CDC: Tomatoes eyed in salmonella cases in 9 states

ATLANTA - An outbreak of salmonella food poisoning first linked to uncooked tomatoes has now been reported in nine states, US health officials said Tuesday.Lab tests have confirmed 40 illnesses in Texas and New Mexico as the same type of salmonella, right down to the genetic fingerprint. An investigation by Texas and New Mexico health authorities and the Indian Health Service tied those cases to uncooked, raw, large tomatoes.At least 17 people in Texas and New Mexico have been hospitalized. None have died, according to the US Centers for Disease Control and Prevention.Another 30 people have become sick with the same Salmonella Saintpaul infection in Arizona, Utah, Colorado, Kansas, Idaho, Illinois and Indiana. CDC investigators are looking into whether tomatoes were culprits there, too.In Texas and New Mexico, raw large tomatoes — including Roma and red round tomatoes — were found to be a common factor in the 40 illnesses. But no farm, distributor or grocery chain has been identified as the main source, said Casey Barton Behravesh, a CDC epidemiologist working on the investigation."The specific type and source of tomatoes is under investigation," she said.Salmonella is a bacterial infection that lives in the intestinal tracts of humans and other animals. The bacteria are usually transmitted to humans by eating foods contaminated with animal feces.Most infected people suffer fever, diarrhea and abdominal cramps starting 12 to 72 hours after infection. The illness tends to last four to seven days.Many people recover without treatment. However, severe infection and even death is possible. Infants, the elderly and people with weakened immune systems are at greatest risk for severe infections.In Texas and New Mexico, the patients ranged in age from ages 3 to 82. Of the 40, 38 were interviewed. Most said they ate raw tomatoes from either stores or restaurants before becoming ill between April 23 and May 27.Another 17 cases are under investigation in New Mexico, CDC officials said. - AP



Source:GMANEWS.TV

Human mitochondrial genetics

Mitochondrial genetics is the study of the genetics of the DNA contained in 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), and in most multicellular organisms, virtually all mitochondria are inherited from the mother's ovum, as it is unusual for sperm cells to contribute mitochondria when fertilising ova.
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 functional mitochondrial proteins, and therefore most mitochondrial DNA mutations lead to functional problems, which may be manifested as muscle disorders (myopathies).
Understanding the genetic mutations that affect mitochondria can help us to understand the inner workings of cells and organisms, as well as helping to suggest methods for successful therapeutic tissue and organ cloning, and to treatments or possibly cures for many devastating muscular disorders.

Mitochondrial function and genome

Because they provide 36 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 specifically in mitochondrial DNA; 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.

Membrane complexes

The processes carried out by the electron transport chain are mediated by protein complexes (named Complexes I-V, DHO-QO, ETF-QO, and ANT). Complex I, or NADH : coenzyme Q oxidoreductase, uses the energy in NADH to pump protons into the intermembrane space of the mitochondrion, pumping 2 protons per electron and passing 2 electrons via coenzyme Q to complex III or coenzyme Q: cytochrome c oxidoreductase. Complex II or succinate : coenzyme Q oxidoreductase accepts energy from succinate produced in the citric acid cycle and passes it via coenzyme Q to complex III. Complex III pumps 1 protons per electron and passes 1 electron via cytochrome c to complex IV. Complex IV pumps 1 protons into the space between the mitochondrion’s two membranes before passing the electron to O2 which reacts to form water. Complex V (ATP synthase) is a rotary complex which allows approximately (determining the actual number is very difficult) 10 protons to enter the mitochondrial matrix along their concentration gradients. It uses the energy from the gradient to form the bond between ADP and the phosphate group to create ATP. The electron transfer flavoprotein : coenzyme Q oxidoreductase is also an electron-transporting molecule and is involved in the breakdown of fatty acids and amino acids. ANT (adenine nucleotide translocator) is also involved in oxidative phosphorylation as an energy carrying molecule. Each of these eight complexes plays a vital role in the health of the cell and any slight mutation in any one of the proteins that make up these complexes can lead to cell death or stress, which can both in turn lead to a number of diseases.

