Mitochondrial DNA - AbsoluteAstronomy.com

Mitochondrial DNA is the DNA

DNA

Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...

located in organelles called mitochondria

Mitochondrion

In cell biology, a mitochondrion is a membrane-enclosed organelle found in most eukaryotic cells. These organelles range from 0.5 to 1.0 micrometers in diameter...

, structures within eukaryotic cells that convert the chemical energy from food into a form that cells can use, adenosine triphosphate

Adenosine triphosphate

Adenosine-5'-triphosphate is a multifunctional nucleoside triphosphate used in cells as a coenzyme. It is often called the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...

(ATP). Most other DNA present in eukaryotic organisms is found in the cell nucleus

Cell nucleus

In cell biology, the nucleus is a membrane-enclosed organelle found in eukaryotic cells. It contains most of the cell's genetic material, organized as multiple long linear DNA molecules in complex with a large variety of proteins, such as histones, to form chromosomes. The genes within these...

.

Mitochondrial DNA can be regarded as the smallest chromosome

Chromosome

A chromosome is an organized structure of DNA and protein found in cells. It is a single piece of coiled DNA containing many genes, regulatory elements and other nucleotide sequences. Chromosomes also contain DNA-bound proteins, which serve to package the DNA and control its functions.Chromosomes...

, and was the first significant part of the human genome

Human genome

The human genome is the genome of Homo sapiens, which is stored on 23 chromosome pairs plus the small mitochondrial DNA. 22 of the 23 chromosomes are autosomal chromosome pairs, while the remaining pair is sex-determining...

to be sequenced. In most species, including humans, mtDNA is inherited solely from the mother.

The DNA sequence of mtDNA has been determined from a large number of organisms and individuals (including some organisms that are extinct), and the comparison of those DNA sequences represents a mainstay of phylogenetics

Phylogenetics

In biology, phylogenetics is the study of evolutionary relatedness among groups of organisms , which is discovered through molecular sequencing data and morphological data matrices...

, in that it allows biologists to elucidate the evolutionary relationships among species. It also permits an examination of the relatedness of populations, and so has become important in anthropology

Anthropology

Anthropology is the study of humanity. It has origins in the humanities, the natural sciences, and the social sciences. The term "anthropology" is from the Greek anthrōpos , "man", understood to mean mankind or humanity, and -logia , "discourse" or "study", and was first used in 1501 by German...

and field biology.

Replication

mtDNA is replicated by the DNA polymerase

DNA polymerase

A DNA polymerase is an enzyme that helps catalyze in the polymerization of deoxyribonucleotides into a DNA strand. DNA polymerases are best known for their feedback role in DNA replication, in which the polymerase "reads" an intact DNA strand as a template and uses it to synthesize the new strand....

gamma complex which is composed of a 140 kDa catalytic DNA polymerase encoded by the POLG
POLG
DNA polymerase subunit gamma is an enzyme that in humans is encoded by the POLG gene.-Functions:POLG is the gene that codes for the catalytic subunit of the mitochondrial DNA polymerase, called DNA polymerase gamma . The human POLG cDNA and gene were originally cloned mapped to chromosome 15,...

gene and a 55 kDa accessory subunit encoded by the POLG2
POLG2
DNA polymerase subunit gamma-2, mitochondrial is an protein that in humans is encoded by the POLG2 gene. The POLG2 gene encodes a 55 kDa accessory subunit protein that imparts high processivity and salt tolerance to the catalytic subunit of DNA polymerase gamma, encoded by the POLG gene. -Further...

gene. During embryogenesis

Embryogenesis

Embryogenesis is the process by which the embryo is formed and develops, until it develops into a fetus.Embryogenesis starts with the fertilization of the ovum by sperm. The fertilized ovum is referred to as a zygote...

