The first division of meiosis is brief. Meiosis. Phases of meiosis. Prophase II is very short. It is characterized by the spiralization of chromosomes, the disappearance of the nuclear membrane and nucleolus, and the formation of a fission spindle.

The essence of meiosis- education cells with a haploid set of chromosomes.

Meiosis consists of two successive divisions.

Between them not happening DNA replication – that’s why the set is haploid.

Thanks to this process, the following occurs:

• gametogenesis;
• c pore formation in plants;
• and variability of hereditary information

Now let's take a closer look at this process.

Meiosis represents 2 divisions, following each other.

As a result, they are usually formed four cells(except for example, where after the first division, the second cell does not divide further, but is reduced immediately).

There is another important point here: as a result of meiosis, as a rule, three out of four cells are reduced, leaving one, that is, natural selection. This is also one of the tasks of meiosis.

Interphase first division:

the cell transitions from the state 2n2c to 2n4c, since DNA replication has occurred.

Prophase:

In the first division, an important process occurs - crossing over.

In prophase I of meiosis, each of the already twisted bichromatid chromosomes, univalents close relationship with homologous to her. This is called (well confused with conjugation of ciliates), or synapsis. A pair of homologous chromosomes that come together is called

The chromatid then crosses over with a homologous (non-sister) chromatid on the neighboring chromosome (with which it is formed bivalent). The place where chromatids intersect is called. Chiasmus discovered in 1909 by the Belgian scientist Frans Alphonse Janssens.

And then a piece of chromatid breaks off in place chiasmata and jumps to another (homologous, i.e., non-sister) chromatid.

Happened gene recombination .

Result: some genes migrated from one homologous chromosome to another.

Before crossing over one homologous chromosome possessed genes from the maternal organism, and the second from the paternal one. And then both homologous chromosomes possess the genes of both the maternal and paternal organism.

Meaning crossing over This is: as a result of this process, new combinations of genes are formed, therefore there is more hereditary variability, and therefore there is a greater likelihood of the emergence of new traits that may be useful.

Synapsis (conjugation) always occurs during meiosis, but crossing over may not happen.

Because of all these processes: conjugation, crossing over prophase I is longer than prophase II.

Metaphase

The main difference between the first division of meiosis and

in mitosis, bichromatid chromosomes line up along the equator, and in the first division of meiosis bivalents homologous chromosomes, to each of which are attached spindle filaments.

Anaphase

due to the fact that they lined up along the equator bivalents, divergence of homologous bichromatid chromosomes occurs. Unlike mitosis, in which the chromatids of one chromosome separate.

Telophase

The resulting cells change from the 2n4c state to n2c, how again they differ from cells formed as a result of mitosis: firstly, they haploid. If in mitosis, at the end of division, absolutely identical cells are formed, then in the first division of meiosis, each cell contains only one homologous chromosome.

Errors in chromosome segregation during the first division can lead to trisomy. That is, the presence of one more chromosome in one pair of homologous chromosomes. For example, in humans, trisomy 21 is the cause of Down Syndrome.

Interphase between the first and second division

- either very short or not at all. Therefore, before the second division there is no DNA replication. This is very important, since the second division is generally necessary in order for cells to turn out haploid with single chromatid chromosomes.

Second division

- occurs almost the same as mitotic division. They only enter into division haploid cells with two-chromatid chromosomes (n2c), each of which is aligned along the equator, the spindle threads are attached to centromeres each chromatid of each chromosome in metaphaseII. IN anaphaseII chromatids separate. And in telophaseII are formed haploid cells with single chromatid chromosomes ( nc). This is necessary so that when merging with another similar cell (nc), a “normal” 2n2c is formed.

It is known about living organisms that they breathe, feed, reproduce and die; this is their biological function. But why does all this happen? Due to the bricks - cells that also breathe, feed, die and reproduce. But how does this happen?

About the structure of cells

The house is made of bricks, blocks or logs. Likewise, an organism can be divided into elementary units - cells. The entire diversity of living beings consists of them; the difference lies only in their quantity and types. They consist of muscles, bone tissue, skin, all internal organs - they differ so much in their purpose. But regardless of what functions a particular cell performs, they are all structured approximately the same. First of all, any “brick” has a shell and cytoplasm with organelles located in it. Some cells do not have a nucleus, they are called prokaryotic, but all more or less developed organisms consist of eukaryotes, which have a nucleus in which genetic information is stored.

Organelles located in the cytoplasm are diverse and interesting, they perform important functions. Cells of animal origin include the endoplasmic reticulum, ribosomes, mitochondria, Golgi complex, centrioles, lysosomes and motor elements. With their help, all the processes that ensure the functioning of the body take place.

Cell activity

As already mentioned, all living things eat, breathe, reproduce and die. This statement is true both for whole organisms, that is, people, animals, plants, etc., and for cells. It's amazing, but each "brick" has its own life. Due to its organelles, it receives and processes nutrients, oxygen, and removes everything unnecessary outside. The cytoplasm itself and the endoplasmic reticulum perform a transport function, mitochondria are also responsible for respiration, as well as providing energy. The Golgi complex is responsible for the accumulation and removal of cell waste products. Other organelles also participate in complex processes. And at a certain stage, it begins to divide, that is, the process of reproduction occurs. It is worth considering in more detail.

Cell division process

Reproduction is one of the stages of development of a living organism. The same applies to cells. At a certain stage in their life cycle, they enter a state where they are ready to reproduce. they simply divide in two, lengthening, and then forming a partition. This process is simple and almost completely studied using the example of rod-shaped bacteria.

Things are a little more complicated. They reproduce in three different ways, called amitosis, mitosis and meiosis. Each of these pathways has its own characteristics, it is inherent in a certain type of cell. Amitosis

considered the simplest, it is also called direct binary fission. When it occurs, the DNA molecule doubles. However, a fission spindle is not formed, so this method is the most energy-efficient. Amitosis occurs in unicellular organisms, while tissues of multicellular organisms reproduce using other mechanisms. However, it is sometimes observed where mitotic activity is reduced, for example, in mature tissues.

Direct fission is sometimes distinguished as a type of mitosis, but some scientists consider it a separate mechanism. This process occurs quite rarely even in old cells. Next, meiosis and its phases, the process of mitosis, as well as the similarities and differences of these methods will be considered. Compared to simple division, they are more complex and perfect. This is especially true for reduction division, so the characteristics of the phases of meiosis will be the most detailed.