Genome

Mitochondrial DNA (mtDNA) is present in mitochondria as a circular molecule and in most species codes for 13 or 14 proteins involved in the electron transfer chain, 2 rRNA subunits and 22 tRNA molecules (all necessary for protein synthesis). The number of proteins involved in the electron transfer chain is much larger than 13 or 14, but the others are coded by the nuclear DNA.
In total, the mitochondrion hosts about 3000 proteins, but only about 37 of them are coded on the mitochondrial DNA. Most of the 3000 genes are involved in a variety of processes other than ATP production, such as porphyrin synthesis. Only about 3% of them code for ATP production proteins. This means most of the genetic information coding for the protein makeup of mitochondria is in chromosomal DNA and is involved in processes other than ATP synthesis. This increases the chances that a mutation that will affect a mitochondrion will occur in chromosomal DNA, which is inherited in a Mendelian pattern. Another result is that a chromosomal mutation will affect a specific tissue due to its specific needs, whether those may be high energy requirements or a need for the catabolism or anabolism of a specific neurotransmitter or nucleic acid. Because several copies of the mitochondrial genome are carried by each mitochondrion (2-10 in humans), mitochondrial mutations can be inherited maternally by mtDNA mutations which are present in mitochondria inside the oocyte before fertilization, or (as stated above) through mutations in the chromosomes.
In humans, the heavy strand of mtDNA carries 28 genes and the light strand of mtDNA carries only 9 genes. Eight of the 9 genes on the light strand code for mitochondrial tRNA molecules. Human mtDNA consists of 16,569 nucleotide pairs. The entire molecule is regulated by only one regulatory region which contains the origins of replication of both heavy and light strands. The entire human mitochondrial DNA molecule has been mapped. The rate of mutation in mtDNA is calculated to be about ten times greater than that of nuclear DNA, possibly due to a paucity of DNA repair mechanisms. This high mutation rate leads to a high variation between mitochondria, not only among different species but even within the same species. It is calculated that if two humans are chosen randomly and their mtDNA is tested, they will have an average of between fifty and seventy different nucleotides. This may not seem like much, but when compared to the total number of nucleotides of a human mitochondrial DNA molecule (16,569), as much as .42% of the mtDNA varies between two people.

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Genetic code variants

The genetic code is, for the most part, universal, with few exceptions: mitochondrial genetics includes some of these. For most organisms the "stop codons" are “UAA”, “UAG”, and “UGA”. In vertebrate mitochondria “AGA” and “AGG” are also stop codons, but not “UGA”, which codes for tryptophan instead. “AUA” codes for isoleucine in most organisms but for methionine in vertebrate mitochondrial mRNA/tRNA.
There are many other variations among the codes used by other mitochondrial m/tRNA, which happened not to be harmful to their organisms, and which can be used as a tool (along with other mutations among the mtDNA/RNA of different species) to determine relative proximity of common ancestry of related species. (The more related two species are, the more mtDNA/RNA mutations will be the same in their mitochondrial genome).
Using these techniques, it is estimated that the first mitochondrion evolved, was consumed, or developed around 1.5 billion years ago, as an aerobic prokaryote in a symbiotic relationship within an anaerobic eukaryote.

Inheritance patterns

Because mitochondrial diseases (diseases due to malfunction of mitochondria) can be inherited both maternally and through chromosomal inheritance, the way in which they are passed on from generation to generation can vary greatly depending on the disease. Mitochondrial genetic mutations that occur in the nuclear DNA can occur in any of the chromosomes (depending on the species). Mutations inherited through the chromosomes can be autosomal dominant or recessive and can also be sex-linked dominant or recessive. Chromosomal inheritance follows normal Mendelian laws, despite the fact that the phenotype of the disease may be masked. Because of the complex ways in which mitochondrial and nuclear DNA "communicate" and interact, even seemingly simple inheritance is hard to diagnose. A mutation in chromosomal DNA may change a protein that regulates (an increase or decrease) the production of another certain protein in the mitochondria or the cytoplasm and may lead to slight, if any, noticeable symptoms. On the other hand, there are some devastating mtDNA mutations that are easy to diagnose because of their widespread damage to muscular, neural, and/or hepatic (among other high energy and metabolism dependent) tissues and because they are present in the mother and all the offspring. Mitochondrial genome mutations are passed on 100% of the time from mother to all her offspring. Because the mitochondria within the fertilized oocyte is what the new life will have to begin with (in terms of mtDNA), and because the number of affected mitochondria varies from cell (in this case, the fertilized oocyte) to cell depending both on the number it inherited from its mother cell and environmental factors which may favor mutant or wildtype mitochondrial DNA, and because the number of mtDNA molecules in the mitochondria varies from around two to ten, the number of affected mtDNA molecules inherited to a specific offspring can vary greatly. It is possible, even in twin births, for one baby to receive more than half mutant mtDNA molecules while the other twin may receive only a tiny fraction of mutant mtDNA molecules with respect to wildtype (depending on how the twins divide from each other and how many mutant mitochondria happen to be on each side of the division). In a few cases, some mitochondria or a mitochondrion from the sperm cell enters the oocyte but paternal mitochondria are actively decomposed.

