Mitochondrial DNA (mtDNA or mDNA) is the 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 is only a small portion of the DNA in a eukaryotic cell; most of the DNA can be found in the cell nucleus and, in plants and algae, also in plastids such as chloroplasts.
Since animal mtDNA evolves faster than nuclear genetic markers, 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.
Nuclear and mitochondrial DNA are thought to be of separate evolutionary origin, with the mtDNA 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. 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.
The reasons why mitochondria have retained some genes are debated. The existence in some species of mitochondrion-derived organelles lacking a genome suggests that complete gene loss is possible, and transferring mitochondrial genes to the nucleus has several advantages. The difficulty of targeting remotely-produced hydrophobic protein products to the mitochondrion is one hypothesis for why some genes are retained in mtDNA; colocalisation for redox regulation is another, citing the desirability of localised control over mitochondrial machinery. Recent analysis of a wide range of mtDNA genomes suggests that both these features may dictate mitochondrial gene retention.
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.
In many unicellular organisms (e.g., the ciliate Tetrahymena and the green alga Chlamydomonas reinhardtii), and in rare cases also in multicellular organisms (e.g. in some species of Cnidaria), the mtDNA 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 because many of these unicellular organisms with linear mtDNA are known pathogens.
There is only one mitochondrial genome type found in animal cells. This genome usually contains one circular molecule with between 11–28 kbp of genetic material (type 1).
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 to 1000 kbp in length. The second genome type is a circular genome (about 20–1000 kbp) that also has a plasmid-like structure (1 kb) (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).
Great 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 mitochondrial genomes, with Silene conica mtDNA containing as many as 11,300,000 base pairs. 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) consists of three circular chromosomes (lengths 1556, 84 and 45 kilobases), which are entirely or largely autonomous with regard to their replication.
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 exist in some protists, as do two unique genome types. One of these unique types is a heterogeneous collection of circular DNA molecules (type 4) while the other is a heterogeneous collection of linear molecules (type 6). Genome types 4 and 6 each range from 1–200 kbp in size.
Endosymbiotic gene transfer, the process by which genes that were coded in the mitochondrial genome are 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.
|1||Animal||No||11–28 kbp||Circular||Single molecule|
|2||Fungi, Plant, Protista||Yes||19–1000 kbp||Circular||Single molecule|
|3||Fungi, Plant, Protista||No||20–1000 kbp||Circular||Large molecule and small plasmid like structures|
|4||Protista||No||1–200 kbp||Circular||Heterogeneous group of molecules|
|5||Fungi, Plant, Protista||No||1–200 kbp||Linear||Homogeneous group of molecules|
|6||Protista||No||1–200 kbp||Linear||Heterogeneous group of molecules|
Mitochondrial DNA is replicated by the DNA polymerase gamma complex which is composed of a 140 kDa catalytic DNA polymerase encoded by the POLG gene and two 55 kDa accessory subunits encoded by the POLG2 gene. The replisome machinery is formed by DNA polymerase, TWINKLE and mitochondrial SSB proteins. TWINKLE is a helicase, which unwinds short stretches of dsDNA in the 5′ to 3′ direction. All these polypeptides are encoded in the nuclear genome.
During embryogenesis, replication of mtDNA is strictly down-regulated from the fertilized oocyte through the preimplantation embryo. The resulting reduction in per-cell copy number of mtDNA plays a role in the mitochondrial bottleneck, exploiting cell-to-cell variability to ameliorate the inheritance of damaging mutations. According to Justin St. John and colleagues, "At the blastocyst stage, the onset of mtDNA replication is specific to the cells of the trophectoderm. In contrast, the cells of the inner cell mass restrict mtDNA replication until they receive the signals to differentiate to specific cell types."