An important role in cell division is played by centrioles - special organelles, usually located next to the Golgi complex. Each such structure consists of 27 microtubules, grouped in groups of three. The entire structure is cylindrical in shape. Centrioles are directly involved in the formation of the cell division spindle during the process of indirect division, which will be discussed later.

Mitosis

The lifespan of cells varies. Some live for a couple of days, and some can be classified as long-livers, since their complete change occurs very rarely. And almost all of these cells reproduce through mitosis. For most of them, an average of 10-24 hours passes between division periods. Mitosis itself takes a short period of time - in animals approximately 0.5-1

hour, and for plants about 2-3. This mechanism ensures the growth of the cell population and the reproduction of units identical in their genetic content. This is how the continuity of generations is maintained at the elementary level. In this case, the number of chromosomes remains unchanged. This mechanism is the most common type of reproduction of eukaryotic cells.

The significance of this type of division is great - this process helps tissues grow and regenerate, due to which the development of the entire organism occurs. In addition, it is mitosis that underlies asexual reproduction. And one more function is the movement of cells and the replacement of already obsolete ones. Therefore, it is incorrect to assume that because the stages of meiosis are more complex, its role is much higher. Both of these processes perform different functions and are important and irreplaceable in their own way.

Mitosis consists of several phases that differ in their morphological features. The state in which the cell is ready for indirect division is called interphase, and the process itself is divided into 5 more stages, which need to be considered in more detail.

Phases of mitosis

While in interphase, the cell prepares to divide: DNA and proteins are synthesized. This stage is divided into several more, during which the growth of the entire structure and doubling of chromosomes occurs. The cell remains in this state for up to 90% of its entire life cycle.

The remaining 10% is occupied by division itself, which is divided into 5 stages. During mitosis of plant cells, preprophase is also released, which is absent in all other cases. New structures are formed, the nucleus moves to the center. A preprophase ribbon is formed, marking the expected site of future division.

In all other cells, the process of mitosis proceeds as follows:

Table 1

After the division of genetic information is completed, cytokinesis or cytotomy occurs. This term refers to the formation of daughter cell bodies from the mother’s body. In this case, the organelles, as a rule, are divided in half, although exceptions are possible; a septum is formed. Cytokinesis is not separated into a separate phase; as a rule, it is considered within the framework of telophase.

So, the most interesting processes involve chromosomes, which carry genetic information. What are they and why are they so important?

About chromosomes

Even without the slightest idea about genetics, people knew that many qualities of the offspring depend on the parents. With the development of biology, it became obvious that information about a particular organism is stored in every cell, and part of it is transmitted to future generations.

At the end of the 19th century, chromosomes were discovered - structures consisting of a long

DNA molecules. This became possible with the improvement of microscopes, and even now they can only be seen during the division period. Most often, the discovery is attributed to the German scientist W. Fleming, who not only streamlined everything that had been studied before him, but also made his own contribution: he was one of the first to study cellular structure, meiosis and its phases, and also introduced the term “mitosis.” The very concept of “chromosome” was proposed a little later by another scientist - the German histologist G. Waldeyer.

The structure of chromosomes when they are clearly visible is quite simple - they are two chromatids connected in the middle by a centromere. It is a specific nucleotide sequence and plays an important role in the process of cell reproduction. Ultimately, the chromosome in appearance in prophase and metaphase, when it can be best seen, resembles the letter X.

In 1900, principles describing the transmission of hereditary characteristics were discovered. Then it became finally clear that chromosomes are exactly what genetic information is transmitted through. Subsequently, scientists conducted a number of experiments proving this. And then the subject of study was the influence that cell division has on them.

Meiosis

Unlike mitosis, this mechanism ultimately leads to the formation of two cells with a set of chromosomes that is 2 times less than the original one. Thus, the process of meiosis serves as a transition from the diploid phase to the haploid phase, and primarily

We are talking about the division of the nucleus, and secondly, the division of the entire cell. The restoration of the full set of chromosomes occurs as a result of further fusion of gametes. Due to the reduction in the number of chromosomes, this method is also defined as reduction cell division.

Meiosis and its phases were studied by such famous scientists as V. Fleming, E. Strasburger, V. I. Belyaev and others. The study of this process in cells of both plants and animals is still ongoing - it is so complex. Initially, this process was considered a variant of mitosis, but almost immediately after its discovery it was identified as a separate mechanism. The characteristics of meiosis and its theoretical significance were first sufficiently described by August Weissmann back in 1887. Since then, the study of the process of reduction division has greatly advanced, but the conclusions drawn have not yet been refuted.

Meiosis should not be confused with gametogenesis, although both processes are closely related. Both mechanisms are involved in the formation of germ cells, but there are a number of serious differences between them. Meiosis occurs in two stages of division, each of which consists of 4 main phases, with a short break between them. The duration of the entire process depends on the amount of DNA in the nucleus and the structure of the chromosomal organization. In general, it is much longer compared to mitosis.

By the way, one of the main reasons for significant species diversity is meiosis. As a result of reduction division, the set of chromosomes is split in two, so that new combinations of genes appear, primarily potentially increasing the adaptability and adaptability of organisms, which ultimately receive certain sets of characteristics and qualities.

Phases of meiosis

As already mentioned, reduction cell division is conventionally divided into two stages. Each of these stages is divided into 4 more. And the first phase of meiosis - prophase I, in turn, is divided into 5 more separate stages. As the study of this process continues, others may be identified in the future. Now the following phases of meiosis are distinguished:

table 2

So, it is obvious that the division phases of meiosis are much more complex than the process of mitosis. But, as already mentioned, this does not detract from the biological role of indirect division, since they perform different functions.

By the way, meiosis and its phases are also observed in some protozoa. However, as a rule, it includes only one division. It is assumed that this one-stage form later developed into the modern two-stage form.

Differences and similarities between mitosis and meiosis

At first glance, it seems that the differences between these two processes are obvious, because these are completely different mechanisms. However, upon deeper analysis, it turns out that the differences between mitosis and meiosis are not so global; in the end, they lead to the formation of new cells.

First of all, it’s worth talking about what these mechanisms have in common. In fact, there are only two coincidences: in the same sequence of phases, and also in the fact that

DNA replication occurs before both types of division. Although, as for meiosis, this process is not completely completed before the start of prophase I, ending at one of the first substages. And although the sequence of phases is similar, in essence, the events occurring in them do not completely coincide. So the similarities between mitosis and meiosis are not that many.

