Mitochondrial DNA
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[[Image:Mitochondrial DNA en.svg|thumb|300px|right|Mitochondrial DNA.]]
'''Mitochondrial DNA''' ('''mtDNA''') is the [[DNA]] located in [[organelles]] called [[mitochondrion|mitochondria]]. Most other DNA present in [[eukaryotic]] organisms is found in the [[cell nucleus]]. Nuclear and mitochondrial DNA are thought to be of separate [[evolution]]ary origin, with the mtDNA being derived from the [[circular DNA|circular genomes]] of the [[bacteria]] that were engulfed by the early ancestors of today's eukaryotic cells. Each mitochondrion is estimated to contain 2-10 mtDNA copies.<ref name=Wiesner>{{cite journal | author=Wiesner RJ, Ruegg JC, Morano I |date=1992 |title=Counting target molecules by exponential polymerase chain reaction, copy number of mitochondrial DNA in rat tissues | journal=Biochim Biophys Acta. | volume=183 |pages=553–559 |pmid=1550563}}</ref> In the cells of extant organisms, the vast majority of the proteins present in the mitochondria (numbering approximately 1500 different types in [[mammal]]s) are coded for by nuclear DNA, but the genes for some of them, if not most, are thought to have originally been of bacterial origin, having since been transferred to the eukaryotic nucleus during [[evolution]]. In most [[metazoans|multicellular organisms]], mtDNA is inherited from the mother (maternally inherited). Mechanisms for this include simple dilution (an egg contains 100,000 to 1,000,000 mtDNA molecules, whereas a [[sperm]] contains only 100 to 1000), degradation of sperm mtDNA in the fertilized egg, and, at least in a few organisms, failure of sperm mtDNA to enter the egg. Whatever the mechanism, this single parent (uniparental) pattern of mtDNA inheritance is found in most animals, most plants and in fungi as well. mtDNA is particularly susceptible to [[reactive oxygen species]] generated by the [[respiratory chain]] due to its close proximity. Though mtDNA is packaged by proteins and harbors significant DNA repair capacity, these protective functions are less robust than those operating on nuclear DNA and therefore thought to contribute to enhanced susceptibility of mtDNA to oxidative damage. Mutations in mtDNA cause maternally inherited diseases and are thought to be a major contributor to aging and age-associated pathology.
In humans (and probably in [[metazoans]] in general), 100-10,000 separate copies of mtDNA are usually present per cell (egg and sperm cells are exceptions). In mammals, each circular mtDNA [[molecule]] consists of 15,000-17,000 [[base pair]]s, which encode the same 37 genes: 13 for proteins (polypeptides), 22 for [[transfer RNA]] (tRNA) and one each for the small and large subunits of [[ribosomal RNA]] (rRNA). This pattern is also seen among most metazoans, although in some cases one or more of the 37 genes is absent and the mtDNA size range is greater. Even greater variation in mtDNA 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). Some plant species have enormous mtDNAs (as many as 2,500,000 base pairs per mtDNA molecule) but, surprisingly, even those huge mtDNAs contain the same number and kinds of genes as related plants with much smaller mtDNAs.
==Use in identification==
Unlike nuclear DNA, which is inherited from both parents and in which genes are rearranged in the process of [[Genetic_recombination|recombination]], there is usually no change in mtDNA from parent to offspring. Although mtDNA also recombines, it does so with copies of itself within the same mitochondrion. Because of this and because the mutation rate of animal mtDNA is higher than that of nuclear DNA,<ref name=Brown>{{cite journal | author=Brown WM, George M Jr., Wilson AC |date=1979 | title=Rapid evolution of mitochondrial DNA | journal=Proc Natl Acad Sci USA | volume=76 | pages=1967–1971 |pmid=109836 | doi=10.1073/pnas.76.4.1967}}</ref> mtDNA 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. Human mtDNA can be used to identify individuals.<ref>{{cite journal | author=Brown WM |date=1980 | title=Polymorphism in mitochondrial DNA of humans as revealed by restriction endonuclease analysis | journal=Proc Natl Acad Sci USA |volume=77 | pages=3605–3609 | pmid=6251473 | doi=10.1073/pnas.77.6.3605}}</ref>
Forensic laboratories occasionally use mtDNA comparison to identify human remains, and especially to identify older unidentified skeletal remains. Although unlike nuclear DNA mtDNA is not specific to one individual, it can be used in combination with other evidence (anthropological evidence, circumstantial evidence, and the like) to establish identification. mtDNA is also used to exclude possible matches between missing persons and unidentified remains.<ref>[http://www.ancientdna.com/forensic.html Paleo-DNA Laboratory - Forensic Services<!-- Bot generated title -->]</ref> Many researchers believe that mtDNA is better suited to identification of older skeletal remains than nuclear DNA because it is often easier to harvest from older remains because of the greater number of copies of mtDNA per cell, and because a match with a living relative is possible even if numerous maternal generations separate the two. [[United States|American]] outlaw [[Jesse James]]'s remains were identified using a comparison between mtDNA extracted from his remains and the mtDNA of the son of the female-line great-granddaughter of his sister.<ref>http://www.eva.mpg.de/genetics/pdf/Stone.JFS.2001.pdf</ref>
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Because the base sequence of animal mtDNA changes rapidly, it is 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, provided they are not too distantly related. To do this, biologists determine and then compare the mtDNA 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. This approach has limits that are imposed by the rate of mtDNA sequence change. In animals, the rapid rate of change makes mtDNA most useful for comparisons of individuals within species and for comparisons of species that are closely or moderately-closely related, among which the number of sequence differences can be easily counted. As the species become more distantly related, the number of sequence differences becomes very large; changes begin to accumulate on changes until an accurate count becomes impossible.