, replication of mtDNA is strictly down-regulated from the fertilized oocyte through the preimplantation embryo. At the blastocyst

Blastocyst

The blastocyst is a structure formed in the early embryogenesis of mammals, after the formation of the morula. It is a specifically mammalian example of a blastula. It possesses an inner cell mass , or embryoblast, which subsequently forms the embryo, and an outer layer of cells, or trophoblast,...

stage, the onset of mtDNA replication is specific to the cells of the trophectoderm. In contrast, the cells of the inner cell mass

Inner cell mass

In early embryogenesis of most eutherian mammals, the inner cell mass is the mass of cells inside the primordial embryo that will eventually give rise to the definitive structures of the fetus...

restrict mtDNA replication until they receive the signals

Cell signaling

Cell signaling is part of a complex system of communication that governs basic cellular activities and coordinates cell actions. The ability of cells to perceive and correctly respond to their microenvironment is the basis of development, tissue repair, and immunity as well as normal tissue...

to differentiate

Cellular differentiation

In developmental biology, cellular differentiation is the process by which a less specialized cell becomes a more specialized cell type. Differentiation occurs numerous times during the development of a multicellular organism as the organism changes from a simple zygote to a complex system of...

to specific cell types.

Origin

Nuclear and mitochondrial DNA are thought to be of separate evolution

Evolution

Evolution is any change across successive generations in the heritable characteristics of biological populations. Evolutionary processes give rise to diversity at every level of biological organisation, including species, individual organisms and molecules such as DNA and proteins.Life on Earth...

ary origin, with the mtDNA being derived from the circular genomes

Circular DNA

Circular DNA is a form of DNA that is found in viruses, bacteria and archaea as well as in eukaryotic cells in the form of either mitochondrial DNA or plastid DNA....

of the bacteria

Bacteria

Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...

that were engulfed by the early ancestors of today's eukaryotic cells. This theory is called the endosymbiotic theory

Endosymbiotic theory

The endosymbiotic theory concerns the mitochondria, plastids , and possibly other organelles of eukaryotic cells. According to this theory, certain organelles originated as free-living bacteria that were taken inside another cell as endosymbionts...

. Each mitochondrion is estimated to contain 2-10 mtDNA copies. In the cells of extant organisms, the vast majority of the proteins present in the mitochondria (numbering approximately 1500 different types in mammal

Mammal

Mammals are members of a class of air-breathing vertebrate animals characterised by the possession of endothermy, hair, three middle ear bones, and mammary glands functional in mothers with young...

s) are coded for by nuclear DNA

Nuclear DNA

Nuclear DNA, nuclear deoxyribonucleic acid , is DNA contained within a nucleus of eukaryotic organisms. In mammals and vertebrates, nuclear DNA encodes more of the genome than the mitochondrial DNA and is composed of information inherited from two parents, one male, and one female, rather than...

, 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

Evolution

Mitochondrial inheritance

In most 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

Sperm

The term sperm is derived from the Greek word sperma and refers to the male reproductive cells. In the types of sexual reproduction known as anisogamy and oogamy, there is a marked difference in the size of the gametes with the smaller one being termed the "male" or sperm cell...

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.

Female inheritance

In sexual reproduction

Sexual reproduction

Sexual reproduction is the creation of a new organism by combining the genetic material of two organisms. There are two main processes during sexual reproduction; they are: meiosis, involving the halving of the number of chromosomes; and fertilization, involving the fusion of two gametes and the...

, 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

Ubiquitin

Ubiquitin is a small regulatory protein that has been found in almost all tissues of eukaryotic organisms. Among other functions, it directs protein recycling.Ubiquitin can be attached to proteins and label them for destruction...

to select them for later destruction inside the embryo

Embryo

An embryo is a multicellular diploid eukaryote in its earliest stage of development, from the time of first cell division until birth, hatching, or germination...

. Some in vitro
In vitro
In vitro refers to studies in experimental biology that are conducted using components of an organism that have been isolated from their usual biological context in order to permit a more detailed or more convenient analysis than can be done with whole organisms. Colloquially, these experiments...

fertilization techniques, particularly injecting a sperm into an oocyte

Oocyte

An oocyte, ovocyte, or rarely ocyte, is a female gametocyte or germ cell involved in reproduction. In other words, it is an immature ovum, or egg cell. An oocyte is produced in the ovary during female gametogenesis. The female germ cells produce a primordial germ cell which undergoes a mitotic...