The two strands of the human mitochondrial DNA are distinguished as the heavy strand and the light strand. The heavy strand is rich in guanine and encodes 12 subunits of the oxidative phosphorylation system, two ribosomal RNAs (12S and 16S), and 14 tRNAs. The light strand encodes one subunit, and 8 tRNAs. So, altogether mtDNA encodes for two rRNAs, 22 tRNAs, and 13 proteins subunits, all of which are involved in the oxidative phosphorylation process.
in the mitogenome
|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 oxidase, subunit 1 (complex IV)||05,904–07,445||H|
|MT-CO2||protein coding||Cytochrome c oxidase, subunit 2 (complex IV)||07,586–08,269||H|
|MT-CO3||protein coding||Cytochrome c oxidase, subunit 3 (complex IV)||09,207–09,990||H|
|MT-CYB||protein coding||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-TA||transfer RNA||tRNA-Alanine (Ala or A)||05,587–05,655||L|
|MT-TR||transfer RNA||tRNA-Arginine (Arg or R)||10,405–10,469||H|
|MT-TN||transfer RNA||tRNA-Asparagine (Asn or N)||05,657–05,729||L|
|MT-TD||transfer RNA||tRNA-Aspartic acid (Asp or D)||07,518–07,585||H|
|MT-TC||transfer RNA||tRNA-Cysteine (Cys or C)||05,761–05,826||L|
|MT-TE||transfer RNA||tRNA-Glutamic acid (Glu or E)||14,674–14,742||L|
|MT-TQ||transfer RNA||tRNA-Glutamine (Gln or Q)||04,329–04,400||L|
|MT-TG||transfer RNA||tRNA-Glycine (Gly or G)||09,991–10,058||H|
|MT-TH||transfer RNA||tRNA-Histidine (His or H)||12,138–12,206||H|
|MT-TI||transfer RNA||tRNA-Isoleucine (Ile or I)||04,263–04,331||H|
|MT-TL1||transfer RNA||tRNA-Leucine (Leu-UUR or L)||03,230–03,304||H|
|MT-TL2||transfer RNA||tRNA-Leucine (Leu-CUN or L)||12,266–12,336||H|
|MT-TK||transfer RNA||tRNA-Lysine (Lys or K)||08,295–08,364||H|
|MT-TM||transfer RNA||tRNA-Methionine (Met or M)||04,402–04,469||H|
|MT-TF||transfer RNA||tRNA-Phenylalanine (Phe or F)||00,577–00,647||H|
|MT-TP||transfer RNA||tRNA-Proline (Pro or P)||15,956–16,023||L|
|MT-TS1||transfer RNA||tRNA-Serine (Ser-UCN or S)||07,446–07,514||L|
|MT-TS2||transfer RNA||tRNA-Serine (Ser-AGY or S)||12,207–12,265||H|
|MT-TT||transfer RNA||tRNA-Threonine (Thr or T)||15,888–15,953||H|
|MT-TW||transfer RNA||tRNA-Tryptophan (Trp or W)||05,512–05,579||H|
|MT-TY||transfer RNA||tRNA-Tyrosine (Tyr or Y)||05,826–05,891||L|
|MT-TV||transfer RNA||tRNA-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||Harge subunit : LSU (16S)||01,671–03,229||H|
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 processing, individual mRNA, rRNA, and tRNA sequences are released from the primary transcript. Folded tRNAs therefore act as secondary structure punctuations.
The promoters for the initiation of the transcription of the heavy and light strands are located in the main non-coding region of the mtDNA called the displacement loop, the D-loop. There is evidence that the transcription of the mitochondrial rRNAs is regulated by the heavy-strand promoter 1 (HSP1), and the transcription of the polycistronic transcripts coding for the protein subunits are regulated by HSP2.
Measurement of the levels of the mtDNA-encoded RNAs in bovine tissues has shown that there are major differences in the expression of the mitochondrial RNAs relative to total tissue RNA. Among the 12 tissues examined the highest level of expression was observed in heart, followed by brain and steroidogenic tissue samples.
