-ND5 MT-ND6

Complex III

MT-CYB

Complex IV

MT-CO1 MT-CO2 MT-CO3

ATP synthase

MT-ATP6 MT-ATP8

tRNA

MT-TA MT-TC MT-TD MT-TE MT-TF MT-TG MT-TH MT-TI MT-TK MT-TL1 MT-TL2 MT-TM MT-TN MT-TP MT-TQ MT-TR MT-TS1 MT-TS2 MT-TT MT-TV MT-TW MT-TY

see also mitochondrial diseases

Authority control

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