, may interfere with this.

The fact that mitochondrial DNA is maternally inherited enables researchers to trace maternal lineage

Matrilineality

Matrilineality is a system in which descent is traced through the mother and maternal ancestors. Matrilineality is also a societal system in which one belongs to one's matriline or mother's lineage, which can involve the inheritance of property and/or titles.A matriline is a line of descent from a...

far back in time. ( Y-chromosomal DNA

Y chromosome

The Y chromosome is one of the two sex-determining chromosomes in most mammals, including humans. In mammals, it contains the gene SRY, which triggers testis development if present. The human Y chromosome is composed of about 60 million base pairs...

, 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 regions (HVR1 or HVR2) of the mitochondrial DNA, as with a genealogical DNA test

Genealogical DNA test

A genealogical DNA test examines the nucleotides at specific locations on a person's DNA for genetic genealogy purposes. The test results are not meant to have any informative medical value and do not determine specific genetic diseases or disorders ; they are intended only to give genealogical...

. 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 Cambridge Reference Sequence

Cambridge Reference Sequence

The Cambridge Reference Sequence for human mitochondrial DNA was first published in 1981 leading to the initiation of the human genome project.A group under Dr...

. Vilà et al. have published studies tracing the matrilineal descent of domestic dogs to wolves.
The concept of the Mitochondrial Eve

Mitochondrial Eve

In the field of human genetics, Mitochondrial Eve refers to the matrilineal "MRCA" . In other words, she was the woman from whom all living humans today descend, on their mother's side, and through the mothers of those mothers and so on, back until all lines converge on one person...

is based on the same type of analysis, attempting to discover the origin of human

Human

Humans are the only living species in the Homo genus...

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.

Because mtDNA is transmitted from mother to child (both male and female), it can be a useful tool in genealogical

Genetic genealogy

Genetic genealogy is the application of genetics to traditional genealogy. Genetic genealogy involves the use of genealogical DNA testing to determine the level of genetic relationship between individuals.-History:...

research into a person's maternal line.

Male inheritance

It has been reported that mitochondria can occasionally be inherited from the father

Paternal mtDNA transmission

In genetics, paternal mtDNA transmission and paternal mtDNA inheritance refer to the incidence of mitochondrial DNA being passed from a father to his offspring. Paternal mtDNA inheritance is observed in a small proportion of species; in general, mtDNA is passed unchanged from a mother to her...

in some species such as mussel

Mussel

The common name mussel is used for members of several families of clams or bivalvia mollusca, from saltwater and freshwater habitats. These groups have in common a shell whose outline is elongated and asymmetrical compared with other edible clams, which are often more or less rounded or oval.The...

s.
Paternally inherited mitochondria have additionally been reported in some insects such as fruit flies, honeybees, and periodical cicadas

Magicicada

Magicicada is the genus of the 13- and 17-year periodical cicadas of eastern North America. They are sometimes called "17-year locusts", although cicadas belong to order Hemiptera, while locusts are Orthoptera....

.

Evidence supports rare instances of male mitochondrial inheritance in some mammals as well. Specifically, documented occurrences exist for mice, where the male-inherited mitochondria was subsequently rejected. It has also been found in sheep, and in cloned cattle. It has been found in a single case in a human male.

While many of these cases involve cloned embryos or subsequent rejection of the paternal mitochondria, others document in vivo
In vivo
In vivo is experimentation using a whole, living organism as opposed to a partial or dead organism, or an in vitro controlled environment. Animal testing and clinical trials are two forms of in vivo research...

inheritance and persistence under lab conditions.

