Mitochondria have their own DNA. Mitochondrial DNA. Comparison of mitochondrial DNA of Neanderthals and modern humans

Historically, the first study of this kind was carried out using mitochondrial DNA. Scientists took a sample from the natives of Africa, Asia, Europe, America, and in this, initially small, sample compared the mitochondrial DNA of different individuals with each other. They found that mitochondrial DNA diversity is highest in Africa. And since it is known that mutational events can change the type of mitochondrial DNA, and it is also known how it can change, then, therefore, it is possible to say which types of people could mutate from which. Of all the people who were DNA tested, it was the Africans who found much greater variability. Mitochondrial DNA types on other continents were less diverse. This means Africans have had more time to accumulate these changes. They had more time for biological evolution, if it is in Africa that ancient DNA remnants are found that are not characteristic of European human mutations.

It can be argued that geneticists using mitochondrial DNA managed to prove the origin of women in Africa. They also studied Y chromosomes. It turned out that men also come from Africa.

Thanks to studies of mitochondrial DNA, it is possible to establish not only that a person originated from Africa, but also to determine the time of his origin. The time of the appearance of the mitochondrial foremother of mankind was established through a comparative study of the mitochondrial DNA of chimpanzees and modern humans. Knowing the rate of mutational divergence - 2-4% per million years - it is possible to determine the time of separation of the two branches, chimpanzee and modern man. This happened about 5 - 7 million years ago. The rate of mutational divergence is assumed to be constant.

Mitochondrial Eve

When people talk about mitochondrial Eve, they don't mean the individual. They talk about the emergence by evolution of an entire population of individuals with similar characteristics. It is believed that mitochondrial Eve lived during a period of sharp decline in the number of our ancestors, to about ten thousand individuals.

Origin of races

Studying the mitochondrial DNA of different populations, geneticists suggested that even before leaving Africa, the ancestral population was divided into three groups, which gave rise to three modern races - African, Caucasoid and Mongoloid. It is believed that this happened approximately 60 - 70 thousand years ago.

Comparison of mitochondrial DNA of Neanderthals and modern humans

Additional information about the origin of man was obtained by comparing the genetic texts of the mitochondrial DNA of the Neanderthal and modern humans. Scientists were able to read the genetic texts of the mitochondrial DNA of the bone remains of two Neanderthals. The bones of the first Neanderthal were found in the Feldhover Cave in Germany. A little later, the genetic text of the mitochondrial DNA of a Neanderthal child was read, which was found in the North Caucasus in the Mezhmayskaya cave. When comparing the mitochondrial DNA of modern humans and Neanderthals, very large differences were found. If we take a section of DNA, then out of 370 nucleotides, 27 differ. And if we compare the genetic texts of a modern person, his mitochondrial DNA, then only eight nucleotides differ. It is believed that the Neanderthal and modern man are completely separate branches, the evolution of each of them was independent of each other.

When studying the difference in the genetic texts of the mitochondrial DNA of Neanderthal and modern humans, the date of separation of these two branches was established. This happened about 500 thousand years ago, and about 300 thousand years ago their final separation took place. It is believed that Neanderthals settled in Europe and Asia and were supplanted by modern humans, who left Africa 200 thousand years later. And finally, about 28 - 35 thousand years ago, the Neanderthals died out. Why this happened, in general, is not yet clear. Maybe they could not stand the competition with a modern type of person, or maybe there were other reasons for this.