==Mitochondrial inheritance==
===Female inheritance===
In [[Sexual reproduction|sexually reproducing organisms]], 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]].<ref>{{cite journal | author=Sutovsky, P., et. al|year=Nov. 25, 1999|title=Ubiquitin tag for sperm mitochondria|journal=[[Nature (journal)|Nature]]|volume=402|pages=371–372|pmid=10586873|doi=10.1038/46466}} Discussed in [http://www.sciencenews.org/20000101/fob3.asp].</ref> Some ''in vitro'' fertilization techniques, particularly injecting a sperm into an oocyte, may interfere with this.
The fact that mitochondrial DNA is maternally inherited enables researchers to trace [[Matrilineality|maternal lineage]] far back in time. ([[Y chromosome|Y chromosomal DNA]], paternally inherited, is used in an analogous way to trace the agnate lineage.) This is accomplished in humans by sequencing one or more of the [[hypervariable control region]]s (HVR1 or HVR2) of the mitochondrial DNA. HVR1 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. Vilà ''et al'' have published studies tracing the matrilineal descent of domestic dogs to wolves.<ref name="Vila">{{cite journal
| author = Vilà C, Savolainen P, Maldonado JE, and Amorin IR
| date = 13
| year = 1997
| month = June
| title = Multiple and Ancient Origins of the Domestic Dog
| journal = [[Science (journal)|Science]]
| volume = 276
| pages = 1687–1689
| doi = 10.1126/science.276.5319.1687
| issn = 0036-8075
| pmid = 9180076
}}</ref>
The concept of the [[Mitochondrial Eve]] is based on the same type of analysis, attempting to discover the origin of [[human]]ity by tracking the lineage back in time.
Because mtDNA is not highly conserved and has a rapid mutation rate, it is useful for studying the evolutionary relationships - [[phylogeny]] - of organisms. Biologists can determine and then compare mtDNA sequences among different species and use the comparisons to build an evolutionary tree for the species examined.
===Male inheritance===
It has been reported that mitochondria can occasionally be [[Paternal mtDNA transmission|inherited from the father]] in some species such as [[mussel]]s.<ref name="Hoeh">{{cite journal
| author = Hoeh WR, Blakley KH, Brown WM
| date = 1991
| title = Heteroplasmy suggests limited biparental inheritance of Mytilus mitochondrial DNA
| journal = Science
| volume = 251
| pages = 1488–1490
| pmid = 1672472
| doi = 10.1126/science.1672472
}}</ref><ref name="Penman">{{cite news
| first = Danny
| last = Penman
| url = http://www.newscientist.com/article.ns?id=dn2716
| title = Mitochondria can be inherited from both parents
| work = NewScientist.com
| date = [[23 August]] [[2002]]
| accessdate = 2008-02-05
}}</ref>
Paternally inherited mitochondria have also been reported in some insects such as the fruit fly<ref>{{cite journal |author=Kondo R, Matsuura ET, Chigusa SI |title=Further observation of paternal transmission of Drosophila mitochondrial DNA by PCR selective amplification method |journal=Genet. Res. |volume=59 |issue=2 |pages=81–4 |year=1992 |pmid=1628820}}</ref> and the honeybee.<ref>{{cite journal |author=Meusel MS, Moritz RF |title=Transfer of paternal mitochondrial DNA during fertilization of honeybee (Apis mellifera L.) eggs |journal=Curr. Genet. |volume=24 |issue=6 |pages=539–43 |year=1993 |pmid=8299176 |doi=10.1007/BF00351719}}</ref>