Replication, repair, transcription, and translation

Mitochondrial replication is controlled by nuclear genes and is specifically suited to make as many mitochondria as that particular cell needs at the time. Human mitochondrial DNA (mtDNA) has three promoters, H1, H2, and L (heavy strand 1, heavy strand 2, and light strand promoters). The H1 promoter transcribes the entire heavy strand and the L promoter transcribes the entire light strand. The H2 promoter causes the transcription of the two mitochondrial rRNA molecules. When transcription takes place on the heavy strand a polycistronic transcript is created. The light strand produces either small transcripts, which can be used as primers, or one long transcript. The production of primers occurs by processing of light strand transcripts with the Mitochondrial RNase MRP (Mitochondrial RNA Processing). The requirement of transcription to produce primers links the process of transcription to mtDNA replication. Full length transcripts are cut into functional tRNA, rRNA, and mRNA molecules. The process of transcription initiation in mitochondria involves three types of proteins: the mitochondrial RNA polymerase (POLRMT), mitochondrial transcription factor A (TFAM), and mitochondrial transcription factors B1 and B2 (TFB1M, TFB2M). POLRMT, TFAM, and TFB1M or TFB2M assemble at the mitochondrial promoters and begin transcription. The actual molecular events that are involved in initiation are unknown, but these factors make up the basal transcription machinery and have been shown to function in vitro. Mitochondrial translation is still not very well understood. In vitro translations have still not been successful, probably due to the difficulty of isolating sufficient mt mRNA, functional mt rRNA, and possibly because of the complicated changes that the mRNA undergoes before it is translated.

Mitochondrial DNA polymerase

The Mitochondrial DNA Polymerase (Pol gamma) is used in the copying of mtDNA during replication. Because the two (heavy and light) strands on the circular mtDNA molecule have different origins of replication, it replicates in a D-loop mode. One strand begins to replicate first, displacing the other strand. This continues until replication reaches the origin of replication on the other strand, at which point the other strand beings replicating in the opposite direction. This results in two new mtDNA molecules. Each mitochondria has several copies of the mtDNA molecule and the number of mtDNA molecules is a limiting factor in mitochondrial fission. After the mitochondrion has enough mtDNA, membrane area, and membrane proteins, it can undergo fission (very similar to that which bacteria use) to become two mitochondria. Evidence suggests that mitochondria can also undergo fusion and exchange (in a form of crossover) genetic material among each other. Mitochondria sometimes form large matrices in which fusion, fission, and protein exchanges are constantly occurring. mtDNA shared among mitochondria (despite the fact that they can undergo fusion).

Damage and transcription error

Mitochondrial DNA is susceptible to damage from free oxygen radicals from mistakes that occur during the production of ATP through the electron transport chain. These mistakes can be caused by genetic disorders, cancer, and temperature variations. These radicals can damage mtDNA molecules or change them, making it hard for mitochondrial polymerase to replicate them. Both cases can lead to deletions, rearrangements, and other mutations. Recent evidence has suggested that mitochondria have enzymes that proofread mtDNA and fix mutations that may occur due to free radicals. It is believed that a DNA recombinase found in mammalian cells is also involved in a repairing recombination process. Deletions and mutations due to free radicals have been associated with the aging process. It is believed that radicals cause mutations which lead to mutant proteins, which in turn lead to more radicals. This process takes many years and is associated with some aging processes involved in oxygen-dependent tissues such as brain, heart, muscle, and kidney. Auto-enhancing processes such as these are possible causes of degenerative diseases including Parkinson’s, Alzheimer’s, and coronary artery disease.

Chromosomally mediated mtDNA replication errors

Because mitochondrial growth and fission are mediated by the nuclear DNA, mutations in nuclear DNA can have a wide array of effects on mtDNA replication. Despite the fact that the loci for some of these mutations have been found on human chromosomes, specific genes and proteins involved have not yet been isolated. Mitochondria need a certain protein to undergo fission. If this protein (made by the nucleus) is not present, the mitochondria grow but they do not divide. This leads to giant, inefficient mitochondria. Mistakes in chromosomal genes or their products can also affect mitochondrial replication more directly by inhibiting mitochondrial polymerase and can even cause mutations in the mtDNA directly and indirectly. Indirect mutations are most often caused by radicals created by defective proteins made from nuclear DNA.

