Mitochondrial DNA
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Mitochondrial DNA (mtDNA) is the DNA located in organelles called mitochondria, structures within cells that convert the energy from food into a form that cells can use. Most other DNA present in eukaryotic organisms is found in the cell nucleus.
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. 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 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 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 can in some cases cause maternally inherited diseases and some evidence suggests that they might be major contributors to the aging process and age-associated pathologies.
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 double-stranded circular mtDNA molecule consists of 15,000-17,000 base pairs. 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 (tRNA) and two are 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.
MtDNA is replicated by the DNA polymerase gamma complex which is composed of a 140 kDa catalytic DNA polymerase encoded by the POLG gene and a 55 kDa accessory subunit encoded by the POLG2 gene.
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Mitochondrial inheritance
Female inheritance
In 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. 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 maternal lineage far back in time. (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 regions (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 Cambridge Reference Sequence. Vilà et al. have published studies tracing the matrilineal descent of domestic dogs to 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.
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 research into a person's maternal line.
Male inheritance
It has been reported that mitochondria can occasionally be inherited from the father in some species such as mussels. Paternally inherited mitochondria have additionally been reported in some insects such as fruit flies, honeybees, and periodical cicadas.
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 and was linked to infertility.
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
Transport chain
Many of the genes encode the transport chain:
| Category | Genes |
| NADH dehydrogenase (complex I) | MT-ND1, MT-ND2, MT-ND3, MT-ND4, MT-ND4L, MT-ND5, MT-ND6 |
| Coenzyme Q - cytochrome c reductase/Cytochrome b (complex III) | MT-CYB |
| cytochrome c oxidase (complex IV) | MT-CO1, MT-CO2, MT-CO3 |
| ATP synthase | MT-ATP6, MT-ATP8 |
rRNA
Mitochondrial rRNA is encoded by MT-RNR1 (12S) and MT-RNR2 (16S).
tRNA
The following genes encode tRNA:
| Amino Acid | 3-Letter | 1-Letter | MT DNA |
|---|---|---|---|
| Alanine | Ala | A | MT-TA |
| Arginine | Arg | R | MT-TR |
| Asparagine | Asn | N | MT-TN |
| Aspartic acid | Asp | D | MT-TD |
| Cysteine | Cys | C | MT-TC |
| Glutamic acid | Glu | E | MT-TE |
| Glutamine | Gln | Q | MT-TQ |
| Glycine | Gly | G | MT-TG |
| Histidine | His | H | MT-TH |
| Isoleucine | Ile | I | MT-TI |
| Leucine | Leu | L | MT-TL1, MT-TL2 |
| Lysine | Lys | K | MT-TK |
| Methionine | Met | M | MT-TM |
| Phenylalanine | Phe | F | MT-TF |
| Proline | Pro | P | MT-TP |
| Serine | Ser | S | MT-TS1, MT-TS2 |
| Threonine | Thr | T | MT-TT |
| Tryptophan | Trp | W | MT-TW |
| Tyrosine | Tyr | Y | MT-TY |
| Valine | Val | V | MT-TV |
External links
- Mitomap - a human mitochondrial genome database [1]
- Defining mutations of mtDNA haplogroups and subclades
- MitoSearch : public mtDNA database
- mtDNA mutation rates
- A polymorphism in mitochondrial DNA associated with IQ?
- mtDNA and the global diaspora of modern humans Professor Stephen Oppenheimer's Genetic Map
- EMPOP - Mitochondrial DNA Control Region Database
License
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Mitochondrial DNA".
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