Evidence supports rare instances of male mitochondrial inheritance in some mammals as well. Specifically, documented occurrences exist for mice,<ref>{{cite journal |author=Gyllensten U, Wharton D, Josefsson A, Wilson AC |title=Paternal inheritance of mitochondrial DNA in mice |journal=Nature |volume=352 |issue=6332 |pages=255–7 |year=1991 |pmid=1857422 |doi=10.1038/352255a0}}</ref><ref>{{cite journal |author=Shitara H, Hayashi JI, Takahama S, Kaneda H, Yonekawa H |title=Maternal inheritance of mouse mtDNA in interspecific hybrids: segregation of the leaked paternal mtDNA followed by the prevention of subsequent paternal leakage |journal=Genetics |volume=148 |issue=2 |pages=851–7 |year=1998 |pmid=9504930}}</ref> where the male-inherited mitochondria was subsequently rejected. It has also been found in sheep,<ref>{{cite journal |author=Zhao X, Li N, Guo W, ''et al'' |title=Further evidence for paternal inheritance of mitochondrial DNA in the sheep (Ovis aries) |journal=Heredity |volume=93 |issue=4 |pages=399–403 |year=2004 |pmid=15266295 |doi=10.1038/sj.hdy.6800516}}</ref> and in cloned cattle.<ref>{{cite journal |author=Steinborn R, Zakhartchenko V, Jelyazkov J, ''et al'' |title=Composition of parental mitochondrial DNA in cloned bovine embryos |journal=FEBS Lett. |volume=426 |issue=3 |pages=352–6 |year=1998 |pmid=9600265 |doi=10.1016/S0014-5793(98)00350-0}}</ref> It has been found in a single case in a human male and was linked to infertility.<ref>{{cite journal |author=Schwartz M, Vissing J |title=Paternal inheritance of mitochondrial DNA |journal=N. Engl. J. Med. |volume=347 |issue=8 |pages=576–80 |year=2002 |pmid=12192017 |doi=10.1056/NEJMoa020350}}</ref>
While many of these cases involve cloned embryos or subsequent rejection of the paternal mitochondria, others document ''in vivo'' inheritance and persistence under lab conditions.
==Genes==
* [[ATP synthase]]: {{Gene|MT-ATP6}}, {{Gene|MT-ATP8}}
* [[cytochrome c oxidase]]: {{Gene|MT-CO1}}, {{Gene|MT-CO2}}, {{Gene|MT-CO3}}, {{Gene|MT-CYB}}
* [[NADH dehydrogenase]]: [[MT-ND1]], {{Gene|MT-ND2}}, {{Gene|MT-ND3}}, {{Gene|MT-ND4}}, {{Gene|MT-ND4L}}, [[MT-ND5]], {{Gene|MT-ND6}}
* 12S, 16S: {{Gene|MT-RNR1}}, {{Gene|MT-RNR2}}
* [[tRNA]]: {{Gene|MT-TA}}, {{Gene|MT-TC}}, {{Gene|MT-TD}}, {{Gene|MT-TE}}, {{Gene|MT-TF}}, {{Gene|MT-TG}}, [[MT-TH]], {{Gene|MT-TI}}, {{Gene|MT-TK}}, [[MT-TL1]], {{Gene|MT-TL2}}, {{Gene|MT-TM}}, {{Gene|MT-TN}}, {{Gene|MT-TP}}, {{Gene|MT-TQ}}, {{Gene|MT-TR}}, {{Gene|MT-TS1}}, {{Gene|MT-TS2}}, {{Gene|MT-TT}}, {{Gene|MT-TV}}, {{Gene|MT-TW}}, {{Gene|MT-TY}}, {{Gene|MT1X}}
==Genetic influence==
===Genetic illness===
Mutations of mitochondrial DNA can lead to a number of illnesses including [[exercise intolerance]] and [[Kearns-Sayre syndrome]] (KSS), which causes a person to lose full function of their heart, eye, and muscle movements.
(See also [[Mitochondrial disease]]).
==See also==
* [[Mitochondrial disease]]
* [[Human mitochondrial genetics]]
* [[Paternal mtDNA transmission]]
* [[Single origin theory]]
* [[Mitochondrial Eve]]
* [[Cambridge Reference Sequence|Mitochondrial CRS]]
==References==
{{Reflist|2}}
==External links==
* Mitomap - a human mitochondrial genome database [http://www.mitomap.org/]
* [http://www.ianlogan.co.uk/mtDNA.htm Defining mutations of mtDNA haplogroups and subclades]
* [http://www.mitosearch.org/ MitoSearch : public mtDNA database]
* [http://medicina.xenomica.org/en/mtdna/mtdna_10.html mtDNA mutation rates]
* [http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6W4M-45RF6M8-2&_coverDate=08%2F31%2F1995&_alid=284977920&_rdoc=1&_fmt=&_orig=search&_qd=1&_cdi=6546&_sort=d&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=8bd4188e19f98026ee147e31d445f4f9 A polymorphism in mitochondrial DNA associated with IQ?]
* [http://www.bradshawfoundation.com/stephenoppenheimer mtDNA and the global diaspora of modern humans] Professor Stephen Oppenheimer's Genetic Map
* [http://www.empop.org/ EMPOP - Mitochondrial DNA Control Region Database]
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{{Mitochondrial DNA}}
[[Category:DNA]]
[[Category: Mitochondrial genetics]]
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