Structure

In humans (and probably in metazoans in general), 100-10,000 separate copies of mtDNA are usually present per cell (egg and sperm cells

Spermatozoon

A spermatozoon is a motile sperm cell, or moving form of the haploid cell that is the male gamete. A spermatozoon joins an ovum to form a zygote...

are exceptions). In mammals, each double-stranded circular mtDNA molecule

Molecule

A molecule is an electrically neutral group of at least two atoms held together by covalent chemical bonds. Molecules are distinguished from ions by their electrical charge...

consists of 15,000-17,000 base pair

Base pair

In molecular biology and genetics, the linking between two nitrogenous bases on opposite complementary DNA or certain types of RNA strands that are connected via hydrogen bonds is called a base pair...

s. The two strands of mtDNA are differentiated by their nucleotide content with the guanine rich strand referred to as the heavy strand, and the cytosine rich strand referred to as the light strand. The heavy strand encodes 28 genes, and the light strand encodes 9 genes for a total of 37 genes. Of the 37 genes, 13 are for proteins (polypeptides), 22 are for transfer RNA

Transfer RNA

Transfer RNA is an adaptor molecule composed of RNA, typically 73 to 93 nucleotides in length, that is used in biology to bridge the three-letter genetic code in messenger RNA with the twenty-letter code of amino acids in proteins. The role of tRNA as an adaptor is best understood by...

(tRNA) and two are for the small and large subunits of ribosomal RNA

Ribosomal RNA

Ribosomal ribonucleic acid is the RNA component of the ribosome, the enzyme that is the site of protein synthesis in all living cells. Ribosomal RNA provides a mechanism for decoding mRNA into amino acids and interacts with tRNAs during translation by providing peptidyl transferase activity...

(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.

The genome of the mitochondrion of the cucumber (Cucumis sativus) is three entirely or largely autonomous circular chromosomes (lengths 1556, 84 and 45 kilobases).

Genes

Note: The gene content of mitochondrial DNA varies among species. Information in this section is specific to human mitochondrial DNA

Electron transport chain

The mitochondrial genome contains 13 protein-coding genes. Many of these genes encode proteins of the electron transport chain:

Category	Genes
NADH dehydrogenase NADH dehydrogenase NADH dehydrogenase is an enzyme located in the inner mitochondrial membrane that catalyzes the transfer of electrons from NADH to coenzyme Q... (complex I)	MT-ND1 MT-ND1 MT-ND1 is a mitochondrial gene. It is associated with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes.-External links:... , MT-ND2, MT-ND3, MT-ND4, MT-ND4L, MT-ND5 MT-ND5 MT-ND5 is a mitochondrial gene. It is associated with MELAS or mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes.-External links:... , MT-ND6
Coenzyme Q - cytochrome c reductase Coenzyme Q - cytochrome c reductase In enzymology, a ubiquinol—cytochrome-c reductase is an enzyme that catalyzes the chemical reactionThus, the two substrates of this enzyme are dihydroquinone and ferri- cytochrome c, whereas its 3 products are quinone , ferro- cytochrome c, and H+.This enzyme belongs to the family of... /Cytochrome b Cytochrome b Cytochrome b/b6 is the main subunit of transmembrane cytochrome bc1 and b6f complexes. In addition, it commonly refers to a region of mtDNA used for population genetics and phylogenetics.- Function :... (complex III)	MT-CYB
cytochrome c oxidase Cytochrome c oxidase The enzyme cytochrome c oxidase or Complex IV is a large transmembrane protein complex found in bacteria and the mitochondrion.It is the last enzyme in the respiratory electron transport chain of mitochondria located in the mitochondrial membrane... (complex IV)	MT-CO1, MT-CO2, MT-CO3
ATP synthase ATP synthase right\|thumb\|300px\|Molecular model of ATP synthase by X-ray diffraction methodATP synthase is an important enzyme that provides energy for the cell to use through the synthesis of adenosine triphosphate . ATP is the most commonly used "energy currency" of cells from most organisms...	MT-ATP6, MT-ATP8

tRNA

The following genes encode tRNA:

Amino Acid	3-Letter	1-Letter	MT DNA
Alanine Alanine Alanine is an α-amino acid with the chemical formula CH3CHCOOH. The L-isomer is one of the 20 amino acids encoded by the genetic code. Its codons are GCU, GCC, GCA, and GCG. It is classified as a nonpolar amino acid...	Ala	A	MT-TA MT-TA Mitochondrially encoded tRNA alanine also known as MT-TA is a transfer RNA, which in humans is encoded by the mitochondrial MT-TA gene....
Arginine Arginine Arginine is an α-amino acid. The L-form is one of the 20 most common natural amino acids. At the level of molecular genetics, in the structure of the messenger ribonucleic acid mRNA, CGU, CGC, CGA, CGG, AGA, and AGG, are the triplets of nucleotide bases or codons that codify for arginine during...	Arg	R	MT-TR MT-TR Mitochondrially encoded tRNA arginine also known as MT-TR is a transfer RNA which in humans is encoded by the mitochondrial MT-TR gene....
Asparagine Asparagine Asparagine is one of the 20 most common natural amino acids on Earth. It has carboxamide as the side-chain's functional group. It is not an essential amino acid...	Asn	N	MT-TN MT-TN Mitochondrially encoded tRNA asparagine also known as MT-TN is a transfer RNA which in humans is encoded by the mitochondrial MT-TN gene....
Aspartic acid Aspartic acid Aspartic acid is an α-amino acid with the chemical formula HOOCCHCH2COOH. The carboxylate anion, salt, or ester of aspartic acid is known as aspartate. The L-isomer of aspartate is one of the 20 proteinogenic amino acids, i.e., the building blocks of proteins...	Asp	D	MT-TD MT-TD Mitochondrially encoded tRNA aspartic acid also known as MT-TD is a transfer RNA which in humans is encoded by the mitochondrial MT-TD gene....
Cysteine Cysteine Cysteine is an α-amino acid with the chemical formula HO2CCHCH2SH. It is a non-essential amino acid, which means that it is biosynthesized in humans. Its codons are UGU and UGC. The side chain on cysteine is thiol, which is polar and thus cysteine is usually classified as a hydrophilic amino acid...	Cys	C	MT-TC MT-TC Mitochondrially encoded tRNA cysteine also known as MT-TC is a transfer RNA which in humans is encoded by the mitochondrial MT-TC gene....
Glutamic acid Glutamic acid Glutamic acid is one of the 20 proteinogenic amino acids, and its codons are GAA and GAG. It is a non-essential amino acid. The carboxylate anions and salts of glutamic acid are known as glutamates...	Glu	E	MT-TE MT-TE Mitochondrially encoded tRNA glutamic acid also known as MT-TE is a transfer RNA which in humans is encoded by the mitochondrial MT-TE gene....
Glutamine Glutamine Glutamine is one of the 20 amino acids encoded by the standard genetic code. It is not recognized as an essential amino acid but may become conditionally essential in certain situations, including intensive athletic training or certain gastrointestinal disorders...	Gln	Q	MT-TQ MT-TQ Mitochondrially encoded tRNA glutamine also known as MT-TQ is a transfer RNA which in humans is encoded by the mitochondrial MT-TQ gene....
Glycine Glycine Glycine is an organic compound with the formula NH2CH2COOH. Having a hydrogen substituent as its 'side chain', glycine is the smallest of the 20 amino acids commonly found in proteins. Its codons are GGU, GGC, GGA, GGG cf. the genetic code.Glycine is a colourless, sweet-tasting crystalline solid...	Gly	G	MT-TG MT-TG Mitochondrially encoded tRNA glycine also known as MT-TG is a transfer RNA which in humans is encoded by the mitochondrial MT-TG gene....
Histidine Histidine Histidine Histidine, an essential amino acid, has a positively charged imidazole functional group. It is one of the 22 proteinogenic amino acids. Its codons are CAU and CAC. Histidine was first isolated by German physician Albrecht Kossel in 1896. Histidine is an essential amino acid in humans...	His	H	MT-TH MT-TH Mitochondrially encoded tRNA histidine, also known as MT-TH, is a transfer RNA which, in humans, is encoded by the mitochondrial MT-TH gene.-Function:...
Isoleucine Isoleucine Isoleucine is an α-amino acid with the chemical formula HO2CCHCHCH2CH3. It is an essential amino acid, which means that humans cannot synthesize it, so it must be ingested. Its codons are AUU, AUC and AUA....	Ile	I	MT-TI MT-TI Mitochondrially encoded tRNA isoleucine also known as MT-TI is a transfer RNA which in humans is encoded by the mitochondrial MT-TI gene....