There are much more differences. First of all, mitosis occurs in while meiosis is closely related to the formation of germ cells and sporogenesis. In the phases themselves, the processes do not completely coincide. For example, crossing over in mitosis occurs during interphase, and not always. In the second case, this process involves anaphase of meiosis. Recombination of genes in indirect division usually does not occur, which means that it does not play any role in the evolutionary development of the organism and the maintenance of intraspecific diversity. The number of cells resulting from mitosis is two, and they are genetically identical to the mother and have a diploid set of chromosomes. During reduction division everything is different. The result of meiosis is 4 different from the maternal one. In addition, both mechanisms differ significantly in duration, and this is due not only to the difference in the number of division stages, but also to the duration of each stage. For example, the first prophase of meiosis lasts much longer, because at this time chromosome conjugation and crossing over occur. That is why it is further divided into several stages.

In general, the similarities between mitosis and meiosis are quite minor compared to their differences from each other. It is almost impossible to confuse these processes. Therefore, it is now somewhat surprising that reduction division was previously considered a type of mitosis.

Consequences of meiosis

As already mentioned, after the end of the reduction division process, instead of the mother cell with a diploid set of chromosomes, four haploid ones are formed. And if we talk about the differences between mitosis and meiosis, this is the most significant. Restoration of the required amount, when it comes to germ cells, occurs after fertilization. Thus, with each new generation the number of chromosomes does not double.

In addition, during meiosis occurs During the process of reproduction, this leads to the maintenance of intraspecific diversity. So the fact that even siblings are sometimes very different from each other is precisely the result of meiosis.

By the way, the sterility of some hybrids in the animal world is also a problem of reduction division. The fact is that the chromosomes of parents belonging to different species cannot enter into conjugation, which means that the process of formation of full-fledged viable germ cells is impossible. Thus, it is meiosis that underlies the evolutionary development of animals, plants and other organisms.

Meiosis occurs in the cells of organisms that reproduce sexually.

The biological meaning of the phenomenon is determined by a new set of characteristics in the descendants.

In this work, we will consider the essence of this process and, for clarity, we will present it in the figure, we will look at the sequence and duration of division of germ cells, and we will also find out the similarities and differences between mitosis and meiosis.

What is meiosis

A process accompanied by the formation of four cells with a single chromosome set from one original one.

The genetic information of each newly formed cell corresponds to half the set of somatic cells.

Phases of meiosis

Meiotic division involves two stages, consisting of four phases each.

First division

Includes prophase I, metaphase I, anaphase I and telophase I.

Prophase I

At this stage, two cells with half the set of genetic information are formed. The prophase of the first division includes several stages. It is preceded by pre-meiotic interphase, during which DNA replication occurs.

Condensation then occurs, the formation of long thin filaments with a protein axis during leptotene. This thread is attached to the nuclear membrane with the help of terminal extensions - attachment disks. The halves of the duplicated chromosomes (chromatids) are not yet distinguishable. When examined, they look like monolithic structures.

Next comes the zygotene stage. Homologs fuse to form bivalents, the number of which corresponds to a single number of chromosomes. The process of conjugation (connection) is carried out between pairs that are similar in genetic and morphological aspects. Moreover, the interaction begins from the ends, spreading along the chromosome bodies. A complex of homologues linked by a protein component – ​​a bivalent or tetrad.

Spiralization occurs during the thick filament stage, pachytene. Here the DNA duplication has already been completed completely, and crossing over begins. This is an exchange of homologous regions. As a result, linked genes with new genetic information are formed. Transcription occurs in parallel. Dense sections of DNA - chromomeres - are activated, which leads to a change in the structure of chromosomes like “lamp brushes”.

Homologous chromosomes condense, shorten, and diverge (except for the connection points - chiasmata). This is a stage in the biology of diplotene or dictyoten. Chromosomes at this stage are rich in RNA, which is synthesized in the same areas. In terms of properties, the latter is close to informational.

Finally, the bivalents disperse to the periphery of the nucleus. The latter shorten, lose their nucleoli, and become compact, not associated with the nuclear envelope. This process is called diakinesis (the transition to cell division).

Metaphase I

Next, the bivalents move to the central axis of the cell. Division spindles extend from each centromere, each centromere is equidistant from both poles. Small amplitude movements of the threads hold them in this position.

Anaphase I

Chromosomes, built from two chromatids, separate. Recombination occurs with a decrease in genetic diversity (due to the absence of homologs in the set of genes located in loci (regions).

Telophase I

The essence of the phase is the divergence of chromatids with their centromeres to opposite parts of the cell. In an animal cell, cytoplasmic division occurs, in a plant cell, the formation of a cell wall occurs.

Second division

After the interphase of the first division, the cell is ready for the second stage.

Prophase II

The longer the telophase, the shorter the duration of the prophase. Chromatids line up along the cell, forming a right angle with their axes relative to the threads of the first meiotic division. At this stage, they shorten and thicken, and the nucleoli undergo disintegration.

Metaphase II

The centromeres are again located in the equatorial plane.

Anaphase II

Chromatids separate from each other, moving towards the poles. Now they are called chromosomes.

Telophase II

Despiralization, stretching of formed chromosomes, disappearance of the spindle, doubling of centrioles. The haploid nucleus is surrounded by a nuclear membrane. Four new cells are formed.

Comparison table between mitosis and meiosis

The features and differences are briefly and clearly presented in the table.

The data presented is a diagram of the differences, and the similarities boil down to the same phases, DNA reduplication and helicalization before the start of the cell cycle.

Biological significance of meiosis

What is the role of meiosis:

1. Gives new combinations of genes due to crossing over.
2. Supports combinative variability. Meiosis is a source of new traits in a population.
3. Maintains a constant number of chromosomes.

Conclusion

Meiosis is a complex biological process during which four cells are formed, with new characteristics obtained as a result of crossing over.

Nikolay Mushkambarov, Dr. biol. sciences

Humanity is aging, but everyone wants to live not just long, but also without those diseases that come with age. Over the past half century, many “revolutionary” theories of aging have emerged, almost all of which offer a sure and reliable way to slow down or even stop time. Every year there are new sensations, new discoveries and new statements, encouraging and promising. Peptide bioregulators, elixir of longevity, life-giving ions, or antioxidant SkQ. Run to the pharmacy, pay and live, according to the included instructions, until you are 100-120 years old! To what extent can you trust sensational discoveries and what is the “truth about aging”?

Professor N. N. Mushkambarov. Photo by Andrey Afanasyev.

August Weismann (1834-1914) - German zoologist and evolutionist. Created a theory according to which hereditary characteristics are preserved and transmitted through ageless germplasm.

Leonard Hayflick is an American microbiologist. In the 1960s, he discovered that in laboratory conditions, human and animal cells can divide only a limited number of times.