Mitochondrial diseases I

Mitochondrial diseases range in severity from almost not diagnosable to fatal. They also range in cause from inherited to acquired mutations (although acquired mutations that cause disease are very rare). A certain mutation can cause several different diseases depending on the severity of the problem in the mitochondria and the tissue the affected mitochondria are in. Conversely, several different mutations may present themselves as the same disease. This almost patient-specific characterization of mitochondrial diseases makes them very hard to accurately diagnose and trace. Some diseases are observable at or even before birth (most causing death) while others do not show themselves until late adulthood. This is because the number of mutant versus wildtype mitochondria varies from cell to cell and tissue to tissue, and is always changing. Because cells have multiple mitochondria, different mitochondria in the same cell can have different variations of the mtDNA genome. This condition is referred to as heteroplasmy. When a certain tissue reaches a certain ration of mutant versus wildtype mitochondria, a disease will present itself. The ration varies from person to person and tissue to tissue (depending on its specific energy, oxygen, and metabolism requirements, and the effects of the specific mutation). Mitochondrial diseases are very numerous and different. Apart from diseases definitely caused by abnormalities in mitochondrial DNA, many diseases are suspected to be caused in part by dysfunction of mitochondria, such as diabetes mellitus, forms of cancer and cardiovascular disease, lactic acidosis, specific forms of myopathy, osteoporosis, Alzheimer's disease, Parkinsons's disease, stroke, and many more. Furthermore, mtDNA mutations are believed to play a role in the aging process.

Mitochondrial Eve

Mitochondrial Eve (mt-mrca) is the name given by researchers to the woman who is defined as the matrilineal most recent common ancestor (MRCA) for all currently living humans. Passed down from mother to offspring, her mitochondrial DNA (mtDNA) is now found in all living humans: every mtDNA in every living person is derived from hers. Mitochondrial Eve is the female counterpart of Y-chromosomal Adam, the patrilineal most recent common ancestor, although they lived at different times.
She is believed to have lived about 140,000 years ago in what is now Ethiopia, Kenya or Tanzania.The time she lived is calculated based on the molecular clock technique of correMitochondrial Evelating elapsed time with observed genetic drift.
Mitochondrial Eve is the most recent common ancestor (MRCA) of all humans via the mitochondrial DNA pathway, not the unqualified MRCA of all humanity. All living humans can trace their ancestry back to the MRCA via at least one of their parents, but Mitochondrial Eve is defined via the maternal line. Therefore, she necessarily lived at least as long, though likely much longer, ago than the MRCA of all humanity.
The existence of Mitochondrial Eve and Y-chromosomal Adam does not imply the existence of population bottlenecks or a first couple. They each lived within a large human population at a different .

Matrilineal descent

Mitochondrial Eve is the most recent common ancestor of all humans via the mitochondrial DNA pathway. In other words, she is the MRCA found when ancestry of all living humans is traced back in time, following only the maternal lineage. The mitochondrial DNA pathway is equivalent to maternal lineage, because mitochondrial DNA is only passed down from mother to child, never father to child.
To find the Mitochondrial Eve of all living humans, one can start by tracing a line from every individual to his/her mother, then continue those lines from each of those mothers to their mothers and so on, effectively tracing a family tree backward in time based purely on mitochondrial lineages. Going back through time these mitochondrial lineages will converge when two or more women have the same mother. The further back in time one goes, the fewer mitochondrial ancestors of living humans there will be. Eventually only one is left, and this one is the most recent common matrilineal ancestor of all humans alive today, i.e. Mitochondrial Eve.
It is possible to draw the same matrilineal tree forward in time by starting with all human female contemporaries of Mitochondrial Eve. Some of these women may have died childless. Others left only male children. For the rest who became mothers with at least one daughter, one can trace a line forward in time connecting them to their daughter(s). As the forward lineages progress in time, more and more lineage lines become extinct, as the last female in a line dies childless or leaves no female children. Eventually, only one single lineage remains, which includes all mothers, and in the next generation, all people, and hence all people alive today.

Mitochondrial DNA I

Mitochondrial organelles, which contain mitochondrial DNA (mtDNA), are passed only from mother to offspring. A comparison of DNA sequences from mtDNA in a population reveals a molecular phylogeny. Unlike mtDNA, which is outside the nucleus, genes containing nuclear DNA become recombined after being inherited from both parents, and therefore we can be statistically less certain about nuclear DNA origins than we can for mtDNA, which is only inherited from the mother. mtDNA also mutates at a higher rate compared to nuclear DNA, so it gives researchers a more useful, magnified view of the diversity present in a population.Just as mitochondria are inherited matrilineally, Y-chromosomes are inherited patrilineally.Thus it is possible to apply the same principles outlined above to men. The common patrilineal ancestor of all humans alive today has been dubbed Y-chromosomal Adam. Importantly, the genetic evidence suggests that the most recent patriarch of all humanity is much more recent than the most recent matriarch, suggesting that 'Adam' and 'Eve' were not alive at the same time. While 'Eve' is believed to be alive 140,000 years ago, 'Adam' lived only 60,000 years ago