Leucine Leucine Leucine is a branched-chain α-amino acid with the chemical formula HO2CCHCH2CH2. Leucine is classified as a hydrophobic amino acid due to its aliphatic isobutyl side chain. It is encoded by six codons and is a major component of the subunits in ferritin, astacin and other 'buffer' proteins...	Leu	L	MT-TL1 MT-TL1 Mitochondrially encoded tRNA leucine 1 also known as MT-TL1 is a transfer RNA which in humans is encoded by the mitochondrial MT-TL1 gene.-Function:... , MT-TL2 MT-TL2 Mitochondrially encoded tRNA leucine 2 also known as MT-TL2 is a transfer RNA which in humans is encoded by the mitochondrial MT-TL2 gene....
Lysine Lysine Lysine is an α-amino acid with the chemical formula HO2CCH4NH2. It is an essential amino acid, which means that the human body cannot synthesize it. Its codons are AAA and AAG....	Lys	K	MT-TK MT-TK Mitochondrially encoded tRNA lysine also known as MT-TK is a transfer RNA which in humans is encoded by the mitochondrial MT-TK gene.- Function :...
Methionine Methionine Methionine is an α-amino acid with the chemical formula HO2CCHCH2CH2SCH3. This essential amino acid is classified as nonpolar. This amino-acid is coded by the codon AUG, also known as the initiation codon, since it indicates mRNA's coding region where translation into protein...	Met	M	MT-TM MT-TM Mitochondrially encoded tRNA methionine also known as MT-TM is a transfer RNA which in humans is encoded by the mitochondrial MT-TM gene....
Phenylalanine Phenylalanine Phenylalanine is an α-amino acid with the formula C6H5CH2CHCOOH. This essential amino acid is classified as nonpolar because of the hydrophobic nature of the benzyl side chain. L-Phenylalanine is an electrically neutral amino acid, one of the twenty common amino acids used to biochemically form...	Phe	F	MT-TF MT-TF Mitochondrially encoded tRNA phenylalanine also known as MT-TF is a transfer RNA which in humans is encoded by the mitochondrial MT-TF gene....
Proline Proline Proline is an α-amino acid, one of the twenty DNA-encoded amino acids. Its codons are CCU, CCC, CCA, and CCG. It is not an essential amino acid, which means that the human body can synthesize it. It is unique among the 20 protein-forming amino acids in that the α-amino group is secondary...	Pro	P	MT-TP MT-TP Mitochondrially encoded tRNA proline also known as MT-TP is a transfer RNA which in humans is encoded by the mitochondrial MT-TP gene....
Serine Serine Serine is an amino acid with the formula HO2CCHCH2OH. It is one of the proteinogenic amino acids. By virtue of the hydroxyl group, serine is classified as a polar amino acid.-Occurrence and biosynthesis:...	Ser	S	MT-TS1 MT-TS1 Mitochondrially encoded tRNA serine 1 also known as MT-TS1 is a transfer RNA which in humans is encoded by the mitochondrial MT-TS1 gene.... , MT-TS2 MT-TS2 Mitochondrially encoded tRNA serine 2 also known as MT-TS2 is a transfer RNA which in humans is encoded by the mitochondrial MT-TS2 gene....
Threonine Threonine Threonine is an α-amino acid with the chemical formula HO2CCHCHCH3. Its codons are ACU, ACA, ACC, and ACG. This essential amino acid is classified as polar...	Thr	T	MT-TT MT-TT Mitochondrially encoded tRNA threonine also known as MT-TT is a transfer RNA which in humans is encoded by the mitochondrial MT-TT gene....
Tryptophan Tryptophan Tryptophan is one of the 20 standard amino acids, as well as an essential amino acid in the human diet. It is encoded in the standard genetic code as the codon UGG...	Trp	W	MT-TW MT-TW Mitochondrially encoded tRNA tryptophan also known as MT-TW is a transfer RNA which in humans is encoded by the mitochondrial MT-TW gene....
Tyrosine Tyrosine Tyrosine or 4-hydroxyphenylalanine, is one of the 22 amino acids that are used by cells to synthesize proteins. Its codons are UAC and UAU. It is a non-essential amino acid with a polar side group...	Tyr	Y	MT-TY MT-TY Mitochondrially encoded tRNA tyrosine also known as MT-TY is a transfer RNA which in humans is encoded by the mitochondrial MT-TY gene....
Valine Valine Valine is an α-amino acid with the chemical formula HO2CCHCH2. L-Valine is one of 20 proteinogenic amino acids. Its codons are GUU, GUC, GUA, and GUG. This essential amino acid is classified as nonpolar...	Val	V	MT-TV MT-TV (mitochondrial) Mitochondrially encoded tRNA valine also known as MT-TV is a transfer RNA which in humans is encoded by the mitochondrial MT-TV gene....