DNA in mitochondria is represented by cyclic molecules that do not form bonds with histones, in this respect they resemble bacterial chromosomes.
In humans, mitochondrial DNA contains 16.5 thousand bp, it is completely deciphered. It was found that the mitochondral DNA of various objects is very homogeneous, their difference lies only in the size of introns and non-transcribed regions. All mitochondrial DNA is represented by multiple copies, collected in groups, clusters. Thus, one rat liver mitochondria can contain from 1 to 50 cyclic DNA molecules. The total amount of mitochondrial DNA per cell is about one percent. Synthesis of mitochondrial DNA is not associated with DNA synthesis in the nucleus. Just like in bacteria, mitochondral DNA is assembled into a separate zone - the nucleoid, its size is about 0.4 microns in diameter. In long mitochondria, there can be from 1 to 10 nucleoids. When a long mitochondrion divides, a section containing a nucleoid is separated from it (similar to the binary fission of bacteria). The amount of DNA in individual mitochondrial nucleoids can vary by 10 times depending on the cell type. When mitochondria merge, their internal components can be exchanged.
rRNA and ribosomes of mitochondria differ sharply from those in the cytoplasm. If 80s ribosomes are found in the cytoplasm, then mitochondrial ribosomes of plant cells belong to 70s ribosomes (they consist of 30s and 50s subunits, contain 16s and 23s RNAs characteristic of prokaryotic cells), and smaller ribosomes (about 50s) are found in animal cell mitochondria. Protein synthesis takes place in the mitoplasm on ribosomes. It stops, in contrast to the synthesis on cytoplasmic ribosomes, under the action of the antibiotic chloramphenicol, which suppresses protein synthesis in bacteria.
Transfer RNAs are also synthesized on the mitochondrial genome; in total, 22 tRNAs are synthesized. The triplet code of the mitochondrial synthetic system is different from that used in the hyaloplasm. Despite the presence of seemingly all the components necessary for protein synthesis, small mitochondrial DNA molecules cannot encode all mitochondrial proteins, only a small part of them. So DNA is 15 kb in size. can encode proteins with a total molecular weight of about 6x105. At the same time, the total molecular weight of the proteins of a particle of a complete mitochondrial respiratory ensemble reaches a value of about 2x106.

Rice. Relative sizes of mitochondria in various organisms.

Of interest are observations of the fate of mitochondria in yeast cells. Under aerobic conditions, yeast cells have typical mitochondria with well-defined cristae. When cells are transferred to anaerobic conditions (for example, when they are subcultured or when they are transferred to a nitrogen atmosphere), typical mitochondria are not found in their cytoplasm, and small membrane vesicles are visible instead. It turned out that under anaerobic conditions, yeast cells do not contain a complete respiratory chain (there are no cytochromes b and a). During aeration of the culture, a rapid induction of the biosynthesis of respiratory enzymes, a sharp increase in oxygen consumption, and normal mitochondria appear in the cytoplasm.
Settlement of people on Earth

Ecology of consumption. Health: Haplogroup - a group of similar haplotypes that have a common ancestor, in which the same mutation took place in both haplotypes ...

When I was still a child, I asked my grandmother about the roots, she told a legend that her distant great-grandfather married a "local" girl. I became interested in this and undertook a little research. Veps, local to the Vologda region, are the Finno-Ugric people. To accurately test this family legend, I turned to genetics. And she confirmed the family legend.

Haplogroup (in human population genetics - a science that studies the genetic history of mankind) - a group of similar haplotypes that have a common ancestor, in which the same mutation took place in both haplotypes. The term "haplogroup" is widely used in genetic genealogy, where the Y-chromosomal (Y-DNA), mitochondrial (mtDNA) and MHC haplogroups are studied. Genetic markers of Y-DNA are transmitted with the Y-chromosome exclusively through the paternal line (that is, from father to sons), and mtDNA markers through the maternal line (from mother to all children).

Mitochondrial DNA (mtDNA) is passed from mother to child. Because only females can pass on mtDNA to their offspring, mtDNA testing provides information about the mother, her mother, and so on through the direct maternal line. Both men and women receive mtDNA from their mothers, so both men and women can participate in mtDNA testing. Although mutations do occur in mtDNA, their frequency is relatively low. Over the millennia, these mutations have accumulated, and for this reason the female line in one family is genetically different from another. After humanity settled on the planet, mutations continued to randomly appear in widely separated populations of the once single human race.

Migration of mitochondrial haplogroups.

Russian north.

I am very close to the history, nature and culture of the Russian North. This is also because my grandmother comes from there, who lived with us and devoted a lot of time to my upbringing. But I think that for Belarusians the proximity is even greater: after all, the Russian north was inhabited by the Krivichi, who also formed the core of the future Belarus. In addition, Pskov and Novgorod are ancient Slavic centers, democratic to a certain extent, with their own veche (just like Kyiv and Polotsk).