Eve and the Out-of-Africa theory

Since Mitochondrial Eve is believed to have lived in Africa she is sometimes referred to as African Eve, an ancestor who has been hypothesized on the grounds of fossil as well as DNA evidence. According to the most common interpretation of the mitochondrial DNA data, the titles belong to the same hypothetical woman. Family trees (or "phylogenies") constructed on the basis of mitochondrial DNA comparisons show that the living humans whose mitochondrial lineages branched earliest from the tree are indigenous Africans, whereas the lineages of indigenous peoples on other continents all branch off from African lines. Researchers therefore reason that all living humans descend from Africans, some of whom migrated out of Africa and populated the rest of the world. If the mitochondrial analysis is correct, then because mitochondrial Eve represents the root of the mitochondrial family tree, she must have predated the exodus and lived in Africa. Therefore many researchers take the mitochondrial evidence as support for the "single-origin" or Out-of-Africa model.
Some people use the mtDNA family tree as evidence of a population bottleneck (e.g. Toba catastrophe theory) giving rise to the human species. There are, however, many ways such family trees can be constructed. A tree can be constructed based on any gene, not just the mitochondrial DNA. When different such trees including the mtDNA tree are compared, no population bottleneck is found because different trees show different coalescent points. The inconsistencies between coalescent points indicate that there had been numerous gene interchanges between population groups around the world, even after the first exodus out of Africa. This idea forms the basis of Alan Templeton's 'Out of Africa Again and Again' theory.
The Mitochondrial DNA provides another support for the Out of Africa hypothesis in the form of gene diversity. One finding not subject to interpretation is that the greatest diversity of mitochondrial DNA sequences exists among Africans. This diversity is widely believed to have accumulated because humans have been living longer in Africa than anywhere, although the same relative diversity can also be explained if just more people lived in Africa than in other regions - an interpretation of the past that all evolutionary models also accept, even those that contradict the African-origin theory, such as Multiregional evolution.

Mitochondrial genome

The mitochondrial genome is the genetic material of the mitochondria. The mitochondria are organelles that reproduce themselves semi-autonomously within eukaryotic cells.
The genetic material forming the mitochondrial genome is similar in structure to that of the prokaryotic genetic material. The mitochondrial chromosome is a circular DNA molecule, but unlike prokaryotes it is much smaller and several copies are present. This similarity supports the hypothesis that mitochondria arose from intracellular bacterial symbiotes, i.e. the endosymbiotic theory.
The mitochondria of a sexually-reproducing species are generally inherited maternally. (There are exceptions, such as among the gymnosperms, in which some families inherit mitochondria or chloroplasts paternally). In animals, mitochondrial genetic diseases can affect both males and females, but can only be transmitted by females to their offspring The human mitochondrial genome consists of 16,569 base pairs, which encodes only 13 proteins, 22 tRNAs, and 2 rRNAs.
Compared to the nuclear genome, the mitochondrial genome possesses some very interesting features:
*All the genes are carried on a single circular DNA molecule.
*The genetic material is not bounded by a nuclear envelope.
*The DNA is not packed into chromatin.
*The genome contains little non-coding DNA ("junk" DNA, or introns).
*Some codons do not follow the universal rules in translation. Instead they resemble those of purple non-sulfur bacteria.
*Some bases are considered part of two different genes: both as the last base of one gene and as the first base of the next gene.

