In genetics, paternal mtDNA transmission and paternal mtDNA inheritance refer to the incidence of mitochondrial DNA (mtDNA) being passed from a father to his offspring. Paternal mtDNA inheritance is observed in a small proportion of species; in general, mtDNA is passed unchanged from a mother to her offspring, [1] making it an example of non-Mendelian inheritance. In contrast, mtDNA transmission from both parents occurs regularly in certain bivalves.
Paternal mtDNA inheritance in animals varies. For example, in Mytilidae mussels, paternal mtDNA "is transmitted through the sperm and establishes itself only in the male gonad." [2] [3] [4] In testing 172 sheep, "The Mitochondrial DNA from three lambs in two half-sib families were found to show paternal inheritance." [5] An instance of paternal leakage resulted in a study on chickens. [6] There has been evidences that paternal leakage is an integral part of mitochondrial inheritance of Drosophila simulans . [7]
In human mitochondrial genetics, there is debate over whether or not paternal mtDNA transmission is possible. Many studies hold that paternal mtDNA is never transmitted to offspring. [8] This thought is central to mtDNA genealogical DNA testing and to the theory of mitochondrial Eve. 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.
Since the father's mtDNA is located in the sperm midpiece (the mitochondrial sheath), which is lost at fertilization, all children of the same mother are hemizygous for maternal mtDNA and are thus identical to each other and to their mother. Because of its cytoplasmic location in eukaryotes, mtDNA does not undergo meiosis and there is normally no crossing-over, hence there is no opportunity for introgression of the father's mtDNA. All mtDNA is thus inherited maternally; mtDNA has been used to infer the pedigree of the well-known "mitochondrial Eve." [9]
In sexual reproduction, paternal mitochondria found in the sperm are actively decomposed, thus preventing "paternal leakage". Mitochondria in mammalian sperm are usually destroyed by the egg cell after 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. [10] Some in vitro fertilization (IVF) techniques, particularly intracytoplasmic sperm injection (ICSI) of a sperm into an oocyte, may interfere with this.
It is now understood that the tail of the sperm, which contains additional mtDNA, may also enter the egg. This had led to increased controversy about the fate of paternal mtDNA.
Over the last 5 years, there has been considerable debate as to whether there is recombination in human mitochondrial DNA (mtDNA) (for references, see Piganeau and Eyre-Walker, 2004). That debate appears to have finally come to an end with the publication of some direct evidence of recombination. Schwartz and Vissing (2002) presented the case of a 28-year-old man who had both maternal and paternally derived mtDNA in his muscle tissue – in all his other tissues he had only maternally derived mtDNA. It was the first time that paternal leakage and, consequently, heteroplasmy was observed in human mtDNA. In a recent paper, Kraytsberg et al (2004) take this observation one step further, and claim to show that there has been recombination between the maternal and paternal mtDNA in this individual. [11]
Some sources state that so little paternal mtDNA is transmitted as to be negligible ("At most, one presumes it must be less than 1 in 1000, since there are 100 000 mitochondria in the human egg and only 100 in the sperm (Satoh and Kuroiwa, 1991)." [11] ) or that paternal mtDNA is so rarely transmitted as to be negligible ("Nevertheless, studies have established that paternal mtDNA is so rarely transmitted to offspring that mtDNA analyses remain valid..." [12] ). A few studies indicate that, very rarely, a small portion of a person's mitochondria can be inherited from the father. [13] [14]
The controversy about human paternal leakage was summed up in the 1996 study Misconceptions about mitochondria and mammalian fertilization: Implications for theories on human evolution, which was peer-reviewed and printed in Proceedings of the National Academy of Sciences. [15] According to the study's abstract:
In vertebrates, inheritance of mitochondria is thought to be predominantly maternal, and mitochondrial DNA analysis has become a standard taxonomic tool. In accordance with the prevailing view of strict maternal inheritance, many sources assert that during fertilization, the sperm tail, with its mitochondria, gets excluded from the embryo. This is incorrect. In the majority of mammals—including humans—the midpiece mitochondria can be identified in the embryo even though their ultimate fate is unknown. The "missing mitochondria" story seems to have survived—and proliferated—unchallenged in a time of contention between hypotheses of human origins, because it supports the "African Eve" model of recent radiation of Homo sapiens out of Africa.