Suffice it to recall the history of the Pskov Veche Republic and the Novgorod Republic. For a long time these territories fluctuated between the Grand Duchy of Lithuania and the Principality of Moscow, but the latter seized the initiative in "collecting lands." Under other circumstances, the identity of this region could develop into an independent nationality. However, many proudly call themselves "Northern Russians." As well as some Belarusians, they distinguish Western Belarus (Lithuania, Litvinians) from Eastern Belarus (Rusyns). I ask you not to look for any political background in my words.

If in Belarus the Slavs mixed with the Baltic tribes, then in Russia - with the Finno-Ugric ones. This provided the unique ethnicity of different regions. Parfyonov, who comes from neighboring villages, said very accurately: “I always feel my origin. Northern Russian - for me it is very important. This is my idea of ​​Russia, our character, ethics and aesthetics. South of Voronezh for me are other Russians. It is curious that there are Parfenovs in my family. Aksinya Parfenova (1800-1904) is the grandmother of Kirill Kirillovich Korichev (husband of Alexandra Alekseevna Zemskova). However, this surname is common, so maybe relatives, or maybe not.

Cherepovets, great-grandmother on the left, grandmother on the bottom right, 1957?

My mitochondrial group is D5a3a.

When sequencing GVS1 - 16126s, 16136s, 16182s, 16183s, 16189s, 16223T, 16360T, 16362S. This means that my mitochondrial group is D5a3a. This is a very rare haplogroup, even geneticists were surprised - this is the first time such a group has been determined in Belarus. In general, D is an Asian group. Scientists write that it is found in the gene pools of only some ethnic groups of Northern Eurasia.

Single D5a3 lines were found in Tajiks, Altaians, Koreans, and Russians of Veliky Novgorod. All of them (with the exception of the Korean) are characterized by the 16126-16136-16360 GVS1 motif, which is also found in some populations of Northeastern Europe.

Annino village, 1917, my great-grandmother.

Whole genome analysis showed that the mtDNA of the Russian and Mansi are combined into a separate cluster D5a3a, and the mtDNA of the Korean is represented by a separate branch. The evolutionary age of the entire D5a3 haplogroup is about 20 thousand years (20560 ± 5935), while the degree of divergence of the D5a3a mtDNA lines corresponds to about 5 thousand years (5140 ± 1150). D5 is a distinctly East Asian group.

In Siberia, D4 variants absolutely predominate. D5 is most numerous and diverse in Japan, Korea, and southern China. Among the Siberian peoples, the diversity of D5 and the presence of its unique purely ethnic variants were noted among the eastern Mongol-speaking groups, including the Mongolized Evenks. D5a3 is noted in an archaic variant in Korea. A more accurate analysis shows the age of D5a3a up to 3000 years, but the parent D5a3 is very ancient, there is probably the Mesolithic.

Cherepovets, 1940

Based on the available data, it seems logical to suggest the origin of D5a3 somewhere in Far East(between Mongolia and Korea) and its migration to the west through South Siberia. It is likely that my direct female ancestors came to Europe about three thousand years ago, having given roots in Finland, Korea, among the local Finno-Ugric peoples: the Sami, Karelians and Vepsians. When mixed with the Krivichi, these haplogroups passed to the modern inhabitants of Vologda and the Novgorod region.

What is mitochondrial DNA?

Mitochondrial DNA (mtDNA) is DNA located in mitochondria, cell organelles within eukaryotic cells that convert chemical energy from food into a form that cells can use it - adenosine triphosphate (ATP). Mitochondrial DNA is only a small portion of the DNA in a eukaryotic cell; most DNA can be found in the cell nucleus, in plants and algae, and in plastids such as chloroplasts.

In humans, 16,569 base pairs of mitochondrial DNA code for a total of 37 genes. Human mitochondrial DNA was the first significant portion of the human genome to be sequenced. In most species, including humans, mtDNA is inherited only from the mother.

Because animal mtDNA evolves faster than nuclear genetic markers, it is the basis of phylogenetics and evolutionary biology. This has become an important point in anthropology and biogeography, as it allows you to study the relationship of populations.

Hypotheses of the origin of mitochondria

Nuclear and mitochondrial DNA are believed to have different evolutionary origins, with mtDNA derived from the circular genomes of bacteria that were engulfed by the early ancestors of modern eukaryotic cells. This theory is called the endosymbiotic theory. It is estimated that each mitochondria contains copies of 2-10 mtDNA. In the cells of extant organisms, the vast majority of the proteins present in mitochondria (numbering about 1500 different types in mammals) are encoded by nuclear DNA, but the genes for some, if not most, are thought to be originally bacterial; they have since been transferred to the eukaryotic nucleus. during evolution.

