视频: 线粒体DNA的遗传Inheritances of mitochondrial DNA
线粒体DNA（英语：Mitochondrial DNA，缩写mtDNA）是指一些位于线粒体内的DNA，与一般位于细胞核内的DNA有不同的演化起源，可能是源自早期细菌。虽然现存生物体中绝大多数作用于线粒体的蛋白质，是由细胞核DNA所制造，但这些基因中有一些可能是源于细菌，并于演化过程中转移到细胞核中。
现今人类体内的每个细胞中，大约有1000到10000个线粒体，而每一个线粒体内，则大约有2到10组mtDNA，每个mtDNA共包含16569个碱基对，其中有37个基因，可用来制造13种蛋白质、22种tRNA与两种rRNA。其中的内含子较细胞核基因少，且有些不含内含子，如tRNA基因。
突变速率
动物体内的线粒体DNA并不会经过遗传重组，因此与细胞核DNA相较之下有较高的突变速率（重组有修复突变的功能）；而植物与真菌类体内的mtDNA则存在着重组现象，其中植物的mtDNA突变速率高于细胞核DNA；真菌方面的mtDNA突变速率则尚未明了[1]。
由于动物的mtDNA的突变速率高于细胞核DNA，较为容易测量计算，使mtDNA成为用来追溯动物母系族谱的有效工具，例如许多物种在数百个世代以前的祖先。此外，人类的mtDNA也可用来进行个体辨识。
线粒体DNA起源
内共生理论认为真核细胞最早的起源，是因为原核细胞（细菌等）被吸收到另外一个细胞中，而没有被消化。而这两个细胞之后产生了共生关系，使最早的细胞器诞生，此胞器后来成为现今的线粒体，其基因组也在演化过程中转变成线粒体DNA。
线粒体遗传
对动物而言，受精卵中的mtDNA主要遗传自母亲；而对植物来说略有变异，但仍然以母系遗传为主；真菌则源自双亲。
雌性遗传
正常状况下，线粒体只会遗传自母亲，以哺乳类而言，一般在受精之后，卵子细胞就会将精子中的线粒体摧毁。1999年发表的研究中显示，父系精子线粒体（含有mtDNA）带有泛素（ubiquitin）标记，因而在胚胎中会被挑选出来，进而遭到摧毁[2]。不过某些细胞外的人工受精技术可直接将精子注入卵子细胞内，可能会干扰摧毁精子线粒体的过程。
由于母系遗传的特性，使得研究者能够借由线粒体DNA，追溯长时间的母系族谱（与之相对的为专门用来追溯父系族谱的Y染色体）。人类的线粒体DNA中累积了一些高度变异控制区域（hypervariable control region；包括HVR1与HVR2），在HVR1中含有大约440个碱基对，这些碱基对可用来与其他个体（特定人士或数据库中的讯息）的控制区作比对，进而测定出母系族谱。Vilà等人的研究中回溯了家犬与狼的母系祖先，同样的分析方式也导出了线粒体夏娃概念，用于研究人类起源。
由于mtDNA并非高度保守，而是拥有较快的突变速率，因此可用来研究系统发生学，生物学家挑选少量不同物种的基因，分析其序列的保留与变异程度，可建立出演化树。
雄性遗传
目前已知有时候有些物种体内，如蚌类，也会有一些遗传自父亲的线粒体[3]。此外，也有研究发现某些昆虫，如果蝇[4]与蜜蜂[5]，也有父系线粒体遗传的现象。
少量的例证显示雄性线粒体遗传也存在于某些哺乳类。曾有人发表老鼠的父系线粒体遗传[6][7]，但随后又遭否定。此外，已知具父系线粒体遗传的还有绵羊[8]与复制牛[9]。某些人类个案中，也发现同样情形[10]，这种情形相当少见，整个线粒体中可能只有一个线粒体DNA是遗传自父亲[11]。
遗传疾病
线粒体DNA的突变可造成许多的疾病，如运动障碍（exercise intolerance）或凯塞综合征（Kearns-Sayre syndrome，KSS），一种可使患者心脏、眼睛与肌肉完全失去运动功能的疾病。
A 3-D animation of the way that a zygote receives nuclear, or genomic, DNA from both parents (sperm and egg cells) but inherits mitochondrial DNA only from the mother. It is so, because female's ovum has mitochondria, but spermatozoon do not.
Mitochondrial DNA (mtDNA or mDNA[2]) is the DNA located in organelles called mitochondria, structures within eukaryotic cells that convert chemical energy from food into a form that cells can use, adenosine triphosphate (ATP). Nearly all of the DNA present in eukaryotic cells can be found in the cell nucleus, and in plants, the chloroplast as well.
