Instruct: Given a question, retrieve documents that can help answer the question.
Query: Who discovered mitochondrial 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,[97] and by Ellen Haslbrunner, Hans Tuppy and Gottfried Schatz by biochemical assays on highly purified mitochondrial fractions.[98]
In 1967, it was discovered that mitochondria contained ribosomes. In 1968, methods were developed for mapping the mitochondrial genes, with the genetic and physical map of yeast mitochondrial DNA being completed in 1976.
The near-absence of genetic recombination in mitochondrial DNA makes it a useful source of information for scientists involved in population genetics and evolutionary biology. Because all the mitochondrial DNA is inherited as a single unit, or haplotype, the relationships between mitochondrial DNA from different individuals can be represented as a gene tree. Patterns in these gene trees can be used to infer the evolutionary history of populations. The classic example of this is in human evolutionary genetics, where the molecular clock can be used to provide a recent date for mitochondrial Eve. This is often interpreted as strong support for a recent modern human expansion out of Africa. Another human example is the sequencing of mitochondrial DNA from Neanderthal bones. The relatively large evolutionary distance between the mitochondrial DNA sequences of Neanderthals and living humans has been interpreted as evidence for the lack of interbreeding between Neanderthals and anatomically modern humans.
In addition to nuclear DNA, humans (like almost all eukaryotes) have mitochondrial DNA. Mitochondria, the "power houses" of a cell, have their own DNA. Mitochondria are inherited from one's mother, and their DNA is frequently used to trace maternal lines of descent (see mitochondrial Eve). Mitochondrial DNA is only 16kb in length and encodes for 62 genes.
However, the mitochondrial DNA (mtDNA) is immune to sexual mixing, unlike the nuclear DNA whose chromosomes are shuffled and recombined in Mendelian inheritance. Mitochondrial DNA, therefore, can be used to trace matrilineal inheritance and to find the Mitochondrial Eve (also known as the "African Eve"), the most recent common ancestor of all humans via the mitochondrial DNA pathway.
Circulating mitochondrial DNA, also called cell-free circulating mitochondrial DNA and circulating cell-free mitochondrial DNA (ccf mtDNA), are short sections of mitochondrial DNA (mtDNA) that are released by cells undergoing stress or other damaging or pathological events. Circulating mitochondrial DNA is recognized by the immune system and activates inflammatory reactions. It is also a biomarker that can be used to detect the degree of damage from myocardial infarctions, cancers and ordinary stress. In certain situations it acts as a hormone.
Wallace is a pioneer in the study of mitochondrial DNA. Wallace and his colleagues introduced human mitochondrial genetics into the field of molecular genetics. In 1975, for the first time ever, Wallace could associate a genetic disorder with the mitochondrial DNA region (resistance to chloramphenicol) and in 1990 he described a mitochondrial DNA mutation as the cause of a particular form of myoclonic epilepsy. He has been instrumental in the study of the mitochondrial genome and has developed new methods for the analysis of mitochondrial DNA.
Mitochondrial DNA is an academic journal that publishes review articles on the current and developing technologies around mitochondrial DNA research and discovery. It is published by Informa Healthcare.
The cytosolic, intermembrane space, compartment has a water content of 3.8 μl/mg protein, while the mitochondrial matrix 0.8 μl/mg protein. It is not known how mitochondria maintain osmotic balance across the inner mitochondrial membrane, although the membrane contains aquaporins that are believed to be conduits for regulated water transport. Mitochondrial matrix has a pH of about 7.8. Mitochondrial DNA was discovered by Nash and Margit in 1963. One to many double stranded mainly circular DNA is present in mitochondrial matrix. Mitochondrial DNA is 1% of total DNA of a cell. It is rich in Guanine and Cytosine content. Mitochondria of mammals have 55s ribosomes.
The mussel "Mytilus edulis" is an anomaly in terms of mitochondrial DNA inheritance. Unlike almost all animals, this species has biparental inheritance for mitochondrial DNA, meaning that both the male and the female contribute mitochondria to the offspring. This was discovered when researchers realized that most individuals of a "Mytilus edulis" population were heteroplasmic. Researchers also believe that this could be a by-product of species hybridization.