Misconceptions

Mitochondrial Eve is the most recent common matrilineal ancestor, not the most recent common ancestor (MRCA) of all humans. The MRCA's offspring have led to all living humans via sons and daughters, but Mitochondrial Eve must be traced only through female lineages, so she is estimated to have lived much longer ago than the MRCA. While Mitochondrial Eve is thought to have been living around 140,000 years ago, according to probabilistic studies,[2] the MRCA could have been living as recently as 3,000 years ago.[3]
Allan Wilson's naming Mitochondrial Eve[4] after Eve of the Genesis creation story has led to some misunderstandings among the general public. A common misconception is that Mitochondrial Eve was the only living human female of her time. While it is theoretically possible that she was the only human female of her time; had she been the only living female of her time, humanity would most likely have become extinct due to an extreme population bottleneck.
Indeed, not only were many women alive at the same time as Mitochondrial Eve but many of them have descendants alive today. They may have left descendants via either son or daughters (and grandsons or granddaughters, and so on). Nuclear genes from these contemporary women of Mitochondrial Eve are present in today's population, but mitochondrial DNA from them is not.[1]
What distinguishes Mitochondrial Eve (and her matrilineal ancestors) from all her female contemporaries is that she has a purely matrilineal line of descent to all humans alive today, whereas all her female contemporaries with descendants alive today have at least one male in every line of descent. Because mitochondrial DNA is only passed through matrilineal descent, all humans alive today have mitochondrial DNA that is traceable back to Mitochondrial Eve.
Furthermore, it can be shown that every female contemporary of Mitochondrial Eve either has no living descendant today or is an ancestor to all living people. Starting with 'the' MRCA at around 3,000 years ago, one can trace all ancestors of the MRCA backward in time. At every ancestral generation, more and more ancestors (via both paternal and maternal lines) of MRCA are found. These ancestors are by definition also common ancestors of all living people. Eventually, there will be a point in past where all humans can be divided into two groups: those who left no descendants today and those who are common ancestors of all living humans today. This point in time is termed the identical ancestors point and is estimated to be between 5,000 and 15,000 years ago. Since Mitochondrial Eve is estimated to have lived more than hundred thousand years before the identical ancestors point, every woman contemporary to her is either not an ancestor of any living people, or a common ancestor of all living people.

Mitochondrial DNA II

Mitochondrial DNA (mtDNA) is the DNA located in organelles called mitochondria. 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 cause maternally inherited diseases and are thought to be a major contributor to aging and age-associated pathology.
In humans (and probably in metazoans in general), 100-10,000 separate copies of mtDNA are usually present per cell (egg and sperm cells are exceptions). In mammals, each circular mtDNA molecule consists of 15,000-17,000 base pairs, which encode the same 37 genes: 13 for proteins (polypeptides), 22 for transfer RNA (tRNA) and one each for the small and large subunits of ribosomal RNA (rRNA). This pattern is also seen among most metazoans, although in some cases one or more of the 37 genes is absent and the mtDNA size range is greater. Even greater variation in mtDNA gene content and size exists among fungi and plants, although there appears to be a core subset of genes that are present in all eukaryotes (except for the few that have no mitochondria at all). Some plant species have enormous mtDNAs (as many as 2,500,000 base pairs per mtDNA molecule) but, surprisingly, even those huge mtDNAs contain the same number and kinds of genes as related plants with much smaller mtDNAs.

Mitochondrial organelles, which contain mitochondrial DNA (mtDNA), are passed only from mother to offspring. A comparison of DNA sequences from mtDNA in a population reveals a molecular phylogeny. Unlike mtDNA, which is outside the nucleus, genes containing nuclear DNA become recombined after being inherited from both parents, and therefore we can be statistically less certain about nuclear DNA origins than we can for mtDNA, which is only inherited from the mother. mtDNA also mutates at a higher rate compared to nuclear DNA, so it gives researchers a more useful, magnified view of the diversity present in a population.Just as mitochondria are inherited matrilineally, Y-chromosomes are inherited patrilineally. Thus it is possible to apply the same principles outlined above to men. The common patrilineal ancestor of all humans alive today has been dubbed Y-chromosomal Adam. Importantly, the genetic evidence suggests that the most recent patriarch of all humanity is much more recent than the most recent matriarch, suggesting that 'Adam' and 'Eve' were not alive at the same time. While 'Eve' is believed to be alive 140,000 years ago, 'Adam' lived only 60,000 years ago.

Use in identification

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. Human mtDNA can be used to 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, and the like) to establish identification. mtDNA is also used to exclude possible matches between missing persons and unidentified remains. Many researchers believe that mtDNA is better suited to identification of older skeletal remains than nuclear DNA because it is often easier to harvest from older remains because of the greater number of copies of mtDNA per cell, and because a match with a living relative is possible even if numerous maternal generations separate the two. American outlaw Jesse James's remains were identified using a comparison between mtDNA extracted from his remains and the mtDNA of the son of the female-line great-granddaughter of his sister.
Because the base sequence of animal mtDNA changes rapidly, it is useful for assessing genetic relationships of individuals or groups within a species and also for identifying and quantifying the phylogeny (evolutionary relationships; see phylogenetics) among different species, provided they are not too distantly related. To do this, biologists determine and then compare the mtDNA sequences from different individuals or species. Data from the comparisons is used to construct a network of relationships among the sequences, which provides an estimate of the relationships among the individuals or species from which the mtDNAs were taken. This approach has limits that are imposed by the rate of mtDNA sequence change. In animals, the rapid rate of change makes mtDNA most useful for comparisons of individuals within species and for comparisons of species that are closely or moderately-closely related, among which the number of sequence differences can be easily counted. As the species become more distantly related, the number of sequence differences becomes very large; changes begin to accumulate on changes until an accurate count becomes impossible.