Mutations

Susceptibility

mtDNA is particularly susceptible to reactive oxygen species

Reactive oxygen species

Reactive oxygen species are chemically reactive molecules containing oxygen. Examples include oxygen ions and peroxides. Reactive oxygen species are highly reactive due to the presence of unpaired valence shell electrons....

generated by the respiratory chain due to its proximity. Though mtDNA is packaged by proteins and harbors significant DNA repair

DNA repair

DNA repair refers to a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as UV light and radiation can cause DNA damage, resulting in as many as 1...

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. The outcome of mutation in mtDNA may be alteration in the coding instructions for some proteins, which may have an effect on organism metabolism and/or fitness.

Genetic illness

Mutations of mitochondrial DNA can lead to a number of illnesses including exercise intolerance

Exercise intolerance

Exercise intolerance is a condition where the patient is unable to do physical exercise at the level or for the duration that would be expected of someone in his or her general physical condition, or experiences unusually severe post-exercise pain, fatigue, or other negative effects...

and Kearns-Sayre syndrome

Kearns-Sayre syndrome

Kearns–Sayre syndrome also known as oculocraniosomatic disease or Oculocraniosomatic neuromuscular disease with ragged red fibers is a mitochondrial myopathy with a typical onset before 20 years of age...

(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.

Use in Disease Diagnosis

Recently a mutation in mtDNA has been used to help diagnose prostate cancer in patients with negative prostate biopsy

Prostate biopsy

Prostate biopsy is a procedure in which small samples are removed from a man's prostate gland to be tested for the presence of cancer. It is typically performed when the scores from a PSA blood test rise to a level that is associated with the possible presence of prostate cancer.The procedure,...

Use in identification

In humans, mitochondrial DNA spans 16,569 DNA building blocks (base pairs), representing a fraction of the total DNA in cells. Unlike nuclear DNA, which is inherited from both parents and in which genes are rearranged in the process of recombination

Genetic recombination

Genetic recombination is a process by which a molecule of nucleic acid is broken and then joined to a different one. Recombination can occur between similar molecules of DNA, as in homologous recombination, or dissimilar molecules, as in non-homologous end joining. Recombination is a common method...

, 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

Mutation rate

In genetics, the mutation rate is the chance of a mutation occurring in an organism or gene in each generation...

of animal mtDNA is higher than that of nuclear DNA, 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 also be used to help identify individuals. 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

Circumstantial evidence

Circumstantial evidence is evidence in which an inference is required to connect it to a conclusion of fact, like a fingerprint at the scene of a crime...