Alexey Matveevich Olovnikov is a Russian biochemist. To explain Hayflick's experiments in 1971, he put forward a hypothesis about the shortening of the terminal sections of chromosomes (telomeres) with each cell division.

Science and life // Illustrations

Elizabeth Blackburn and Carol Greider are American biologists. In 1985, the enzyme telomerase was discovered. The mechanism of action of telomerase is the repeated encoding of new nucleotide sequences at the terminal sections of telomeres and the restoration of their original

Benjamin Gompertz (1779-1865) - British mathematician. He proposed a function that describes human mortality statistics depending on age. This function was used to assess risks in life insurance.

The book by M. M. Vilenchik “Biological basis of aging and longevity”, published in 1976, was one of the first popular science books on the topic of aging and enjoyed enormous success.

Scheme of meiosis (using the example of a pair of homologous chromosomes). In prophase of the first division of meiosis, chromosomes are doubled; then homologous chromosomes conjugate with each other and, while maintaining their activity, enter into crossing over.

Doctor of Biological Sciences, Professor of the Department of Histology at Moscow State Medical University named after N.V. I. M. Sechenov Nikolay Mushkambarov.

Nikolai Nikolaevich, you sharply criticize many well-known provisions of modern gerontology. Please outline the objects of your criticism.

There are more than enough objects! For example, it is now fashionable to refer to Weisman almost as the ultimate truth. This is a famous biologist who, back in the 19th century, postulated that aging did not arise immediately in evolution, but only at some stage as an adaptive phenomenon. From this they concluded that there must be non-aging species: first of all, the most primitive organisms. At the same time, they somehow forget that if they do not age, then they must have 100% DNA repair. This is among the most primitive! Somehow one doesn’t fit with the other.

There is a myth associated with the name of another famous biologist - Leonard Hayflick. Since the sixties of the last century, the scientific world has been confident that human somatic cells have a limit of 50 divisions, and such a limit in biology is called the “Hayflick limit”. About twenty years ago, stem cells were isolated that were supposedly capable of an unlimited number of divisions. And this myth (50 for everyone and infinity for stem cells) persists in the minds to this day. In fact, stem cells, as it turns out, age (that is, infinity is abolished), and it is not at all clear where to count these very 50 divisions. It is so unclear that, most likely, there is no single division limit that is universal for all dividing human cells.

- Well, what about the telomere theory of aging? Does she also make you distrustful?

This is the most popular myth. According to this theory, the entire mechanism of aging comes down to the fact that dividing cells lack the enzyme telomerase, which lengthens the ends of chromosomes (these ends are called telomeres), and therefore, with each division, telomeres are shortened by 50-100 DNA nucleotide pairs. The enzyme telomerase does exist, and its discovery was awarded the 2009 Nobel Prize. And the phenomenon of chromosome shortening in dividing cells lacking telomerase is also beyond doubt (although it is due to a slightly different reason than that pointed out by the author of the telomere theory, Alexey Olovnikov). But to reduce aging to this phenomenon is the same as replacing the most complex symphony score with notes of beating on a drum. It is no coincidence that in 2003 A. Olovnikov publicly abandoned his theory, replacing it with the so-called redumeric theory (also, by the way, not indisputable). But even today, even in medical universities, biology courses present the telomere theory as the latest achievement of scientific thought. This is, of course, absurd.

Another example comes from mortality statistics. The main formula for this statistics is the Gompertz equation, proposed in 1825, or, with a correction term, the Gompertz-Makem equation (1860). These equations have two and three coefficients, respectively, and the values ​​of the coefficients vary greatly among different populations of people. And it turns out that changes in the coefficients of each equation correlate with each other. On the basis of which global, worldwide patterns are formulated: the so-called Strehler-Mildvan correlation and the compensatory effect of mortality that replaced it in this post - the hypothesis of the Gavrilov spouses.

I compiled a small model for a conditional population of people and with its help I became convinced that all these patterns are most likely an artifact. The fact is that a small error in determining one coefficient creates a sharp deviation from the true value of another coefficient. And this is perceived (in semi-logarithmic coordinates) as a biologically significant correlation and serves as a promise for thoughtful conclusions.

- Are you sure that you are right when talking about the artifact?

Of course not! In general, it is harmful for scientists to be absolutely sure of something, although there are plenty of such examples. But I did my best to verify the opposite: that the correlations are not an artifact. And I was not able to verify this opposite. So for now, based on a personal, very modest in scale, analysis, I have more reason to believe that the named correlations are still artificial. They reflect the errors of the method, and not biological patterns.

How do you evaluate statements that there are a huge number of non-aging organisms in nature and their list is growing from year to year?

Alas, popular theories that there are both non-aging cells and non-aging organisms lack sufficient evidence. Indeed, every year the circle of “ageless” animals inexorably expands. At first these were practically only unicellular organisms, then lower multicellular organisms (hydra, mollusks, sea urchins, etc.) were added to them. And now hot heads have appeared who “discover” certain ageless species even among fish, reptiles and birds. So it will go - soon they will get to mammals and establish, for example, that elephants also do not age, but die simply due to excess body weight!

- Are you convinced that there are no ageless animals?

I am not convinced that there are no such animals (although I am inclined to do so), but that there is not a single species of animal for which the absence of aging has been proven absolutely reliably. With regard to human cells (as well as cells and other representatives of the animal world), the degree of confidence is perhaps even higher: stem cells, germ cells, and even tumor cells, in principle, age. Stem cells were considered indisputably ageless, but now experimental work is appearing that proves the opposite.

- What is this confidence based on? Have you carried out the relevant experiments yourself?

Generally speaking, a very long time ago, in 1977-1980, I tried to approach the problem of aging in experiments on mice. But the not very reliable results (although they seemed to confirm the initial assumption) convinced that it was better to do analysis rather than experimentation. And here is one of the results of this analysis - the concept of “Anerem”, or the ameiotic theory of aging. It includes six theses (postulates, if you like), of which one (the very first) is purely my work, and the rest are formulated on the basis of ideas already existing in the literature. And, of course, it is important that all these theses form a fairly clear picture as a whole.

So, it is the ameiotic concept, if adhered to, that excludes the possibility of the existence of both non-aging cells in multicellular organisms and non-aging organisms (starting with unicellular ones). At the same time, of course, I am aware that all theses of the concept are still hypotheses. But they seem much more reasonable than other views.

So, your concept is like a tester, with the help of which you can evaluate, relatively speaking, the truth of certain assumptions? In this case, tell us more about it.