The reasons why mitochondria retain certain genes are discussed. The existence of genome-less organelles in some species of mitochondrial origin suggests that complete gene loss is possible, and the transfer of mitochondrial genes to the nucleus has a number of advantages. The difficulty in orienting remotely produced hydrophobic protein products in mitochondria is one of the hypotheses for why some genes are conserved in mtDNA. Co-localization for redox regulation is another theory, referring to the desirability of localized control over mitochondrial mechanisms. Recent analysis of a wide range of mitochondrial genomes suggests that both of these functions may dictate mitochondrial gene retention.

Genetic expertise of mtDNA

In most multicellular organisms, mtDNA is inherited from the mother (maternal line). Mechanisms for this include simple breeding (an egg contains an average of 200,000 mtDNA molecules, while healthy human sperm contains an average of 5 molecules), degradation of mtDNA sperm in the male reproductive tract, in a fertilized egg, and, in at least a few organisms, the inability to The mtDNA of the sperm penetrate the egg. Whatever the mechanism, this is unipolar inheritance—mtDNA inheritance—which occurs in most animals, plants, and fungi.

maternal inheritance

In sexual reproduction, mitochondria are usually inherited exclusively from the mother; mitochondria in mammalian sperm are usually destroyed by the egg after fertilization. In addition, most mitochondria are present at the base of the sperm tail, which is used to propel the sperm cells; sometimes the tail is lost during fertilization. In 1999, paternal sperm mitochondria (containing mtDNA) were reported to be marked with ubiquitin for subsequent destruction within the embryo. Some methods of in vitro fertilization, in particular the injection of sperm into the oocyte, can interfere with this.

The fact that mitochondrial DNA is maternally inherited allows genealogists to trace the maternal line far back in time. (Y-chromosomal DNA is paternally inherited, used in a similar way to determine patrilineal history.) This is usually done on human mitochondrial DNA by sequencing the hypervariable control region (HVR1 or HVR2) and sometimes the entire mitochondrial DNA molecule as a genealogical DNA test. For example, HVR1 is approximately 440 base pairs long. These 440 pairs are then compared to control regions of other individuals (either specific individuals or subjects in the database) to determine the maternal lineage. The most common comparison is with the revised Cambridge reference sequence. Vila et al. published studies on the matrilineal resemblance of domestic dogs and wolves. The concept of Mitochondrial Eve is based on the same type of analysis, trying to discover the origin of humanity, tracing the origin back in time.

mtDNA is highly conserved, and its relatively slow mutation rates (compared to other regions of DNA such as microsatellites) make it useful for studying evolutionary relationships—the phylogeny of organisms. Biologists can identify and then compare mtDNA sequences across species and use the comparisons to build an evolutionary tree for the studied species. However, due to the slow mutation rates it experiences, it is often difficult to distinguish closely related species to any degree, so other methods of analysis must be used.

Mitochondrial DNA mutations

Individuals subject to unidirectional inheritance and almost no recombination can be expected to undergo Muller's ratchet, an accumulation of detrimental mutations until functionality is lost. Animal populations of mitochondria escape this accumulation due to a developmental process known as the mtDNA bottleneck. The bottleneck uses stochastic processes in the cell to increase cell-to-cell variability in the mutant load as the organism develops such that a single egg with some mutant mtDNA creates an embryo in which different cells have different mutant loads. The cellular level can then be chosen to remove those cells with more mutant mtDNA, resulting in a stabilization or reduction in mutant load between generations. The underlying mechanism of the bottleneck is discussed with recent mathematical and experimental metastaging and provides evidence for a combination of random splitting of mtDNA into cell divisions and random turnover of mtDNA molecules within the cell.

paternal inheritance

Bifold unidirectional mtDNA inheritance is observed in bivalves. In these species, females have only one type of mtDNA (F), whereas males have type F mtDNA in their somatic cells, but M type mtDNA (which can be as high as 30% divergent) in their germline cells. In maternally inherited mitochondria, some insects have additionally been reported, such as fruit flies, bees, and periodic cicadas.