As demonstrated by the effect of the trophic hormone ACTH on adrenal cortex cells, the expression of the mitochondrial genes may be strongly regulated by external factors, apparently to enhance the synthesis of mitochondrial proteins necessary for energy production. Interestingly, while the expression of protein-encoding genes was stimulated by ACTH, the levels of the mitochondrial 16S rRNA showed no significant change.
In most multicellular organisms, mtDNA is inherited from the mother (maternally inherited). Mechanisms for this include simple dilution (an egg contains on average 200,000 mtDNA molecules, whereas a healthy human sperm has been reported to contain on average 5 molecules), degradation of sperm mtDNA in the male genital tract and 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 inheritance) pattern of mtDNA inheritance is found in most animals, most plants and also in fungi.
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. 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 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 by sequencing the hypervariable control regions (HVR1 or HVR2), and sometimes the complete molecule of the mitochondrial DNA, as a genealogical DNA test. HVR1, for example, consists of about 440 base pairs. These 440 base pairs are compared to the same regions of other individuals (either specific people or subjects in a database) to determine maternal lineage. Most often, the comparison is made with the revised Cambridge Reference Sequence. Vilà et al. have published studies tracing the matrilineal descent of domestic dogs from wolves. The concept of the Mitochondrial Eve is based on the same type of analysis, attempting to discover the origin of humanity by tracking the lineage back in time.
mtDNA is highly conserved, and its relatively slow mutation rates (compared to other DNA regions such as microsatellites) make it 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. However, due to the slow mutation rates, it is often hard to distinguish between closely related species to any large degree, so other methods of analysis must be used.
Entities subject to 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 through a developmental process known as the mtDNA bottleneck. The bottleneck exploits random processes in the cell to increase the cell-to-cell variability in mutant load as an organism develops: a single egg cell with some proportion of mutant mtDNA thus produces an embryo in which 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, with a recent mathematical and experimental metastudy providing evidence for a combination of random partitioning of mtDNAs at cell divisions and random turnover of mtDNA molecules within the cell.
Male mitochondrial DNA inheritance has been discovered in Plymouth Rock chickens. Evidence supports rare instances of male mitochondrial inheritance in some mammals as well. Specifically, documented occurrences exist for mice, where the male-inherited mitochondria were subsequently rejected. It has also been found in sheep, and in cloned cattle. Rare cases of male mitochondrial inheritance have been documented in humans. 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.
Doubly uniparental inheritance of mtDNA is observed in bivalve mollusks. In those species, females have only one type of mtDNA (F), whereas males have F type mtDNA in their somatic cells, but M type of mtDNA (which can be as much as 30% divergent) in germline cells. Paternally inherited mitochondria have additionally been reported in some insects such as fruit flies, honeybees, and periodical cicadas.
An IVF technique known as mitochondrial donation or mitochondrial replacement therapy (MRT) results in offspring containing mtDNA from a donor female, and nuclear 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. 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.
The concept that mtDNA is particularly susceptible to reactive oxygen species generated by the respiratory chain due to its proximity remains controversial. mtDNA does not accumulate any more oxidative base damage than nuclear DNA. It has been reported that at least some types of oxidative DNA damage are repaired more efficiently in mitochondria than they are in the nucleus. mtDNA is packaged with proteins which appear to be as protective as proteins of the nuclear chromatin. Moreover, mitochondria evolved a unique mechanism which maintains mtDNA 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 mtDNA present in mitochondria  The outcome of mutation in mtDNA may be an alteration in the coding instructions for some proteins, which may have an effect on organism metabolism and/or fitness.
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 heart, eye, and muscle movements. Some evidence suggests that they might be major contributors to the aging process and age-associated pathologies. 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  and are influenced by complicated stochastic processes within the cell and during development.
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.
Though the idea is controversial, some evidence suggests a link between aging and mitochondrial genome dysfunction. In essence, mutations in mtDNA 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. 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. Once, there was thought to be a positive feedback loop at work (a 'Vicious Cycle'); as mitochondrial 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. However, this concept was conclusively disproved when it was demonstrated that mice, which were genetically altered to accumulate mtDNA mutations at accelerated rate do age prematurely, but their tissues do not produce more ROS as predicted by the 'Vicious Cycle' hypothesis. Supporting a link between longevity and mitochondrial DNA, some studies have found correlations between biochemical properties of the mitochondrial DNA and the longevity of species. 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. 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.