The mixing of maternal and paternal mtDNA was thought to have been found in chimpanzees in 1999 [16] and in humans in 1999 [17] and 2018. This last finding is significant, as biparental mtDNA was observed in subsequent generations in three different families leading to the conclusion that, although the maternal transmission dogma remains strong, there is evidence that paternal transmission does exist and there is a probably a mechanism which, if elucidated, can be a new tool in the reproductive field (e.g. avoiding mitochondrial replacement therapy, and just using this mechanism so that the offspring inherit the paternal mitochondria). [18] However, there has been only a single documented case among humans in which as much as 90% of a single tissue type's mitochondria was inherited through paternal transmission. [19]
According to the 2005 study More evidence for non-maternal inheritance of mitochondrial DNA?, [20] heteroplasmy is a "newly discovered form of inheritance for mtDNA. Heteroplasmy introduces slight statistical uncertainty in normal inheritance patterns." [21] Heteroplasmy may result from a mutation during development which is propagated to only a subset of the adult cells, or may occur when two slightly different mitochondrial sequences are inherited from the mother as a result of several hundred mitochondria being present in the ovum. However, the 2005 study states: [20]
Multiple types (or recombinant types) of quite dissimilar mitochondrial DNA from different parts of the known mtDNA phylogeny are often reported in single individuals. From re-analyses and corrigenda of forensic mtDNA data, it is apparent that the phenomenon of mosaic or mixed mtDNA can be ascribed solely to contamination and sample mix up.
A study published in PNAS in 2018 titled Biparental Inheritance of Mitochondrial DNA in Humans found paternal mtDNA (ranging from 24 to 76%) in 17 individuals from three unrelated multigeneration families known to have a high level of mtDNA heteroplasmy: [22]
A comprehensive exploration of mtDNA segregation in these families shows biparental mtDNA transmission with an autosomal dominantlike inheritance mode. Our results suggest that, although the central dogma of maternal inheritance of mtDNA remains valid, there are some exceptional cases where paternal mtDNA could be passed to the offspring.
Some organisms, such as Cryptosporidium , have mitochondria with no DNA whatsoever. [23]
In plants, it has also been reported that mitochondria can occasionally be inherited from the father, e.g. in bananas. Some Conifers also show paternal inheritance of mitochondria, such as the coast redwood, Sequoia sempervirens .
A mitochondrion (pl. mitochondria) is an organelle found in the cells of most eukaryotes, such as animals, plants and fungi. Mitochondria have a double membrane structure and use aerobic respiration to generate adenosine triphosphate (ATP), which is used throughout the cell as a source of chemical energy. They were discovered by Albert von Kölliker in 1857 in the voluntary muscles of insects. Meaning a thread-like granule, the term mitochondrion was coined by Carl Benda in 1898. The mitochondrion is popularly nicknamed the "powerhouse of the cell", a phrase popularized by Philip Siekevitz in a 1957 Scientific American article of the same name.
A zygote is a eukaryotic cell formed by a fertilization event between two gametes. The zygote's genome is a combination of the DNA in each gamete, and contains all of the genetic information of a new individual organism. The sexual fusion of haploid cells is called karyogamy, the result of which is the formation of a diploid cell called the zygote or zygospore.
Selfish genetic elements are genetic segments that can enhance their own transmission at the expense of other genes in the genome, even if this has no positive or a net negative effect on organismal fitness. Genomes have traditionally been viewed as cohesive units, with genes acting together to improve the fitness of the organism.
Mitochondrial DNA is the DNA located in the mitochondria organelles in a eukaryotic cell that converts chemical energy from food into adenosine triphosphate (ATP). Mitochondrial DNA is a small portion of the DNA contained in a eukaryotic cell; most of the DNA is in the cell nucleus, and, in plants and algae, the DNA also is found in plastids, such as chloroplasts.
Mitochondrial disease is a group of disorders caused by mitochondrial dysfunction. Mitochondria are the organelles that generate energy for the cell and are found in every cell of the human body except red blood cells. They convert the energy of food molecules into the ATP that powers most cell functions.
An oocyte, oöcyte, or ovocyte is a female gametocyte or germ cell involved in reproduction. In other words, it is an immature ovum, or egg cell. An oocyte is produced in a female fetus in the ovary during female gametogenesis. The female germ cells produce a primordial germ cell (PGC), which then undergoes mitosis, forming oogonia. During oogenesis, the oogonia become primary oocytes. An oocyte is a form of genetic material that can be collected for cryoconservation.
Heteroplasmy is the presence of more than one type of organellar genome within a cell or individual. It is an important factor in considering the severity of mitochondrial diseases. Because most eukaryotic cells contain many hundreds of mitochondria with hundreds of copies of mitochondrial DNA, it is common for mutations to affect only some mitochondria, leaving most unaffected.
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. It has been discovered, though, that homoplasmic mitochondrial DNA mutations may be found in human tumors.
Human mitochondrial genetics is the study of the genetics of human mitochondrial DNA. The human mitochondrial genome is the entirety of hereditary information contained in human mitochondria. Mitochondria are small structures in cells that generate energy for the cell to use, and are hence referred to as the "powerhouses" of the cell.