Male mitochondrial inheritance was recently discovered in Plymouth Rock chicks. Evidence supports rare cases of male mitochondrial inheritance in some mammals. In particular, documented cases exist in mice where male inherited mitochondria have subsequently been rejected. In addition, it has been found in sheep as well as cloned cattle. Once was found in the body of a man.

While many of these cases involve embryo cloning or subsequent rejection of paternal mitochondria, others document inheritance and persistence in vivo in the laboratory.

Mitochondrial donation

The IVF method, known as mitochondrial donation or mitochondrial replacement therapy (MRT), results in offspring containing mtDNA from female donors and nuclear DNA from mother and father. In the spindle transfer procedure, an egg nucleus is injected into the cytoplasm of an egg from a female donor that has had its nucleus removed but still contains the mtDNA of the female donor. The composite egg is then fertilized with the male's sperm. This procedure is used when a woman with genetically defective mitochondria wants to produce offspring with healthy mitochondria. The first known baby to be born from a mitochondrial donation was a boy born to a Jordanian couple in Mexico on April 6, 2016.

Mitochondrial DNA structure

In most multicellular organisms, the mtDNA - or mitogenome - is organized as a round, circularly closed, double-stranded DNA. But in many unicellular organisms (eg, tetrachymenes or the green algae Chlamydomonas reinhardtii) and rarely in multicellular organisms (eg, some species of cnidarians), mtDNA is found as linearly organized DNA. Most of these linear mtDNAs have telomerase-independent telomeres (that is, the ends of linear DNA) with different replication modes, which have made them interesting subjects of study, since many of these single-celled organisms with linear mtDNA are known pathogens.

For human mitochondrial DNA (and probably for metazoans), 100-10,000 individual copies of mtDNA are typically present in a somatic cell (eggs and sperm are exceptions). In mammals, each double-stranded circular mtDNA molecule consists of 15,000-17,000 base pairs. The two strands of mtDNA differ in their nucleotide content, the guanide-rich strand is called the heavy chain (or H-strand) and the cynosine-rich strand is called the light chain (or L-strand). The heavy chain codes for 28 genes and the light chain codes for 9 genes, for a total of 37 genes. Of the 37 genes, 13 are for proteins (polypeptides), 22 for the transmission of RNA (tRNA), and two for small and large subunits of ribosomal RNA (rRNA). The human mitogenome contains overlapping genes (ATP8 and ATP6, as well as ND4L and ND4: see Map of the Human Genome of Mitochondria), which is rare in animal genomes. The 37-gene pattern is also found among most metazoans, although, in some cases, one or more of these genes is missing and the mtDNA size range is greater. More greater change The content and size of mtDNA genes exists among fungi and plants, although there appears to be a core subset of genes that is present in all eukaryotes (with the exception of a few that do not have mitochondria at all). Some plant species have huge mtDNA (as many as 2,500,000 base pairs per mtDNA molecule), but surprisingly, even these huge mtDNA contain the same number and kinds of genes as related plants with much smaller mtDNA.

The mitochondrial genome of the cucumber (Cucumis Sativus) consists of three circular chromosomes (1556, 84, and 45 kb in length) that are completely or largely autonomous with respect to their replication.

Six major genome types have been found in mitochondrial genomes. These types of genomes have been classified by "Kolesnikov and Gerasimov (2012)" and differ in various ways such as circular versus linear genome, genome size, the presence of introns or similar plasmid structures, and whether the genetic material is a singular molecule, a collection of homogeneous or heterogeneous molecules.

Deciphering the animal genome

In animal cells, there is only one type of mitochondrial genome. This genome contains one circular molecule between 11-28 kbp of genetic material (type 1).

Deciphering the plant genome

There are three different types of genome found in plants and fungi. The first type is a circular genome that has introns (type 2) ranging in length from 19 to 1000 kbp. The second type of genome is a circular genome (about 20-1000 kbp), which also has a plasmid structure (1kb) (type 3). The final type of genome that can be found in plants and fungi is a linear genome composed of homogeneous DNA molecules (type 5).