Clade CoRR hypothesis Haplogroup Heteroplasmy Human mitochondrial DNA haplogroup Human mitochondrial genetics Mitochondrial disease Mitochondrial DNA (journal) Mitochondrial Eve Mitochondrial rCRS Paternal mtDNA transmission Single origin theory Supercluster (genetic) TIM/TOM complex
Since the LIG3 gene encodes the only DNA ligase in mitochondria, inactivation of the LIG3 gene results in loss of mitochondrial DNA that in turn leads to loss of mitochondrial function. Fibroblasts with inactivated Lig3 gene can be propagated in the media supplemented with uridine and pyruvate. However, these cells lack mtDNA. Physiological levels of mitochondrial DNA ligase III appear excessive, and cells with 100-fold reduced mitochondrial content of mitochondrial DNA ligase III-alpha maintain normal mtDNA copy number. The essential role of DNA ligase III-alpha in mitochondrial DNA metabolism can be fulfilled by other DNA ligases, including the NAD-dependent DNA ligase of "E. coli", if they are targeted to mitochondria. Thus, viable cells that lack nuclear DNA ligase III-alpha can be generated. While DNA ligase I is the predominant enzyme that joins Okazaki fragments during DNA replication, it is now evident that the DNA ligase III-alpha/XRCC1 complex enables cells that either lack or have reduced DNA ligase I activity to complete DNA replication. Given the biochemical and cell biology studies linking the DNA ligase III-alpha/XRCC1 complex with excision repair and the repair of DNA single strand breaks, it was surprising that the cells lacking nuclear DNA ligase III-alpha did not exhibit significantly increased sensitivity to DNA damaging agent. These studies suggest that there is significant functional redundancy between DNA ligase I and DNA ligase III-alpha in these nuclear DNA repair pathways. In mammalian cells, most DNA double strand breaks are repaired by DNA ligase IV-dependent non-homologous end joining (NHEJ). DNA ligase III-alpha participates in a minor alternative NHEJ pathway that generates chromosomal translocations. Unlike the other nuclear DNA repair functions, it appears that the role of DNA ligase III-alpha in alternative NHEJ is independent of XRCC1.
Apoptosis Inducing Factor (AIF) is a protein that triggers chromatin condensation and DNA fragmentation in a cell in order to induce programmed cell death. The mitochondrial AIF protein was found to be a caspase-independent death effector that can allow independent nuclei to undergo apoptotic changes. The process triggering apoptosis starts when the mitochondria releases AIF, which exits through the mitochondrial membrane, enters the cytosol, and finally ends up in the cell nucleus where it signals the cell to condense its chromosomes and fragment its DNA molecules in order to prepare for cell death. Recently, researchers have discovered that AIF's activity is dependent upon the type of cell, the apoptotic insult, and its DNA-binding ability. AIF also plays a significant role in the mitochondrial respiratory chain and metabolic redox reactions.
Botkin and his wife had four children, daughter Marina and sons Nikita, Peter, and Yevgeny. He also had a stepdaughter, Kira. His daughter Marina Botkina Schweitzer's DNA was later used to help identify the remains of her grandfather, Yevgeny Botkin, after they were exhumed along with other Romanovs in 1991 from a mass grave discovered in Ganina Yama near Yekaterinburg. Schweitzer's DNA was compared against the DNA of her maternal half-sister Kira, who also gave a blood sample, to help scientists isolate the DNA Schweitzer shared in common with her grandfather. This enabled scientists to create a "Botkin DNA profile" and use it to positively identify Dr. Botkin. Scientists in the early 1990s were unable to identify Dr. Botkin using mitochondrial DNA, or DNA that is passed down from mother to child, as they used it to identify the Romanovs. Schweitzer was descended from Dr. Botkin in the paternal line and didn't share mitochondrial DNA with her father and grandfather.
Homoplasmy is a term used in genetics to describe a eukaryotic cell whose copies of mitochondrial DNA are all identical. In normal and healthy tissues, all cells are homoplasmic. Homoplasmic mitochondrial DNA copies may be normal or mutated; however, most mutations are heteroplasmic (only occurring in some copies of mitochondrial DNA). It has been discovered, though, that homoplasmic mitochondrial DNA mutations may be found in human tumors.
As mentioned above, DNA ligase III-alpha mRNA encodes nuclear and mitochondrial versions of DNA ligase III-alpha. Nuclear DNA ligase III-alpha exists and functions in a stable complex with the DNA repair protein XRCC1. These proteins interact via their C-terminal BRCT domains. XRCC1 has no enzymatic activity but instead appears to acts as a scaffold protein by interacting with a large number of proteins involved in base excision and single-strand break repair. The participation of XRCC1 in these pathways is consistent with the phenotype of xrcc1 cells. In contrast to nuclear DNA ligase III-alpha, mitochondrial DNA ligase III-alpha functions independently of XRCC1, which is not found in mitochondria. It appears that nuclear DNA ligase III-alpha forms a complex with XRCC1 in the cytoplasm and the subsequent nuclear targeting of the resultant complex is directed by the XRCC1 nuclear localization signal. While mitochondrial DNA ligase III-alpha also interacts with XRCC1, it is likely that the activity of the mitochondrial targeting sequence of DNA ligase III-alpha is greater than the activity of the XRCC1 nuclear localization signal and that the DNA ligase III-alpha/XRCC1 complex is disrupted when mitochondrial DNA ligase III-alpha passes through the mitochondrial membrane.