In humans, mitochondrial DNA can be assessed as the smallest chromosome coding for only 37 genes and containing only about 16,600 base pairs. Human mitochondrial DNA was the first significant part of the human genome to be sequenced. In most species, including humans, mtDNA is inherited solely from the mother.[3]
The DNA sequence of mtDNA has been determined from a large number of organisms and individuals (including some organisms that are extinct), and the comparison of those DNA sequences represents a mainstay of phylogenetics, in that it allows biologists to elucidate the evolutionary relationships among species. It also permits an examination of the relatedness of populations, and so has become important in anthropology and field biology
Origin[edit]
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.[4] 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.
Mitochondrial inheritance[edit]
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.
Female inheritance[edit]
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.[5] 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 trace the agnate lineage.) This is accomplished on human mitochondrial DNA by sequencing one or more of the hypervariable control regions (HVR1 or HVR2) of the mitochondrial DNA, as with a genealogical DNA test. 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.[6] 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.
As 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[edit]
Main article: Paternal mtDNA transmission
It has been reported that mitochondria can occasionally be inherited from the father in some species such as mussels.[7][8] Paternally inherited mitochondria have additionally been reported in some insects such as fruit flies,[9] honeybees,[10] and periodical cicadas.[11]
Evidence supports rare instances of male mitochondrial inheritance in some mammals as well. Specifically, documented occurrences exist for mice,[12][13] where the male-inherited mitochondria was subsequently rejected. It has also been found in sheep,[14] and in cloned cattle.[15] It has been found in a single case in a human male.[16]
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.
Structure[edit]
In most multicellular organisms, the mtDNA is organized as a circular, covalently closed, double-stranded DNA. But in many unicellular (e.g. the ciliate Tetrahymena or 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, as many of these unicellular organisms with linear mtDNA are known pathogens.[17]
For human mitochondrial DNA (and probably for that of 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[18] base pairs. The two strands of mtDNA are differentiated by their nucleotide content with the guanine-rich strand referred to as the heavy strand (or H-strand), and the cytosine-rich strand referred to as the light strand (or L-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.[19]
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.[20]
Replication[edit]
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 a 55 kDa accessory subunit encoded by the POLG2 gene.[21] 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.[22]
During embryogenesis, replication of mtDNA is strictly down-regulated from the fertilized oocyte through the preimplantation embryo.[21] At the blastocyst stage, the onset of mtDNA replication is specific to the cells of the trophectoderm.[21] In contrast, the cells of the inner cell mass restrict mtDNA replication until they receive the signals to differentiate to specific cell types.[21]
Mutations[edit]
The involvement of mitochondrial DNA in several human diseases.
Susceptibility[edit]
mtDNA is particularly susceptible to reactive oxygen species generated by the respiratory chain due to its 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 are therefore thought to contribute to enhanced susceptibility of mtDNA to oxidative damage. The outcome of mutation in mtDNA may be alteration in the coding instructions for some proteins,[23] which may have an effect on organism metabolism and/or fitness.
Genetic illness[edit]
Further information: Mitochondrial disease
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.[24]
Use in disease diagnosis[edit]
Recently a mutation in mtDNA has been used to help diagnose prostate cancer in patients with negative prostate biopsy.[25][26]
Relationship with aging[edit]
Though the idea is controversial, some evidence suggests a link between aging and mitochondrial genome dysfunction.[27] 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). There is thought to be a positive feedback loop at work; 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.[28] Supporting such a link between longevity and mitochondrial DNA, some studies have found correlations between biochemical properties of the mitochondrial DNA and the longevity of species.[29] 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.[30][31]
Use in identification[edit]
For use in human identification, see Human mitochondrial DNA.