Deciphering the protist genome

Protists contain a wide variety of mitochondrial genomes, which include five different types. The type 2, type 3, and type 5 mentioned in the plant and fungal genome also exist in some protozoa, as well as in two unique genome types. The first of these is a heterogeneous collection of circular DNA molecules (type 4) and the final genome type found in protists is a heterogeneous collection of linear molecules (type 6). Genome types 4 and 6 range from 1 to 200 kb.,

Endosymbiotic gene transfer, the process of genes encoded in the mitochondrial genome, is carried primarily by the genome of the cell, probably explaining why more complex organisms such as humans have smaller mitochondrial genomes than simpler organisms such as protozoa.

Mitochondrial DNA replication

Mitochondrial DNA is replicated by the DNA polymerase gamma complex, which consists of a 140 kD catalytic DNA polymerase encoded by the POLG gene and two 55 kD accessory subunits encoded by the POLG2 gene. The replication device is formed by DNA polymerase, TWINKLE, and mitochondrial SSB proteins. TWINKLE is a helicase that unwinds short lengths of dsDNA in a 5" to 3" direction.

During embryogenesis, mtDNA replication is tightly regulated from the fertilized oocyte through the pre-implantation embryo. The effective reduction in the number of cells in each cell mtDNA plays a role in the mitochondrial bottleneck exploiting cell-to-cell variability to improve the inheritance of deleterious mutations. At the blastocyte stage, the start of mtDNA replication is specific for trophtocoder cells. In contrast, cells in the inner cell mass restrict mtDNA replication until they receive signals to differentiate into specific cell types.

Transcription of mitochondrial DNA

In animal mitochondria, each strand of DNA is continuously transcribed and produces a polycistronic RNA molecule. Between most (but not all) protein-coding regions, tRNAs are present (see Human Mitochondrial Genome Map). During transcription, tRNA takes on a characteristic L-shape that is recognized and cleaved by specific enzymes. Upon processing of mitochondrial RNA, individual fragments of mRNA, rRNA, and tRNA are released from the primary transcript. Thus, stacked tRNAs act as secondary punctuations.

Mitochondrial diseases

The notion that mtDNA is particularly susceptible to reactive oxygen species generated by the respiratory chain due to its proximity remains controversial. mtDNA does not accumulate more oxidative base than nuclear DNA. It has been reported that at least some types of oxidative DNA damage are repaired more efficiently in the mitochondria than in the nucleus. mtDNA is packaged with proteins that appear to be as protective as nuclear chromatin proteins. Moreover, mitochondria have evolved a unique mechanism that maintains mtDNA integrity by degrading excessively damaged genomes, followed by replication of intact/repaired mtDNA. This mechanism is absent in the nucleus and is activated by the few copies of mtDNA present in mitochondria. The result of a mutation in mtDNA may be a change in the coding instructions for some proteins, which may affect the metabolism and/or fitness of the organism.

Mitochondrial DNA mutations can lead to a number of diseases, including exercise intolerance and Kearns-Saire syndrome (KSS), which causes a person to lose full function of heart, eye, and muscle movements. Some evidence suggests that they may contribute significantly to the aging process and are associated with age-related pathology. In particular, in the context of disease, the proportion of mutant mtDNA molecules in a cell is referred to as heteroplasm. The distributions of heteroplasm within and between cells dictate the onset and severity of disease and are influenced by complex stochastic processes within the cell and during development.

Mutations in mitochondrial tRNAs may be responsible for severe diseases such as the MELAS and MERRF syndromes.

Mutations in nuclear genes that code for proteins that mitochondria use can also contribute to mitochondrial disease. These diseases do not follow mitochondrial inheritance patterns, but instead follow Mendelian inheritance patterns.

Recently, mutations in mtDNA have been used to help diagnose prostate cancer in biopsy negative patients.

Mechanism of aging

Although the idea is controversial, some evidence suggests a link between aging and mitochondrial genome dysfunction. In essence, mutations in mtDNA upset the careful balance of reactive oxygen (ROS) production and enzymatic ROS production (by enzymes such as superoxide dismutase, catalase, glutathione peroxidase, and others). However, some mutations that increase ROS production (for example, by reducing antioxidant defenses) in worms increase rather than decrease their longevity. In addition, naked mole rats, mouse-sized rodents, live about eight times longer than mice, despite reduced, compared to mice, antioxidant defenses and increased oxidative damage to biomolecules.