, and the like) to establish identification. mtDNA is also used to exclude possible matches between missing person

Missing person

A missing person is a person who has disappeared for usually unknown reasons.Missing persons' photographs may be posted on bulletin boards, milk cartons, postcards, and websites, along with a phone number to be contacted if a sighting has been made....

s and unidentified remains. Many researchers believe that mtDNA is better suited to identification of older skeletal remains than nuclear DNA because the greater number of copies of mtDNA per cell increases the chance of obtaining a useful sample, and because a match with a living relative is possible even if numerous maternal generations separate the two. American

United States

The United States of America is a federal constitutional republic comprising fifty states and a federal district...

outlaw Jesse James

Jesse James

Jesse Woodson James was an American outlaw, gang leader, bank robber, train robber, and murderer from the state of Missouri and the most famous member of the James-Younger Gang. He also faked his own death and was known as J.M James. Already a celebrity when he was alive, he became a legendary...

'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. Similarly, the remains of Alexandra Feodorovna (Alix of Hesse), last Empress of Russia, and her children were identified by comparison of their mitochondrial DNA with that of Prince Philip, Duke of Edinburgh

Prince Philip, Duke of Edinburgh

Prince Philip, Duke of Edinburgh is the husband of Elizabeth II. He is the United Kingdom's longest-serving consort and the oldest serving spouse of a reigning British monarch....

, whose maternal grandmother was Alexandra’s sister Victoria of Hesse

Princess Victoria of Hesse and by Rhine

Princess Victoria of Hesse and by Rhine, later Victoria Mountbatten, Marchioness of Milford Haven was the eldest daughter of Louis IV, Grand Duke of Hesse and by Rhine and his first wife Princess Alice of the United Kingdom .Her mother died while her brother and sisters...

. Similarly to identify Emperor Nicholas II

Nicholas II of Russia

Nicholas II was the last Emperor of Russia, Grand Prince of Finland, and titular King of Poland. His official short title was Nicholas II, Emperor and Autocrat of All the Russias and he is known as Saint Nicholas the Passion-Bearer by the Russian Orthodox Church.Nicholas II ruled from 1894 until...

remains his mitochondrial DNA was compared with that of James Carnegie, 3rd Duke of Fife

James Carnegie, 3rd Duke of Fife

James George Alexander Bannerman Carnegie, 3rd Duke of Fife is a great grandson of King Edward VII of the United Kingdom and a member of the extended British Royal Family, in the line of succession to the British Throne...

, whose maternal great-grandmother Alexandra of Denmark

Alexandra of Denmark

Alexandra of Denmark was the wife of Edward VII of the United Kingdom...

(Queen Alexandra) was sister of Nicholas II mother Dagmar of Denmark (Empress Maria Feodorovna).

The low effective population size

Effective population size

In population genetics, the concept of effective population size Ne was introduced by the American geneticist Sewall Wright, who wrote two landmark papers on it...

and rapid mutation rate (in animals) makes mtDNA useful for assessing genetic relationships of individuals or groups within a species and also for identifying and quantifying the phylogeny (evolutionary relationships; see phylogenetics

Phylogenetics

In biology, phylogenetics is the study of evolutionary relatedness among groups of organisms , which is discovered through molecular sequencing data and morphological data matrices...

) 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 high mutation rate

Mutation rate

In genetics, the mutation rate is the chance of a mutation occurring in an organism or gene in each generation...

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.

History

Mitochondrial DNA was discovered in the 1960s by Margit M. K. Nass and Sylvan Nass by electron microscopy

Electron microscope

An electron microscope is a type of microscope that uses a beam of electrons to illuminate the specimen and produce a magnified image. Electron microscopes have a greater resolving power than a light-powered optical microscope, because electrons have wavelengths about 100,000 times shorter than...

as DNase-sensitive thread inside mitochondria, and by Ellen Haslbrunner, Hans Tuppy

Hans Tuppy

Hans Tuppy is a biochemist who participated in the sequencing of insulin, and became Austria's first university professor for biochemistry. He was Austrian Minister for Science and Research from 1987−1989.- Family background and youth :...

and Gottfried Schatz

Gottfried Schatz

Gottfried Schatz is a Swiss - Austrian biochemist. He played a leading role in elucidating the biogenesis of mitochondria and was a co-discoverer of mitochondrial DNA.- Life and career :...

by biochemical assays on highly purified mitochondrial fractions.