The brains of individuals with Alzheimer’s disease have elevated levels of oxidative DNA damage in both nuclear DNA and mtDNA, but the mtDNA has approximately 10-fold higher levels than nuclear DNA. It has been proposed that aged mitochondria is the critical factor in the origin of neurodegeneration in Alzheimer’s disease.
In Huntington’s disease, mutant huntingtin protein causes mitochondria dysfunction involving inhibition of mitochondrial electron transport, higher levels of reactive oxygen species and increased oxidative stress. Mutant huntingtin protein promotes oxidative damage to mtDNA, as well as nuclear DNA, that may contribute to Huntington’s disease pathology.
The DNA oxidation product 8-oxoguanine (8-oxoG) is a well-established marker of oxidative DNA damage. In persons with amyotrophic lateral sclerosis (ALS), the enzymes that normally repair 8-oxoG DNA damages in the mtDNA of spinal motor neurons are impaired. Thus oxidative damage to mtDNA of motor neurons may be a significant factor in the etiology of ALS.
Over the past decade, an Israeli research group led by Professor Vadim Fraifeld has shown that extraordinarily strong and significant correlations exist between the mtDNA base composition and animal species-specific maximum life spans. As demonstrated in their work, higher mtDNA guanine + cytosine content (GC%) strongly associates with longer maximum life spans across animal species. An additional astonishing observation is that the mtDNA GC% correlation with the maximum life spans is independent of the well-known correlation between animal species metabolic rate and maximum life spans. The mtDNA 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 mtDNA GC% * metabolic rate). To support the scientific community in carrying out comparative analyses between mtDNA features and longevity across animals, a dedicated database was built named MitoAge.
Deletion breakpoints frequently occur within or near regions showing non-canonical (non-B) conformations, namely hairpins, cruciforms and cloverleaf-like elements. 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. Recently (2017) was found that all mitochodrial genomes sequenced so far contain many of inverted repeats necessary for cruciform DNA formation and these loci are particularly enriched in replication origin sites, D-loops and stem loops.
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 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, 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.
The 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) among different species. 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. mtDNA can be used to estimate the relationship between both closely related and distantly related species. Due to the high mutation rate of mtDNA 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
Mitochondrial DNA was admitted into evidence for the first time ever in a United States courtroom in 1996 during State of Tennessee v. Paul Ware.
In the 1998 United States court case of Commonwealth of Pennsylvania v. Patricia Lynne Rorrer, mitochondrial DNA was admitted into evidence in the State of Pennsylvania for the first time. The case was featured in episode 55 of season 5 of the true crime drama series Forensic Files (season 5).
Mitochondrial DNA was first admitted into evidence in California, United States, 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. This was the first trial in the U.S. to admit canine DNA.
Mitochondrial DNA was discovered in the 1960s by Margit M. K. Nass and Sylvan Nass by electron microscopy as DNase-sensitive threads inside mitochondria, and by Ellen Haslbrunner, Hans Tuppy and Gottfried Schatz by biochemical assays on highly purified mitochondrial fractions.
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.
Several specialized databases exist that report polymorphisms and mutations in the human mitochondrial DNA, together with the assessment of their pathogenicity.
A haplotype is a group of alleles in an organism that are inherited together from a single parent, and a haplogroup (haploid from the Greek: ἁπλούς, haploûs, "onefold, simple" and English: Group) is a group of similar haplotypes that share a common ancestor with a single-nucleotide polymorphism mutation. More specifically, a haplogroup is a combination of alleles at different chromosomes regions that are closely linked and that tend to be inherited together. As a haplogroup consists of similar haplotypes, it is usually possible to predict a haplogroup from haplotypes. Haplogroups pertain to a single line of descent. As such, membership of a haplogroup, by any individual, relies on a relatively small proportion of the genetic material possessed by that individual.