Mitochondrial inheritance I

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. 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.

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 also been reported in some insects such as the fruit fly and the honeybee.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.

Genetic influence

Genetic illness

Mutations of mitochondrial DNA can lead to a number of illnesses including exercise intolerance and Kearns-Sayre syndrome (KSS), which causes a person to lose full function of their heart, eye, and muscle movements

Mitochondrial disease II

Mitochondrial diseases are a group of disorders relating to the mitochondria, the organelles that are the "powerhouses" of the eukaryotic cells that comprise higher-order lifeforms (including humans). The mitochondria convert the energy of food molecules into the ATP that powers most cell functions.
Mitochondrial diseases comprise those disorders that in one way or another affect the function of the mitochondria and/or are due to mitochondrial DNA. 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 referred to as a mitochondrial myopathy.

Mitochondrial inheritance II

Mitochondrial inheritance behaves differently from autosomal and sex-linked inheritance. Nuclear DNA has two copies per cell (except for sperm and egg cells). One copy is inherited from the father and the other from the mother. Mitochondria, however, contain their own DNA, and contain typically from five to ten copies (see Heteroplasmy), all inherited from the mother (for more detailed inheritance patterns, see Human mitochondrial genetics). When the mitochondrion divides, the copies of DNA present are divided randomly between the two new mitochondria, and then those new mitochondria make more copies. As a result, if only a few of the DNA copies inherited from the mother are defective, mitochondrial division may cause most of the defective copies to end up in just one of the new mitochondria. Mitochondrial disease begins to become apparent once the number of affected mitochondria reaches a certain level; this phenomenon is called 'threshold expression'.
Not all of the enzymes and other components necessary for proper mitochondrial function are encoded in the mitochondrial DNA. Most mitochondrial function is controlled by nuclear DNA instead.
Mutations to mitochondrial DNA occur frequently, due to the lack of the error checking capability that nuclear DNA has. This means that mitochondrial disorders often occur spontaneously and relatively often. Sometimes the enzymes that control mitochondrial DNA duplication (and which are encoded for by genes in the nuclear DNA) are defective, causing mitochondrial DNA mutations to occur at a rapid rate.

Defects and symptoms

The effects of mitochondrial disease can be quite varied. Since the distribution of defective DNA may vary from organ to organ within the body, the mutation that in one person may cause liver disease might in another person cause a brain disorder. In addition, the severity of the defect may be great or small. Some minor defects cause only "exercise intolerance", with no serious illness or disability. Other defects can more severely affect the operation of the mitochondria and can cause severe body-wide impacts.
As a general rule, mitochondrial diseases are worst when the defective mitochondria are present in the muscles, cerebrum, or nerves, because these are the most energy-hungry cells of the body.
However, even though mitochondrial disease varies greatly in presentation from person to person, several major categories of the disease have been defined, based on the most common symptoms and the particular mutations that tend to cause them.

Types

In addition to the Mitochondrial myopathies, other examples include:
*Diabetes mellitus and deafness (DAD)
this combination at an early age can be due to mitochondrial disease
Diabetes mellitus and deafness can be found together for other reasons as well
*Leber's hereditary optic neuropathy (LHON)
*visual loss beginning in young adulthood
*Wolff-Parkinson-White syndrome
*multiple sclerosis-type disease
*Leigh syndrome, subacute sclerosing encephalopathy
after normal development the disease usually begins late in the first year of life, but the onset may occur in adulthood
a rapid decline in function occurs and is marked by seizures, altered states of consciousness, dementia, ventilatory failure
*Neuropathy, ataxia, retinitis pigmentosa, and ptosis (NARP)
progressive symptoms as described in the acronym
dementia
*Myoneurogenic gastrointestinal encephalopathy (MNGIE)
*gastrointestinal pseudo-obstruction
*neuropathy

Treatment/Pyruvic acid

Although research is ongoing, treatment options are currently limited, though vitamins are frequently prescribed.Pyruvate has been proposed recently as a treatment option.