One variation of the idea that mutation is the basis of aging, that has received much attention, is that mutations specifically in mitochondrial DNA are the cause of aging. Several studies have shown that mutations accumulate in mitochondrial DNA in infrequently replicating cells with age. DNA polymerase gamma is the enzyme that replicates mitochondrial DNA. A mouse mutant with a defect in this DNA polymerase is only able to replicate its mitochondrial DNA inaccurately, so that it sustains a 500-fold higher mutation burden than normal mice. These mice showed no clear features of rapidly accelerated aging. Overall, the observations discussed in this section indicate that mutations are not the primary cause of aging.
According to a recent investigation by Wong, Liang, Kwon, Bai, Alper and Gropman, TGGE can be utilized to examine the mitochondrial DNA of an individual. According to these authors, TGGE was utilized to determine two novel mutations in the mitochondrial genome: "A 21-year-old woman who has been suspected of mitochondrial cytopathy, but negative for common mitochondrial DNA (mtDNA) point mutations and deletions, was screened for unknown mutations in the entire mitochondrial genome by temperature gradient gel electrophoresis".
Mitochondrial DNA (mtDNA or mDNA)[3] 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.
Specific analysis of tumor-derived circulating mitochondrial DNA is challenging in human samples as it requires to track in plasma defined mutations, or alterations from the mitochondrial genome. In animal models, separating tumor-derived DNA in plasma from non-tumor derived DNA is easier. A proof of principle demonstrated the sensitivity of detecting tumor-derived circulating mitochondrial DNA in the plasma, CSF and urine of xenografted animals. 
Mitochondrial DNA mutations occur frequently, due to the lack of the error checking capability that nuclear DNA has (see Mutation rate). This means that mitochondrial DNA disorders may occur spontaneously and relatively often. Defects in enzymes that control mitochondrial DNA replication (all of which are encoded for by genes in the nuclear DNA) may also cause mitochondrial DNA mutations.
Male mitochondrial DNA inheritance has been discovered in Plymouth Rock chickens.[27] Evidence supports rare instances of male mitochondrial inheritance in some mammals as well. Specifically, documented occurrences exist for mice,[28][29] where the male-inherited mitochondria were subsequently rejected. It has also been found in sheep,[30] and in cloned cattle.[31] Rare cases of male mitochondrial inheritance have been documented in humans.[32][33] 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.
Coverage includes:Previously published under the title "DNA Sequence" (Vols 1-19.3), "Mitochondrial DNA" accepts original high-quality reports based on mapping, sequencing and analysis of mitochondrial DNA and RNA. Descriptive papers on DNA sequences from mitochondrial genomes, and also analytical papers in the areas of population genetics, medical genetics, phylogenetics and human evolution that use mitochondrial DNA as a source of evidence for studies will be considered for publication. The editorial board will also consider manuscripts that examine population genetic and systematic theory that specifically address the use of mitochondrial DNA sequences, as well as papers that discuss the utility of mitochondrial DNA information in medical studies and in human evolutionary biology.
Nuclear DNA and mitochondrial DNA differ in many ways, starting with location and structure. Nuclear DNA is located within the nucleus of eukaryote cells and usually has two copies per cell while mitochondrial DNA is located in the mitochondria and contains 100-1,000 copies per cell. The structure of nuclear DNA chromosomes is linear with open ends and includes 46 chromosomes containing 3 billion nucleotides. Mitochondrial DNA chromosomes usually have closed, circular structures, and contain for example 16,569 nucleotides in human. Nuclear DNA is diploid, ordinarily inheriting the DNA from two parents, while mitochondrial DNA is haploid, coming only from the mother. The mutation rate for nuclear DNA is less than 0.3% while that of mitochondrial DNA is generally higher.
Schatz played a leading role in elucidating the biogenesis of mitochondria and in discovering mitochondrial DNA. He recognized that this DNA encoded only a small number of mitochondrial proteins which was decisive for his further research on the import of proteins into the mitochondria and the degradation of proteins within these organelles. Schatz discovered a complex transport system that recognizes mitochondrial proteins made in the cytoplasm by specific signals attached to these proteins and then transfers them into the mitochondria. This system comprises two protein complexes, TOM and TIM, which are localized in the outer and inner mitochondrial membranes respectively. Mutations in these complexes can disrupt protein import and cause illnesses such as the neurodegenerative Mohr-Tranebjaerg syndrome, which leads to deafness. Schatz also demonstrated that the energy-requiring protease Lon regulates protein turnover within the mitochondria, thus maintaining the integrity and the proper functioning of mitochondrial DNA. Gottfried Schatz is the author of more than 200 scientific publications, three volumes of essays, an autobiography and a novel. His books have appeared in English, French, Greek and Czech translation.