Each haplogroup originates from, and remains part of, a preceding single haplogroup (or paragroup). As such, any related group of haplogroups may be precisely modelled as a nested hierarchy, in which each set (haplogroup) is also a subset of a single broader set (as opposed, that is, to biparental models, such as human family trees).
Haplogroups are normally identified by an initial letter of the alphabet, and refinements consist of additional number and letter combinations, such as (for example) A → A1 → A1a.
In human genetics, the haplogroups most commonly studied are Y-chromosome (Y-DNA) haplogroups and mitochondrial DNA (mtDNA) haplogroups, each of which can be used to define genetic populations. Y-DNA is passed solely along the patrilineal line, from father to son, while mtDNA is passed down the matrilineal line, from mother to offspring of both sexes. Neither recombines, and thus Y-DNA and mtDNA change only by chance mutation at each generation with no intermixture between parents' genetic material.Haplogroup CZ (mtDNA)
In human mitochondrial genetics, the Haplogroup CZ is a human mitochondrial DNA (mtDNA) haplogroup.Haplogroup JT (mtDNA)
Haplogroup JT is a human mitochondrial DNA (mtDNA) haplogroup.Haplogroup L6 (mtDNA)
In human mitochondrial genetics, Haplogroup L6 is a human mitochondrial DNA (mtDNA) haplogroup. It is a small African haplogroup.Haplogroup P (mtDNA)
In human mitochondrial genetics, Haplogroup P is a human mitochondrial DNA (mtDNA) haplogroup.Haplogroup Q (mtDNA)
In human mitochondrial genetics, haplogroup Q is a human mitochondrial DNA (mtDNA) haplogroup typical for Oceania. It is a subgroup of haplogroup M29'Q.Haplogroup R0 (mtDNA)
Haplogroup R0 (formerly known as haplogroup pre-HV) is a human mitochondrial DNA (mtDNA) haplogroup.Haplogroup R (mtDNA)
Haplogroup R is a widely distributed human mitochondrial DNA (mtDNA) haplogroup. Haplogroup R
is associated with the peopling of Eurasia after about 70,000 years ago, and is distributed in modern populations throughout the world outside of sub-Saharan Africa.Haplogroup R is a descendant of the macro-haplogroup N. Among the R clade's descendant haplogroups are B, U (and thus K), F, R0 (and thus HV, H, and V), and JT (the ancestral haplogroup of J and T).Haplogroup T (mtDNA)
Haplogroup T is a human mitochondrial DNA (mtDNA) haplogroup. It is believed to have originated around 25,100 years ago in the Near East.Haplogroup V (mtDNA)
Haplogroup V is a human mitochondrial DNA (mtDNA) haplogroup. The clade is believed to have originated around 9,800 years ago in the Near East.Human mitochondrial DNA haplogroup
In human genetics, a human mitochondrial DNA haplogroup is a haplogroup defined by differences in human mitochondrial DNA. Haplogroups are used to represent the major branch points on the mitochondrial phylogenetic tree. Understanding the evolutionary path of the female lineage has helped population geneticists trace the matrilineal inheritance of modern humans back to human origins in Africa and the subsequent spread around the globe.
The letter names of the haplogroups (not just mitochondrial DNA haplogroups) run from A to Z. As haplogroups were named in the order of their discovery, the alphabetical ordering does not have any meaning in terms of actual genetic relationships.
The hypothetical woman at the root of all these groups (meaning just the mitochondrial DNA haplogroups) is the matrilineal most recent common ancestor (MRCA) for all currently living humans. She is commonly called Mitochondrial Eve.