Pyruvic acid (CH3COCO2H) is an alpha-keto acid. Pyruvate plays an important role in biochemical processes. The carboxylate anion of pyruvic acid is known as pyruvate

Chemistry

Pyruvic acid is a colorless liquid with a smell similar to that of acetic acid. It is miscible with water, and soluble in ethanol and diethyl ether. In the laboratory, pyruvic acid may be prepared by heating a mixture of tartaric acid and potassium hydrogen sulfate, by the oxidation of propylene glycol by a strong oxidizer (eg. potassium permanganate or bleach), or by the hydrolysis of acetyl cyanide, formed by reaction of acetyl chloride with potassium cyanide:
CH3COCl + KCN → CH3COCN
CH3COCN → CH3COCOOH

Biochemistry

Pyruvate is an important chemical compound in biochemistry. It is the output of the aerobic metabolism of glucose known as glycolysis. One molecule of glucose breaks down into two molecules of pyruvate, which are then used to provide further energy, in one of two ways. Pyruvate is converted into acetyl-coenzyme A, which is the main input for a series of reactions known as the Krebs cycle. Pyruvate is also converted to oxaloacetate by an anaplerotic reaction which replenishes Krebs cycle intermediates; alternatively, the oxaloacetate is used for gluconeogenesis. These reactions are named after Hans Adolf Krebs, the biochemist awarded the 1953 Nobel Prize for physiology, jointly with Fritz Lipmann, for research into metabolic processes. The cycle is also called the citric acid cycle, because citric acid is one of the intermediate compounds formed during the reactions.
If insufficient oxygen is available, the acid is broken down anaerobically, creating lactic acid in animals and ethanol in plants. Pyruvate from glycolysis is converted by anaerobic respiration to lactate using the enzyme lactate dehydrogenase and the coenzyme NADH in lactate fermentation, or to acetaldehyde and then to ethanol in alcoholic fermentation.
Pyruvate is a key intersection in the network of metabolic pathways. Pyruvate can be converted to carbohydrates via gluconeogenesis, to fatty acids or energy through acetyl-CoA, to the amino acid alanine and to ethanol. Therefore it unites several key metabolic processes.
The pyruvic acid derivative bromopyruvic acid is being studied for potential cancer treatment applications by researchers at Johns Hopkins University in ways that would support the Warburg hypothesis on the cause(s) of cancer.

Pyruvate production by glycolysis

In glycolysis, phosphoenolpyruvate (PEP) is converted to pyruvate by pyruvate kinase. This reaction is strongly exergonic and irreversible; in gluconeogenesis it takes two enzymes, pyruvate carboxylase and PEP carboxykinase to catalyze the reverse transformation of pyruvate to PEP. The arrow indicating a reverse reaction . The carboxylate anion of pyruvic acid is known as pyruvate.

Genetic influence

Genetic illness

Mutations of mitochondrial DNA can lead to a number of illnesses including exercise intolerance and Kearns-Sayre syndrome (KSS), which causes a person to lose full function of their heart, eye, and muscle movements.

Human mitochondrial DNA haplogroup

In human genetics, a human mitochondrial DNA haplogroup is a haplogroup defined by differences in human mitochondrial DNA. These haplogroups have led some researchers to trace the matrilineal inheritance of modern humans back to human origins in Africa and the subsequent spread across the globe.
Known haplogroups are assigned the following letter codes: A, B, C, CZ, D, E, F, G, H, pre-HV, HV, I, J, pre-JT, JT, K, L0, L1, L2, L3, L4, L5, L6, L7, M, N, P, Q, R, S, T, U, UK, V, W, X, Y, and Z.
The woman at the root of all these groups was the most recent common matrilineal (female-lineage) ancestor of all living humans. She is commonly called Mitochondrial Eve.

Cambridge Reference Sequence

The Cambridge Reference Sequence (CRS) for human mitochondrial DNA was first published in 1981 leading to the initiation of the human genome project. A group under Dr. Fred Sanger at Cambridge University sequenced the mitochondrial genome of one individual of European descent during the 1970s, determining it to have a length of about 16,568 base pairs (0.0006% of the total human genome) containing some 37 genes.
When the sequencing was repeated by other researchers, it was noted that there were some striking discrepancies. On further replication, it was determined that the original publication had included some eleven errors of sequencing, including one "extra" base pair in position 3,107, and occasional incorrect assignments of single base pairs. Some of these were the result of contamination with bovine and HeLa specimens. The revised CRS mtDNA was published by Richard Andrews in 1999. (The original nucleotide numbering was retained to avoid confusion.) The reference sequence belongs to European haplogroup H.
When mitochondrial DNA testing is used for genealogical purposes, the results are usually reported as "differences" from the revised CRS. Such differences are not necessarily mutations: the CRS is a reference sequence rather than a record of the earliest human mtDNA