I will try to make this as accessible as possible. The very name of the concept (“Anerem”) is an abbreviation for the words autocatalysis, instability, repair, meiosis. Thesis one. Do you remember that Engels’s definition of life was previously very well known: “Life is the way of existence of protein bodies”? I revised this definition and gave my own, which constituted the first thesis: “Life is a method of autocatalytic multiplication of DNA (less commonly RNA) in nature.” This means that the driving force behind both the emergence of life and its subsequent evolution is the indomitable desire of nucleic acids for endless self-reproduction. Essentially, any organism is an evolutionarily improved biomachine, designed to effectively preserve and multiply the genome it contains, followed by the effective distribution of its copies in the environment.

- It’s unusual to feel like a biomachine...

Nothing, the sensation will pass, but the function, excuse me, will remain. Thesis two: “Genome instability is a central element of aging.” This is exactly how most sensible scientists in the West, and here too, understand aging. The fact is that, for all their remarkable abilities, nucleic acids are susceptible to the damaging effects of many factors - free radicals, reactive oxygen species, etc. And although many protective systems have been created in evolution (such as the antioxidant system), numerous damage constantly occurs in the DNA strands. To detect and correct them, there is another protective system - DNA reparation (restoration). The next thesis, the third, is a filter that filters out everything “non-aging”: “Genome repair in mitotic and post-mitotic cells is not complete.” That is, any repair system in these cells does not provide 100% correction of all DNA defects that occur. And this means the universal nature of aging.

- But if everything and everyone ages, then how is life maintained on Earth?

Well, I became interested in this issue in 1977. And I found, as it seemed to me, my own answer, although lying on the surface. And 25 years later, in 2002, looking through my old books, I realized that this hypothesis was not mine at all, but I had read about it a year before in the book of M. M. Vilenchik, happily forgot and then remembered, but perceived it as your own. These are the quirks of memory. But in the end, it is the essence of the matter that is important, not the ambitions of the discoverer.

The essence is formulated by the fourth thesis: “Effective repair can be achieved only in meiosis (or in its simplified version - endomixis) - during the conjugation (fusion) of chromosomes.” Everyone seems to have learned what meiosis is in school, but, unfortunately, sometimes even our medical students do not know this. Let me remind you: meiosis is the last double division in the formation of germ cells - sperm and eggs. By the way, I’ll tell you a secret: women do not form eggs. In them, the second meiotic division (at the stage of oocyte II - the development of the female reproductive cell) cannot occur independently - without the help of a sperm. Because the cell has “lost” its centrioles (bodies in the cell involved in division) somewhere: they were just there (during the previous division), but now they’re gone somewhere. And fertilization of oocyte II is absolutely required for the sperm to bring in its centrioles and save the situation. I see this as typical “female things”. So the second meiotic division eventually occurs, but the resulting cell is no longer an egg, but a zygote.

We got carried away with “female things” and did not clarify how complete DNA repair is achieved in meiosis.

The first division of meiosis is preceded by a very long prophase: in male gametogenesis it lasts a whole month, and in female gametogenesis it lasts up to several decades! At this time, homologous chromosomes come closer to each other and remain in this state almost the entire time of prophase.

At the same time, enzymes are sharply activated, cutting and stitching DNA strands. It was believed that this was necessary only for crossing over - the exchange of chromosomes in their sections, which increases the genetic variability of the species. Indeed, “father’s” and “mother’s” genes, which are still distributed in each pair of homologous (structurally identical) chromosomes on different chromosomes, turn out to be mixed after crossing over.

But M. M. Vilenchik, and after him I, drew attention to the fact that crossing over enzymes are very similar to DNA repair enzymes, in which, by cutting out damaged areas, it is also necessary to break and stitch DNA strands. That is, DNA super-repair probably occurs simultaneously with crossing over. One can imagine other mechanisms of major “repair” of genes during meiosis. One way or another, in this case, a radical (more precisely, complete) “rejuvenation” of cells occurs, which is why mature germ cells begin counting time as if from scratch. If something doesn’t work out, then self-monitoring sensors for the state of its own DNA are triggered in the cell and the process of apoptosis starts - self-
killing the cell.

- So, in nature, rejuvenation occurs only in maturing germ cells?

Absolutely right. But this is quite enough to ensure the immortality of the species - against the background, alas, of the inevitable mortality of all individuals. After all, sex cells are the only ones! - the only material substrate of parent organisms from which new life is born - the life of the offspring.

And the fact that this mechanism concerns only germ cells is discussed in the two remaining theses of the concept, which dot all the i’s. Thesis five: “Meiosis improves the state of the genome only in subsequent generations (several generations at once in simple organisms and only one in all others).” Thesis six: “From here follow the inevitability of aging of individuals (individuals) and the relative immortality of the species as a whole.”

- What, meiosis occurs in all animal species?

It should be present in all animal species - according to the Anerem concept, if it turns out to be correct. Indeed, the concept is based on the universality of not only aging, but also meiosis. I thoroughly researched this issue using literature data. Of course, in sufficiently developed animals - fish and “higher” ones - there is only a sexual method of reproduction, which also implies the presence of meiosis. In addition, there are huge sectors of both flora and fauna in which mixed types of reproduction are common. This means that they alternate more or less prolonged acts of asexual reproduction (for example, mitotic divisions, sporulation, budding, fragmentation, etc.) and single acts of sexual or quasi-sexual reproduction. An essential feature of the quasi-sexual process (the so-called endomixis) is that here, too, there is a joining of structurally identical chromosomes from the paternal and maternal sets (conjugation of homologous chromosomes), although it does not end with their divergence into different cells.

Thus, with mixed reproduction, several generations of organisms live, as if gradually aging (similar to how mitotically dividing cells age in more complex animals), and then the sexual process returns individual organisms to “zero” age and provides
provides a comfortable life for several more generations. Finally, a number of simple animals are believed to reproduce only asexually. But in relation to them, I still have some doubt: did these organisms, in a long series of asexual reproduction, not see something similar to meiosis or endomixis (self-fertilization)?

It turns out that the concept you are developing puts an end to all dreams of extending human life. After all, ordinary (non-reproductive) cells are doomed to grow old and old?

No, I’m not putting up a cross. Firstly, because what is much more important for us is not the fact of aging itself, but the speed of this process. And you can influence the rate of aging by many means. Some of them are known, some (like Skulachev’s ions) are at the research stage, some will be discovered later.