The rate at which mitochondrial DNA mutates is known as the mitochondrial molecular clock. It's an area of ongoing research with one study reporting one mutation per 8000 years.Human mitochondrial genetics
Human mitochondrial genetics is the study of the genetics of human mitochondrial DNA (the DNA contained in human mitochondria). The human mitochondrial genome is the entirety of hereditary information contained in human mitochondria. Mitochondria are small structures in cells that generate energy for the cell to use, and are hence referred to as the "powerhouses" of the cell.
Mitochondrial DNA (mtDNA) is not transmitted through nuclear DNA (nDNA). In humans, as in most multicellular organisms, mitochondrial DNA is inherited only from the mother's ovum. There are theories, however, that paternal mtDNA transmission in humans can occur under certain circumstances.Mitochondrial inheritance is therefore non-Mendelian, as Mendelian inheritance presumes that half the genetic material of a fertilized egg (zygote) derives from each parent.
Eighty percent of mitochondrial DNA codes for mitochondrial RNA, and therefore most mitochondrial DNA mutations lead to functional problems, which may be manifested as muscle disorders (myopathies).
Because they provide 30 molecules of ATP per glucose molecule in contrast to the 2 ATP molecules produced by glycolysis, mitochondria are essential to all higher organisms for sustaining life. The mitochondrial diseases are genetic disorders carried in mitochondrial DNA, or nuclear DNA coding for mitochondrial components. Slight problems with any one of the numerous enzymes used by the mitochondria can be devastating to the cell, and in turn, to the organism.Mitochondrial DNA depletion syndrome
Mitochondrial DNA depletion syndrome (MDS or MDDS) is any of a group of autosomal recessive disorders that cause a significant drop in mitochondrial DNA in affected tissues. Symptoms can be any combination of myopathic, hepatopathic, or encephalomyopathic. These syndromes affect tissue in the muscle, liver, or both the muscle and brain, respectively. The condition is typically fatal in infancy and early childhood, though some have survived to their teenage years with the myopathic variant and some have survived into adulthood with the SUCLA2 encephalomyopathic variant. There is currently no curative treatment for any form of MDDS, though some preliminary treatments have shown a reduction in symptoms.Mitochondrial Eve
In human genetics, the Mitochondrial Eve (also mt-Eve, mt-MRCA) is the matrilineal most recent common ancestor (MRCA) of all currently living humans, i.e., the most recent woman from whom all living humans descend in an unbroken line purely through their mothers, and through the mothers of those mothers, back until all lines converge on one woman.
In terms of mitochondrial haplogroups, the mt-MRCA is situated at the divergence of macro-haplogroup L into L0 and L1–6. As of 2013, estimates on the age of this split ranged at around 150,000 years ago,
consistent with a date later than the speciation of Homo sapiens but earlier than the recent out-of-Africa dispersal.The male analog to the "Mitochondrial Eve" is the "Y-chromosomal Adam" (or Y-MRCA), the individual from whom all living humans are patrilineally descended. As the identity of both matrilineal and patrilineal MRCAs is dependent on genealogical history (pedigree collapse), they need not have lived at the same time.
As of 2013, estimates for the age Y-MRCA are subject to substantial uncertainty, with a wide range of times from 180,000 to 580,000 years ago (with an estimated age of between 120,000 and 156,000 years ago, roughly consistent with the estimate for mt-MRCA.).The name "Mitochondrial Eve" alludes to biblical Eve. This led to repeated misrepresentations or misconceptions in journalistic accounts on the topic. Popular science presentations of the topic usually point out such possible misconceptions by emphasizing the fact that the position of mt-MRCA is neither fixed in time (as the position of mt-MRCA moves forward in time as mitochondrial DNA (mtDNA) lineages become extinct), nor does it refer to a "first woman", nor the only living female of her time, nor the first member of a "new species".Mitochondrial disease
Mitochondrial diseases are a group of disorders caused by dysfunctional mitochondria, the organelles that generate energy for the cell. Mitochondria are found in every cell of the human body except red blood cells, and convert the energy of food molecules into the ATP that powers most cell functions.