At one point, there was considered to be a positive feedback loop at work ("Vicious Cycle"); as mitochondrial DNA accumulates genetic damage caused by free radicals, mitochondria lose function and release free radicals into the cytosol. Decreased mitochondrial function reduces overall metabolic efficiency. However, this concept was definitively disproved when mice genetically engineered to accumulate mtDNA mutations at an increased rate were shown to age prematurely, but their tissues do not produce more ROS, as predicted by the Vicious Cycle Hypothesis. Supporting the relationship between longevity and mitochondrial DNA, some studies have found correlations between biochemical properties of mitochondrial DNA and species longevity. Extensive research is being done to further explore this connection and anti-aging methods. Currently, gene therapy and nutraceutical supplements are popular areas of current research. Bjelakovic et al. analyzed results from 78 studies between 1977 and 2012, involving a total of 296,707 participants, concluded that antioxidant supplements do not reduce all-cause mortality or prolong life expectancy, while some them, such as beta-carotene, vitamin E, and higher doses of vitamin A, may actually increase mortality.

Deletion breakpoints are often found within or near regions showing non-canonical (non-B) conformations, namely hairpins, cruciforms, and clover-like features. In addition, there is evidence to support the involvement of helical curvilinear regions and long G-tetrads in detecting instability events. In addition, higher density points were consistently observed in regions with GC skew and in close proximity to the degenerate fragment of the YMMYMNNMMHM sequence.

How is mitochondrial DNA different from nuclear?

Unlike nuclear DNA, which is inherited from both parents and in which genes are rearranged through recombination, there is usually no change in mtDNA from parent to offspring. While mtDNA also recombines, it does so with copies of itself within the same mitochondrion. Because of this, the mutation rate of animal mtDNA is higher than that of nuclear DNA. mtDNA is a powerful tool for tracing ancestry through females (matrilineage) and has been used in this role to trace the ancestry of many species hundreds of generations ago.

The rapid mutation rate (in animals) makes mtDNA useful for assessing the genetic relationships of individuals or groups within a species, and for identifying and quantifying phylogeny (evolutionary relationships) among different species. To do this, biologists determine and then compare the mtDNA sequence from different individuals or species. Comparison data is used to construct a network of relationships between sequences that provide an estimate of relationships between individuals or species from which the mtDNA was taken. mtDNA can be used to assess relationships between closely related and distant species. Due to the high frequency of mtDNA mutations in animals, position 3 codons change relatively quickly, and thus provides information about genetic distances between closely related individuals or species. On the other hand, the rate of substitution of mt proteins is very slow, so amino acid changes accumulate slowly (with corresponding slow changes in codon 1 and 2 positions) and thus provide information about the genetic distances of distant relatives. Statistical models that account for substitution frequency among codon positions separately can therefore be used to simultaneously estimate a phylogeny that contains both closely related and distant species.

History of mtDNA discovery

Mitochondrial DNA was discovered in the 1960s by Margit M. K. Nas and Sylvan Nas using electron microscopy as DNase-sensitive strands within mitochondria, and by Ellen Hasbrunner, Hans Tuppi, and Gottfried Schatz from biochemical analyzes on highly purified mitochondrial fractions.

Mitochondrial DNA was first recognized in 1996 during the Tennessee v. Paul Ware. In 1998, in the Commonwealth of Pennsylvania v. Patricia Lynn Rorrer, mitochondrial DNA was admitted into evidence for the first time in the state of Pennsylvania. The case was featured in episode 55 of Season 5 of the True Series of Dramatic Forensic Court Cases (Season 5).

Mitochondrial DNA was first recognized in California during the successful prosecution of David Westerfield for the 2002 kidnapping and murder of 7-year-old Danielle van Dam in San Diego: it was used to identify both humans and dogs. This was the first trial in the US to resolve canine DNA.

mtDNA databases

Several specialized databases have been created to collect mitochondrial genome sequences and other information. Although most of them focus on sequence data, some of them include phylogenetic or functional information.

• MitoSatPlant: Mitochondrial Viridiplant Microsatellite Database.

• MitoBreak: Mitochondrial DNA Checkpoint Database.

• MitoFish and MitoAnnotator: a database of the mitochondrial genome of fish. See also Cawthorn et al.