Secondly, it is possible that over time it will be possible to initiate some meiotic processes in somatic cells - for example, in stem and non-dividing cells. I mean those processes that restore the state of the genome: this is apparently the conjugation of homologous chromosomes, crossing over, or something more subtle and still unknown. I see no reason why this would be impossible in principle. In germ cell lines, meiosis is entered into by cells that are, in general, the same in structure as many others. Moreover, even after the conjugation of chromosomes, the activity of the corresponding genes remains in the latter. However, to implement this project, it is necessary to first fully identify the genes responsible for various aspects of meiosis and establish ways to target them. This is, of course, a very fantastic project. However, didn’t much of what we have today seem fantastic yesterday?!

Meiosis, the most important process of cell division that occurs on the eve of the formation of germ cells and was discovered at the end of the 19th century, has long remained the subject of close attention of a very narrow circle of cytologists. It came to the attention of molecular biologists only in the 90s of the 20th century. The rapid development of research in this area was facilitated by work on the molecular genetics of model objects, as well as the emergence of new immunocytochemical methods, which gave researchers a convenient way to study proteins involved in meiosis.

In all eukaryotes, during meiosis, a submicroscopic structure is formed, called synaptonemal complex(from the Greek synaptos - connected, peta - thread). A study of the molecular organization of this complex and its role in meiosis showed that it is needed for the recombination of chromosomes and the reduction of their number. This will be discussed in this article.

But first, let us recall the basic information about meiosis, which consists of two divisions: meiosis I and meiosis II. As a result of reduction division (meiosis I), the number of chromosomes in daughter cells is reduced by half compared to the number of chromosomes in the parent cell. This occurs because the amount of DNA in chromosomes doubles only once before meiosis I (Figure 1). A twofold reduction in the number of chromosomes during the formation of germ cells allows, during fertilization, to restore the original (diploid) number of chromosomes and maintain its constancy. This requires strict separation of pairs of homologous chromosomes between germ cells. When errors occur, aneuploidy occurs - a lack or excess of chromosomes, and this imbalance leads to the death of the embryo or severe developmental abnormalities (in humans, so-called chromosomal diseases).

Structure and function of the synaptonemal complex

The synaptonemal complex consists of two protein axes of homologous chromosomes connected by a protein zipper (Fig. 2). The zipper teeth are rod-shaped dimers of parallel-folded and identically oriented protein molecules with a long α-helix in the middle of the molecule. In yeast S. cerevisiae - this is the protein Zip1, in mammals and humans - SCP1 (SYCP1). These proteins are anchored by their C-terminal ends to the chromosomal axes (lateral elements of the complex), and their N-terminal ends are directed towards each other, inside the central space (Fig. 3). At the N-termini of the molecules there are charged “spurs” - alternating peaks of the densities of positive and negative charges of amino acids (Fig. 4), the complementary interaction of which ensures a strong electrostatic connection of the teeth.

The so-called central space of the complex (the gap between the protein axes, filled with “fastener” teeth, about 100 nm wide), as well as the entire complex (its cross-section is about 150-200 nm) are not visible in a conventional light microscope, since the entire complex is masked by chromatin. For the first time, the synaptonemal complex was observed on ultrathin (0.8 µm thick) sections of crayfish and mouse testes using a transmission electron microscope. It was discovered in 1956 independently by two American researchers - M. Moses and D. W. Fossett.

Now, when studying the complex, the so-called microspreading method is used. Cells of testes (or plant anthers) after hypotonic shock are placed on a plastic substrate applied to a glass slide. The contents of the burst cell are fixed with a weak solution of formaldehyde and contrasted with heavy metal salts (best of all - AgNO 3). The glass is viewed under a phase contrast microscope and the cells that should contain the complex are selected based on indirect evidence. A circle of film with the desired cell is picked up on a metal mesh and placed in an electron microscope (Fig. 5). If necessary, before contrasting, cells are treated with antibodies to proteins of interest to the researcher. These antibodies are labeled with calibrated colloidal gold beads, which are clearly visible under an electron microscope.

During prophase of meiosis I, the synaptonemal complex holds parallel homologous chromosomes almost until they are built at the equator of the cell (metaphase I). Chromosomes are connected using the synaptonemal complex for some time (from 2 hours in yeast to 2-3 days in humans), during which homologous sections of DNA are exchanged between homologous chromosomes - crossing over. Crossing over, which occurs with a frequency of at least one event (usually two, less often three or four) per pair of homologous chromosomes, involves dozens of meiosis-specific enzyme proteins.

The molecular mechanism of crossing over and its genetic consequences are two large topics beyond the scope of this story. We are interested in this process because as a result of it, homologous chromosomes are firmly connected by crossed DNA molecules (chiasmata) and the need for pairwise retention of the chromosome with the help of the synaptonemal complex disappears (after crossing over is completed, the complex disappears). Homologous chromosomes, connected by chiasmata, line up at the equator of the cell division spindle and disperse through the cell division spindle threads into different cells. After meiosis is completed, the number of chromosomes in daughter cells is halved.

So, only on the eve of meiosis I the chromosome structure changes radically. A very specific intranuclear and interchromosomal structure - the synaptonemal complex - appears once in the life cycle of an organism for a short time for pairwise connection of homologous chromosomes and crossing over, and then is dismantled. These and many other events during meiosis at the molecular and subcellular (ultrastructural) levels are ensured by the work of numerous proteins that perform structural, catalytic and kinetic (motor) functions.

Proteins of the synaptonemal complex

Back in the distant 70s, we received indirect evidence that the synaptonemal complex is formed by the self-assembly of its elements, which can occur in the absence of chromosomes. The experiment was carried out by nature itself, and we were able to observe it. It turned out that in the pig roundworm, in the cytoplasm of cells preparing for meiosis I, packages or “stacks” of absolutely correctly arranged morphological elements of the synaptonemal complex appear (although there are no chromosomes in the cytoplasm: they are in the nucleus). Since at the stage of preparation of cells for meiosis there is still no synaptonemal complex in the cell nuclei, there was an assumption that the control of the order of meiotic events in this primitive organism is imperfect. An excess of newly synthesized proteins in the cytoplasm leads to their polymerization and the appearance of a structure not different from the synaptonemal complex. This hypothesis was confirmed only in 2005 thanks to the work of an international group of researchers working in Germany and Sweden. They showed that if the gene encoding the mammalian zipper protein (SCP1) is introduced into somatic cells growing on an artificial nutrient medium and activated, then a powerful network of SCP1 proteins appears inside the cultured cells, “zipped” between itself in the same way as in the central space of the complex. The formation of a layer of continuous protein zippers in cell culture means that our predicted ability of the complex proteins to self-assemble has been proven.