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,[32] 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 low effective population size and rapid mutation rate (in animals) makes mtDNA useful for assessing genetic relationships of individuals or groups within a species and also for identifying and quantifying the phylogeny (evolutionary relationships; see phylogenetics) among different species, provided they are not too distantly related. To do this, biologists determine and then compare the mtDNA sequences from different individuals or species. Data from the comparisons is used to construct a network of relationships among the sequences, which provides an estimate of the relationships among the individuals or species from which the mtDNAs were taken. This approach has limits that are imposed by the rate of mtDNA sequence change. In animals, the high mutation rate 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 DNA was admitted into evidence for the first time ever in 1996 during State of Tennessee v. Paul Ware.[33]
Mitochondrial DNA was first admitted into evidence in California in the successful prosecution of David Westerfield for the 2002 murder of 7-year-old Danielle van Dam in San Diego: it was used for both human and dog identification.[34][35]
History[edit]
Mitochondrial DNA was discovered in the 1960s by Margit M. K. Nass and Sylvan Nass by electron microscopy as DNase-sensitive thread inside mitochondria,[36] and by Ellen Haslbrunner, Hans Tuppy and Gottfried Schatz by biochemical assays on highly purified mitochondrial fractions.[37]
原文链接：http://www.bioku.net/archives/4994
现今人类体内的每个细胞中，大约有1000到10000个线粒体，而每一个线粒体内，则大约有2到10组mtDNA，每个mtDNA共包含16569个碱基对，其中有37个基因，可用来制造13种蛋白质、22种tRNA与两种rRNA。其中的内含子较细胞核基因少，且有些不含内含子，如tRNA基因。
突变速率
动物体内的线粒体DNA并不会经过遗传重组，因此与细胞核DNA相较之下有较高的突变速率（重组有修复突变的功能）；而植物与真菌类体内的mtDNA则存在着重组现象，其中植物的mtDNA突变速率高于细胞核DNA；真菌方面的mtDNA突变速率则尚未明了[1]。
由于动物的mtDNA的突变速率高于细胞核DNA，较为容易测量计算，使mtDNA成为用来追溯动物母系族谱的有效工具，例如许多物种在数百个世代以前的祖先。此外，人类的mtDNA也可用来进行个体辨识。
线粒体DNA起源
内共生理论认为真核细胞最早的起源，是因为原核细胞（细菌等）被吸收到另外一个细胞中，而没有被消化。而这两个细胞之后产生了共生关系，使最早的细胞器诞生，此胞器后来成为现今的线粒体，其基因组也在演化过程中转变成线粒体DNA。
线粒体遗传
对动物而言，受精卵中的mtDNA主要遗传自母亲；而对植物来说略有变异，但仍然以母系遗传为主；真菌则源自双亲。
雌性遗传
正常状况下，线粒体只会遗传自母亲，以哺乳类而言，一般在受精之后，卵子细胞就会将精子中的线粒体摧毁。1999年发表的研究中显示，父系精子线粒体（含有mtDNA）带有泛素（ubiquitin）标记，因而在胚胎中会被挑选出来，进而遭到摧毁[2]。不过某些细胞外的人工受精技术可直接将精子注入卵子细胞内，可能会干扰摧毁精子线粒体的过程。
由于母系遗传的特性，使得研究者能够借由线粒体DNA，追溯长时间的母系族谱（与之相对的为专门用来追溯父系族谱的Y染色体）。人类的线粒体DNA中累积了一些高度变异控制区域（hypervariable control region；包括HVR1与HVR2），在HVR1中含有大约440个碱基对，这些碱基对可用来与其他个体（特定人士或数据库中的讯息）的控制区作比对，进而测定出母系族谱。Vilà等人的研究中回溯了家犬与狼的母系祖先，同样的分析方式也导出了线粒体夏娃概念，用于研究人类起源。
由于mtDNA并非高度保守，而是拥有较快的突变速率，因此可用来研究系统发生学，生物学家挑选少量不同物种的基因，分析其序列的保留与变异程度，可建立出演化树。
雄性遗传
目前已知有时候有些物种体内，如蚌类，也会有一些遗传自父亲的线粒体[3]。此外，也有研究发现某些昆虫，如果蝇[4]与蜜蜂[5]，也有父系线粒体遗传的现象。
少量的例证显示雄性线粒体遗传也存在于某些哺乳类。曾有人发表老鼠的父系线粒体遗传[6][7]，但随后又遭否定。此外，已知具父系线粒体遗传的还有绵羊[8]与复制牛[9]。某些人类个案中，也发现同样情形[10]，这种情形相当少见，整个线粒体中可能只有一个线粒体DNA是遗传自父亲[11]。
遗传疾病
线粒体DNA的突变可造成许多的疾病，如运动障碍（exercise intolerance）或凯塞综合征（Kearns-Sayre syndrome，KSS），一种可使患者心脏、眼睛与肌肉完全失去运动功能的疾病。
A 3-D animation of the way that a zygote receives nuclear, or genomic, DNA from both parents (sperm and egg cells) but inherits mitochondrial DNA only from the mother. It is so, because female's ovum has mitochondria, but spermatozoon do not.
Mitochondrial DNA (mtDNA or mDNA[2]) is the DNA located in organelles called mitochondria, structures within eukaryotic cells that convert chemical energy from food into a form that cells can use, adenosine triphosphate (ATP). Nearly all of the DNA present in eukaryotic cells can be found in the cell nucleus, and in plants, the chloroplast as well.