• MitoZoa 2.0: database for comparative and evolutionary analysis of mitochondrial genomes (no longer available)

• InterMitoBase: an annotated database and platform for the analysis of protein-protein interactions for human mitochondria (last updated in 2010, but still not available)

• Mitome: database for comparative mitochondrial genomics in metazoans (no longer available)

• MitoRes: a resource for nuclear-encoded mitochondrial genes and their products in metazoa (no longer updated)

There are several specialized databases that report on polymorphisms and mutations in human mitochondrial DNA along with an assessment of their pathogenicity.

• MITOMAP: a compendium of polymorphisms and mutations in human mitochondrial DNA.

• MitImpact: Collection of predictive pathogenicity predictions for all nucleotide changes that cause non-synonymous substitutions in genes encoding human mitochondrial proteins.

Examples of mitochondrial inheritance are antibiotic resistance in yeast cells and male sterility (absence of male gametes) in a number of plants, such as corn.

In humans (presumably) - such malformations as fusion of the lower extremities and spina bifida.

centriolar inheritance

Examples of signs transmitted through centrioles have not yet been established.

In the cytoplasm of bacteria, small circular DNA molecules are autonomously located - plasmids. Three types of plasmids have been isolated.

Plasmids containing F-factor (fertility factor): F+ (male), F- (female). During conjugation, the factor can pass from one bacterium to another, i.e. gender changes.

Plasmids containing the R-factor (resistance factor) determine antibiotic resistance. They can also pass from one bacterium to another.

Colicinogen plasmids - encode proteins that have a detrimental effect on individuals of the same species that do not contain colicinogens (killer bacteria).

The genes of the nucleus and cytoplasm interact with each other. They are based on known forms of interaction of non-allelic genes such as epistasis (for example, nuclear genes suppress cytoplasmic genes).

There is also pseudocytoplasmic heredity due to the presence of symbionts in cells - bacteria or viruses. So, Drosophila has a race with increased sensitivity to CO 2. In the cells of this race there are viruses that determine this property.

Some ciliates-shoes ("killers") secrete substances that have a detrimental effect on other individuals of the same species. Bacteria are found in their cells.

In mice, there is a race with a hereditary predisposition to breast cancer. Transmission occurs through mother's milk containing viruses. If we exclude the feeding of offspring with this milk, then there will be no predisposition to cancer, and vice versa, if the offspring of a healthy race are fed with this milk, then they will develop a predisposition to cancer.

Variability

Variability - the property of living organisms to change both the very hereditary information received from parents and the process of its implementation in the course of ontogenesis.

There are three types of variability:

phenotypic,

ontogenetic,

genotypic.

Phenotypic, or modification variability - change in the phenotype in response to the action of environmental factors. This type of variability was identified by C. Darwin and named by him " certain". The traits acquired during ontogenesis are not inherited. The limits of variability of a trait are called reaction norm. The rate of reaction is inherited. It can be wide or narrow. (Give examples.)

For the evolutionary process, phenotypic variability is of great importance, because. natural selection of individuals in nature is based on the phenotype.

ontogenetic variability - a regular change in the genotype and phenotype during ontogenesis.

Changes in the phenotype of the human body in the process of growth, the appearance of secondary sexual characteristics are examples of ontogenetic variability.

A regular change in the genotype during ontogenesis has been recently discovered. However, few such examples are known. Thus, immunoglobulin proteins in mice consist of two fractions: V (variable) and C (constant). In mouse embryos, the genes encoding them are located at a fairly large distance from each other:

In adult mice, these genes are connected and work as one:

Genotypic variability due to a change in the genotype. Ch. Darwin called this type of variability “ uncertain". This is hereditary variability (passed on by inheritance).

Genotypic variability is divided into two types: combinative and mutational .

Combination variability due to the recombination of existing genetic material.

There are three sources of combinative variability in nature:

1) independent divergence of chromosomes in meiosis (the number of combinations is

2 n , where n is the number of chromosomes in the haploid set);

2) crossing over (exchange of homologous regions between homologous

chromosomes);

3) random combination of chromosomes during fertilization.

All this leads to a huge variety of genotypes and phenotypes, which, in turn, ensures the high adaptability of species.

At the core mutational variability lies in the restructuring of the genetic apparatus.