In 1989 and 2001. Our laboratory employees O. L. Kolomiets and Yu. S. Fedotova studied the natural “dismantling” of synaptonemal complexes at the final stages of their existence. This multi-stage process was best observed in pollen mother cells in rye anthers, where there is partial synchrony of meiosis. It turned out that the lateral elements of the complex are dismantled by gradual “unwinding” of the protein superhelix, which has three levels of packaging (Fig. 6).

The basis of the extended lateral elements is a complex of four cohesin proteins (from the English. cohesion— clutch). On the eve of meiosis, a specific cohesin protein, Rec8, appears in the chromosomes, which replaces the somatic cohesin Rad21. Then it is joined by three other cohesin proteins, which are also present in somatic cells, but instead of the somatic cohesin SMC1, the meiosis-specific protein SMC1b appears (its N-terminus is 50% different from the N-terminus of the somatic SMC1 protein). This cohesin complex is located within the chromosome between two sister chromatids, holding them together. Meiosis-specific proteins bind to the cohesin complex, which become major proteins of the chromosomal axes and convert them (these axes) into lateral elements of the synaptonemal complex. In mammals, the major proteins of the synaptonemal complex are SCP2 and SCP3; in yeast, the proteins are Hop1 and Red1, and the meiosis-specific protein is Rec8.

The evolutionary paradox of proteins

In mammals and yeast, the proteins of the synaptonemal complex have different amino acid sequences, but their secondary and tertiary structures are the same. Thus, the zipper protein SCP1 in mammals and the non-homologous protein Zip1 in yeast are built according to a single plan. They consist of three amino acid domains: a central one - an α-helix, capable of forming a second-order helix (supercoiling), and two terminal domains - globules. The major proteins SCP2 and SCP3, which have no homology with the Hop1 and Red1 proteins of yeast and, apparently, with the still insufficiently studied proteins of the complex in plants, also build morphologically and functionally identical structures of the synaptonemal complex. This means that the primary structure (amino acid sequence) of these proteins is an evolutionarily neutral feature.

So, non-homologous proteins in evolutionarily distant organisms build the synaptonemal complex according to a single plan. To explain this phenomenon, I will use an analogy with the construction of houses from different materials, but according to a single plan. It is important that such houses have walls, ceilings, a roof, and that the building materials meet the conditions of strength. Equally, the formation of the synaptonemal complex requires lateral elements (“walls”), transverse filaments (“zipper” teeth) — “overlap” and a central space (room for the “kitchen”). “Kitchen robots” should fit there—complexes of recombination enzymes assembled into so-called “recombination units.”

The width of the central space of the synaptonemal complex in yeast, maize and humans is approximately 100 nm. This is due to the length of single-stranded DNA sections coated with the recombination protein Rad51. This protein belongs to a group of enzymes (similar to the bacterial recombination protein RecA) that have maintained homology since the advent of DNA recombination (approximately 3.5 billion years ago). The inevitability of homology of recombination proteins in distant organisms is determined by their function: they interact with the double helix of DNA (the same in bacteria and mammals), dividing it into single-stranded strands, cover them with a protein cover, transfer one strand to the homologous chromosome and there again restore the double helix. Naturally, most of the enzymes involved in these processes maintain homology for more than 3 billion years. In contrast, synaptonemal complexes, which appeared in eukaryotes after the onset of meiosis (about 850 million years ago), are built from non-homologous proteins... but the scheme of their domain structure is the same. Where did this diagram come from?

A clue is the mentioned Rec8 protein, which begins the formation of chromosomal axes in the meiotic cycle and which is present in all studied organisms. It can be assumed that the building material for the axes of meiotic chromosomes and the lateral elements of the synaptonemal complex can be any intermediate proteins that are capable of forming a fibrous structure (SCP2, Hop1, etc.), interacting with cohesin Rec8 and “precipitating” on it, like concrete on a metal fittings

In recent years, experiencing difficulties in carrying out experimental work due to insufficient funding, we began to actively use bioinformatics methods. We were interested in the zipper protein in Drosophila. Given the similarity of the secondary and tertiary structures of the yeast Zip1 proteins and human SCP1, we hypothesized that the Drosophila zipper protein has the same structure. We began our work in 2001, when the Drosophila genome had already been sequenced and it became known that it contained approximately 13 thousand potential genes. How can we find the gene for the protein we are looking for?

Among the 125 meiosis genes known at that time in Drosophila, we foresaw only one candidate for this role. The fact is that the gene mutation c(3)G deprived chromosomes of the ability to join in pairs using a “zipper” and enter into recombination. We hypothesized that the mutants have a defective protein that forms the submicroscopic teeth of the fastener. The secondary structure and conformation of the desired protein should be similar to the Zip1 and SCP1 proteins.

Knowing that the gene c(3)G is located in Drosophila on chromosome 3, we searched the database for this region (comprising 700 thousand base pairs) for an open reading frame that could encode a similar protein. We understood that in the absence of homology in the primary structure of the desired protein and the yeast protein, their size, organization (of three domains) and the ability of the central domain to form an α-helix of a certain length (about 40 nm) should be similar. This was evidenced by the similarity of the electron microscopic picture of the synaptonemal complex in meiosis in yeast and in Drosophila.

We looked at open reading frames for almost 80 genes in the search area. Using computer programs that make it possible to predict the secondary structure of a virtual protein, its physicochemical properties and the distribution of electrostatic charges in molecules, T. M. Grishaeva found such a reading frame at the border of the gene localization zone c(3)G.(This was not very accurately predicted by Japanese geneticists on a microscopic map of chromosomes.) It turned out to be a gene CG1J604 according to the genomic map of the Selera company.

We concluded that this virtual gene must be a long-known gene c(3)G and encodes a protein similar to the yeast Zip1 protein. In response to our message, we received an email from the USA from S. Hawley. He experimentally proved that the gene c(3)G encodes a protein that forms a "zipper" between chromosomes in meiosis in Drosophila. The results of our work coincided, but the experimental work of Hawley's group took about seven years, and our three-person computer work took only about three months. The articles were published simultaneously. In 2003, we published the method of our computer searches and gave examples of similar virtual proteins in other organisms. This work is now readily cited by foreign colleagues, and our method works successfully in their hands in combination with experimental testing. Thus, in 2005, a group of English biologists discovered the gene and protein of the zipper teeth in the plant Arabidopsis thaliana .