In humans, mitochondrial DNA can be assessed as the smallest chromosome coding for only 37 genes and containing only about 16,600 base pairs. Human mitochondrial DNA was the first significant part of the human genome to be sequenced. In most species, including humans, mtDNA is inherited solely from the mother.[3]
The DNA sequence of mtDNA has been determined from a large number of organisms and individuals (including some organisms that are extinct), and the comparison of those DNA sequences represents a mainstay of phylogenetics, in that it allows biologists to elucidate the evolutionary relationships among species. It also permits an examination of the relatedness of populations, and so has become important in anthropology and field biology
Origin[edit]
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.[4] 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.
Mitochondrial inheritance[edit]
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.
Female inheritance[edit]
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.[5] 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 trace the agnate lineage.) This is accomplished on human mitochondrial DNA by sequencing one or more of the hypervariable control regions (HVR1 or HVR2) of the mitochondrial DNA, as with a genealogical DNA test. 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.[6] 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.
As 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[edit]
Main article: Paternal mtDNA transmission
It has been reported that mitochondria can occasionally be inherited from the father in some species such as mussels.[7][8] Paternally inherited mitochondria have additionally been reported in some insects such as fruit flies,[9] honeybees,[10] and periodical cicadas.[11]
Evidence supports rare instances of male mitochondrial inheritance in some mammals as well. Specifically, documented occurrences exist for mice,[12][13] where the male-inherited mitochondria was subsequently rejected. It has also been found in sheep,[14] and in cloned cattle.[15] It has been found in a single case in a human male.[16]
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.
Structure[edit]
In most multicellular organisms, the mtDNA is organized as a circular, covalently closed, double-stranded DNA. But in many unicellular (e.g. the ciliate Tetrahymena or 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, as many of these unicellular organisms with linear mtDNA are known pathogens.[17]
For human mitochondrial DNA (and probably for that of 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[18] base pairs. The two strands of mtDNA are differentiated by their nucleotide content with the guanine-rich strand referred to as the heavy strand (or H-strand), and the cytosine-rich strand referred to as the light strand (or L-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.[19]
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.[20]
Replication[edit]
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 a 55 kDa accessory subunit encoded by the POLG2 gene.[21] 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.[22]
During embryogenesis, replication of mtDNA is strictly down-regulated from the fertilized oocyte through the preimplantation embryo.[21] At the blastocyst stage, the onset of mtDNA replication is specific to the cells of the trophectoderm.[21] In contrast, the cells of the inner cell mass restrict mtDNA replication until they receive the signals to differentiate to specific cell types.[21]
Mutations[edit]
The involvement of mitochondrial DNA in several human diseases.
Susceptibility[edit]
mtDNA is particularly susceptible to reactive oxygen species generated by the respiratory chain due to its 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 are therefore thought to contribute to enhanced susceptibility of mtDNA to oxidative damage. The outcome of mutation in mtDNA may be alteration in the coding instructions for some proteins,[23] which may have an effect on organism metabolism and/or fitness.
Genetic illness[edit]
Further information: Mitochondrial disease
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.[24]
Use in disease diagnosis[edit]
Recently a mutation in mtDNA has been used to help diagnose prostate cancer in patients with negative prostate biopsy.[25][26]
Relationship with aging[edit]
Though the idea is controversial, some evidence suggests a link between aging and mitochondrial genome dysfunction.[27] 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). There is thought to be a positive feedback loop at work; 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.[28] Supporting such a link between longevity and mitochondrial DNA, some studies have found correlations between biochemical properties of the mitochondrial DNA and the longevity of species.[29] 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.[30][31]
Use in identification[edit]
For use in human identification, see Human mitochondrial DNA.
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,[32] 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 low effective population size and rapid mutation rate (in animals) makes mtDNA useful for assessing genetic relationships of individuals or groups within a species and also for identifying and quantifying the phylogeny (evolutionary relationships; see phylogenetics) among different species, provided they are not too distantly related. To do this, biologists determine and then compare the mtDNA sequences from different individuals or species. Data from the comparisons is used to construct a network of relationships among the sequences, which provides an estimate of the relationships among the individuals or species from which the mtDNAs were taken. This approach has limits that are imposed by the rate of mtDNA sequence change. In animals, the high mutation rate 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 DNA was admitted into evidence for the first time ever in 1996 during State of Tennessee v. Paul Ware.[33]
Mitochondrial DNA was first admitted into evidence in California in the successful prosecution of David Westerfield for the 2002 murder of 7-year-old Danielle van Dam in San Diego: it was used for both human and dog identification.[34][35]
History[edit]
Mitochondrial DNA was discovered in the 1960s by Margit M. K. Nass and Sylvan Nass by electron microscopy as DNase-sensitive thread inside mitochondria,[36] and by Ellen Haslbrunner, Hans Tuppy and Gottfried Schatz by biochemical assays on highly purified mitochondrial fractions.[37]
原文链接：http://www.bioku.net/archives/4994
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helu 赞了这篇日记 2024-02-20 16:36:47