Mitochondrial diseases are sometimes (about 15% of the time) caused by mutations in the mitochondrial DNA that affect mitochondrial function. Other mitochondrial diseases are caused by mutations in genes of the nuclear DNA, whose gene products are imported into the mitochondria (mitochondrial proteins) as well as acquired mitochondrial conditions. Mitochondrial diseases take on unique characteristics both because of the way the diseases are often inherited and because mitochondria are so critical to cell function. The subclass of these diseases that have neuromuscular disease symptoms are often called a mitochondrial myopathy.Mitochondrion
The mitochondrion (plural mitochondria) is a double-membrane-bound organelle found in most eukaryotic organisms. Some cells in some multicellular organisms may, however, lack them (for example, mature mammalian red blood cells). A number of unicellular organisms, such as microsporidia, parabasalids, and diplomonads, have also reduced or transformed their mitochondria into other structures. To date, only one eukaryote, Monocercomonoides, is known to have completely lost its mitochondria. The word mitochondrion comes from the Greek μίτος, mitos, "thread", and χονδρίον, chondrion, "granule" or "grain-like". Mitochondria generate most of the cell's supply of adenosine triphosphate (ATP), used as a source of chemical energy. A mitochondrion is thus termed the powerhouse of the cell.Mitochondria are commonly between 0.75 and 3 μm² in area but vary considerably in size and structure. Unless specifically stained, they are not visible. In addition to supplying cellular energy, mitochondria are involved in other tasks, such as signaling, cellular differentiation, and cell death, as well as maintaining control of the cell cycle and cell growth. Mitochondrial biogenesis is in turn temporally coordinated with these cellular processes. Mitochondria have been implicated in several human diseases, including mitochondrial disorders, cardiac dysfunction, heart failure and autism.The number of mitochondria in a cell can vary widely by organism, tissue, and cell type. For instance, red blood cells have no mitochondria, whereas liver cells can have more than 2000. The organelle is composed of compartments that carry out specialized functions. These compartments or regions include the outer membrane, the intermembrane space, the inner membrane, and the cristae and matrix.
Although most of a cell's DNA is contained in the cell nucleus, the mitochondrion has its own independent genome that shows substantial similarity to bacterial genomes. Mitochondrial proteins (proteins transcribed from mitochondrial DNA) vary depending on the tissue and the species. In humans, 615 distinct types of protein have been identified from cardiac mitochondria, whereas in rats, 940 proteins have been reported. The mitochondrial proteome is thought to be dynamically regulated.Nuclear DNA
Nuclear DNA (nDNA), or nuclear deoxyribonucleic acid, is the DNA contained within each cell nucleus of a eukaryotic organism. Nuclear DNA encodes for the majority of the genome in eukaryotes, with mitochondrial DNA and plastid DNA coding for the rest. Nuclear DNA adheres to Mendelian inheritance, with information coming from two parents, one male and one female, rather than matrilineally (through the mother) as in mitochondrial DNA.POLG
DNA polymerase subunit gamma (POLG or POLG1) is an enzyme that in humans is encoded by the POLG gene. Mitochondrial DNA polymerase is heterotrimeric, consisting of a homodimer of accessory subunits plus a catalytic subunit. The protein encoded by this gene is the catalytic subunit of mitochondrial DNA polymerase. Defects in this gene are a cause of progressive external ophthalmoplegia with mitochondrial DNA deletions 1 (PEOA1), sensory ataxic neuropathy dysarthria and ophthalmoparesis (SANDO), Alpers-Huttenlocher syndrome (AHS), and mitochondrial neurogastrointestinal encephalopathy syndrome (MNGIE).Paternal mtDNA transmission
In genetics, paternal mtDNA transmission and paternal mtDNA inheritance refer to the incidence of mitochondrial DNA (mtDNA) 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 offspring, making it an example of non-Mendelian inheritance. In contrast, mtDNA transmission from both parents occurs regularly in certain bivalves.
Types of nucleic acids
|Ribonucleic acids |
|Other/to be sorted|
see also mitochondrial diseases