In conclusion, I will give an example of another discovery in the field of molecular biology of meiosis, but we must start with mitosis. In order for the chromatids to separate during anaphase of mitosis, the cohesin that “glues them together” must be destroyed. Hydrolysis of cohesins during mitosis is a genetically programmed event. But in metaphase of meiosis I, when homologous chromosomes are lined up at the equator of the cell and the protein spindle is ready to pull them to the poles, hydrolysis of cohesins turns out to be impossible. That is why both chromatids of each chromosome, glued together in the region of the kinetic center of the chromosomes (kinetochore), are directed to one pole (see Fig. 1). In the late 90s, Japanese researchers, studying meiosis in yeast, found that in the kinetochore region, cohesins are protected by a protein they called shugoshin (the root of this term is taken from the samurai vocabulary and means protection). Very quickly, the global community of meiosis researchers came to the conclusion that similar shugoshin proteins exist in Drosophila, corn, and other objects. Moreover, the genes that “prohibit” the separation of chromatids in meiosis I in Drosophila were known 10 years earlier, but their protein product was not deciphered. And in 2005, a group of American researchers from the University of California at Berkeley, including our compatriot and my longtime colleague in meiosis research I. N. Golubovskaya, reported that during metaphase I of meiosis in maize chromosomes, shugoshin ZmSGO1 is located on both sides of kinetochores, and it appears in this region only if there is already cohesin Rec8 there, which it protects from hydrolysis (but only in meiosis I). These results were obtained using fluorescent antibodies to proteins and a confocal microscope. It remains to be added that Japanese researchers immediately reported that shugoshin protects Rec8 from hydrolysis if shugoshin is dephosphorylated. Phosphorylation and dephosphorylation, as well as acetylation and deacetylation, are important modifications that change the properties of protein molecules.

Application aspect

Everything that has been said is beautiful fundamental science, but is it possible to use this knowledge for practical purposes? Can. Back in the mid-80s, British researchers and our laboratory, using various experimental models, proved that using microspreads of synaptonemal complexes, it is possible to identify twice as many chromosomal rearrangements (deletions, translocations, inversions) compared to the traditional method of chromosome analysis at the metaphase stage (Fig. 7). The fact is that the synaptonemal complex is the skeletal structure of meiotic chromosomes in prophase. At this time, chromosomes are approximately 10 times longer, which significantly increases the resolution of the analysis. However, it is almost impossible to study tangled prophase chromosomes, and the rigid skeletal structures of the synaptonemal complex are not afraid of spreading, and, in addition, an electron microscope is able to distinguish mini-aberrations that are inaccessible to a light microscope.

We asked ourselves: is it possible to establish the cause of sterility in the offspring of irradiated mice by studying not the chromosomes, but the synaptonemal complex? It turned out that in sterile mice that inherited chromosomal translocations from their parents, these rearrangements are detected using the complex in 100% of the cells studied, and with conventional methods of “metaphase” analysis - only in 50% of the cells. A group of Spanish researchers examined more than 1 thousand men suffering from infertility. In a third of them, the cause of infertility could not previously be established, and the study of the synaptonemal complex from the testicular cells of these patients allowed half of them to make a diagnosis: the cause of infertility is the absence of the synaptonemal complex, which is why spermatocytes (sperm precursor cells) do not develop, i.e. e. an “arrest” of the process of meiosis and all spermatogenesis was observed. Similar results were obtained by O. L. Kolomiets together with doctors from Kharkov. The study of the synaptonemal complex in combination with other methods of analysis increases the percentage of identifying the causes of infertility in examined male patients from 17 to 30%. Some English clinics already in the 90s of the XX century. actively used similar methods. Such diagnostics, of course, require high theoretical and practical qualifications of doctors and the use of electron microscopes. Russian laboratories have not yet reached this level, with the exception of the Institute of General Genetics named after. N.I. Vavilova RAS (Moscow) and the Institute of Cytology and Genetics SB RAS (Novosibirsk).

One might think that intensive research into the mechanisms of meiosis will inevitably lead to the application of the acquired knowledge in those areas of biology and medicine that are associated with the fertility of living organisms, including humans. However, the law of applying scientific achievements in practice is unchanged: “implementing” something by force is useless. Practitioners themselves must follow the achievements of science and use them. This is the approach adopted by leading pharmaceutical and biotech firms.

From the discovery of meiosis (1885) to the discovery of the synaptonemal complex (1956) approximately 70 years passed, and from 1956 to the discovery of the proteins of the synaptonemal complex (1986) - another 30. Over the next 20 years, we learned the structure of these proteins, their encoding genes, and interactions proteins in the construction and operation of synaptonemal complexes, in particular, their interaction with DNA recombination enzyme proteins, etc., i.e., more than in the previous 30-year period of descriptive cytological studies. It may take no more than two decades to decipher the basic molecular mechanisms of meiosis. The history of science, like that of all civilization, is characterized by “compression of time,” an increasing compaction of events and discoveries.

Literature:

1. Page S.L., Hawley R.S.// Annu. Rev. Cell Develop. Biol. 2004. V. 20. P. 525-558.
2. Moses M.J.//Chromosoma. 2006. V. 115. P. 152-154.
3. Bogdanov Yu.F.//Chromosoma. 1977. V. 61. P. 1-21.
4. OllingerR. et al.//Moll. Biol. Cell. 2005. V. 16. P. 212-217.
5. Fedotova Y.S. et al. // Genome. 1989. V. 32. P. 816-823; Kolomiets O.L. and etc.// Biological membranes. 2001. T. 18. pp. 230-239.
6. Bogdanov Yu.F. et al. // Int. Review. Cytol. 2007. V. 257. P. 83-142.
7. Bogdanov Yu.F.// Ontogeny. 2004. T. 35. No. 6. pp. 415-423.
8. Grishaeva T.M. et al.// Drosophila Inform. Serv. 2001. V. 84. P. 84-89.
9. Page S.L., Hawley R.S.// Genes Develop. 2001. V. 15. P. 3130-3143.
10. Bogdanov Yu.F. et al. // In Silico Biol. 2003. V. 3. P. 173-185.
11. Osman K. et al. // Chromosoma. 2006. V. 115. P. 212-219.
12. Hamant O., Golubovskaya I. et al.//Curr. Biol. 2005. V. 15. P. 948-954.
13. Kalikinskaya E.I. et al. // Mut. Res. 1986. V. 174. P. 59-65.
14. Egozcue J. et al.//Hum. Genet. 1983. V. 65. P. 185-188; Carrara R. et al.// Genet. Mol. Biol. 2004. V. 27. P. 477-482.
15. Bogdanov Yu.F., Kolomiets O.L. Synaptonemal complex. Indicator of meiosis dynamics and chromosome variability. M., 2007.