Non-Mendelian inheritance is any pattern in which traits do not segregate in accordance with Mendel's laws. These laws describe the inheritance of traits linked to single genes on chromosomes in the nucleus. In Mendelian inheritance, each parent contributes one of two possible alleles for a trait. If the genotypes of both parents in a genetic cross are known, Mendel's laws can be used to determine the distribution of phenotypes expected for the population of offspring. There are several situations in which the proportions of phenotypes observed in the progeny do not match the predicted values.
Sperm is the male reproductive cell, or gamete, in anisogamous forms of sexual reproduction. Animals produce motile sperm with a tail known as a flagellum, which are known as spermatozoa, while some red algae and fungi produce non-motile sperm cells, known as spermatia. Flowering plants contain non-motile sperm inside pollen, while some more basal plants like ferns and some gymnosperms have motile sperm.
MELAS is one of the family of mitochondrial diseases, which also include MIDD, MERRF syndrome, and Leber's hereditary optic neuropathy. It was first characterized under this name in 1984. A feature of these diseases is that they are caused by defects in the mitochondrial genome which is inherited purely from the female parent. The most common MELAS mutation is mitochondrial mutation, mtDNA, referred to as m.3243A>G.
Extranuclear inheritance or cytoplasmic inheritance is the transmission of genes that occur outside the nucleus. It is found in most eukaryotes and is commonly known to occur in cytoplasmic organelles such as mitochondria and chloroplasts or from cellular parasites like viruses or bacteria.
Neuropathy, ataxia, and retinitis pigmentosa, also known as NARP syndrome, is a rare disease with mitochondrial inheritance that causes a variety of signs and symptoms chiefly affecting the nervous system Beginning in childhood or early adulthood, most people with NARP experience numbness, tingling, or pain in the arms and legs ; muscle weakness; and problems with balance and coordination (ataxia). Many affected individuals also have vision loss caused by changes in the light-sensitive tissue that lines the back of the eye. In some cases, the vision loss results from a condition called retinitis pigmentosa. This eye disease causes the light-sensing cells of the retina gradually to deteriorate.
Organellar DNA (oDNA) is DNA contained in organelles (such as mitochondria and chloroplasts), outside the nucleus of eukaryotic cells.
Uniparental inheritance is a non-Mendelian form of inheritance that consists of the transmission of genotypes from one parental type to all progeny. That is, all the genes in offspring will originate from only the mother or only the father. This phenomenon is most commonly observed in eukaryotic organelles such as mitochondria and chloroplasts. This is because such organelles contain their own DNA and are capable of independent mitotic replication that does not endure crossing over with the DNA from another parental type. Although uniparental inheritance is the most common form of inheritance in organelles, there is increased evidence of diversity. Some studies found doubly uniparental inheritance (DUI) and biparental transmission to exist in cells. Evidence suggests that even when there is biparental inheritance, crossing-over doesn't always occur. Furthermore, there is evidence that the form of organelle inheritance varied frequently over time. Uniparental inheritance can be divided into multiple subtypes based on the pathway of inheritance.
Mitochondrial replacement therapy (MRT), sometimes called mitochondrial donation, is the replacement of mitochondria in one or more cells to prevent or ameliorate disease. MRT originated as a special form of in vitro fertilisation in which some or all of the future baby's mitochondrial DNA (mtDNA) comes from a third party. This technique is used in cases when mothers carry genes for mitochondrial diseases. The therapy is approved for use in the United Kingdom. A second application is to use autologous mitochondria to replace mitochondria in damaged tissue to restore the tissue to a functional state. This has been used in clinical research in the United States to treat cardiac-compromised newborns.
In biology, mother's curse is an evolutionary effect that males inherit deleterious mitochondrial genome (mtDNA) mutations from their mother, while those mutations are beneficial, neutral or less deleterious to females.
Taosheng Huang is a physician-scientist with substantial academic achievements and professional experience in translational research, specifically, in human mitochondrial genetics. He is a full Professor and Director of the Molecular Diagnostic Laboratory in the Division of Human Genetics at Cincinnati Children’s Hospital Medical Center (CCHMC). Huang has published over 100 manuscripts in many impactful journals.
Biparental inheritance is a type of biological inheritance where the progeny inherits a maternal and a paternal allele for one gene. It is one of the criteria for Mendelian inheritance. Sexual reproduction, where offspring result from the fusion of gametes from two parents, is the most common form of biparental inheritance. While less common, cases of biparental inheritance in extranuclear genes have been documented, such as biparental inheritance of mitochondrial DNA, or chloroplast DNA in plants. Biparental inheritance of nuclear DNA by way of sexual reproduction can allow for new combinations of alleles from each contributing parent. The production of gametes through meiosis can sometimes include recombination, or crossing-over, which is a possibility for novel combinations of alleles.
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