Jumping genes

In the middle of the last century, American researcher Barbara McClintock discovered amazing genes in corn that can independently change their position on chromosomes. Now they are called "jumping genes" or transposable (mobile) elements. The discovery was not recognized for a long time, considering mobile elements to be a unique phenomenon, characteristic only for corn. However, it was for this discovery in 1983 that McClintock was awarded Nobel Prize Today, jumping genes have been found in almost all studied animal and plant species.

Where did the hopping genes come from, what do they do in the cell, are there any benefits from them? Why, with genetically healthy parents, the family of the Drosophila fruit fly, due to jumping genes, can produce mutant offspring with a high frequency or even be completely childless? What is the role of jumping genes in evolution?

It must be said that the genes that ensure the functioning of cells are located on the chromosomes in a certain order. Thanks to this, for many types of unicellular and multicellular organisms, it was possible to build the so-called genetic maps. However, there is an order of magnitude more genetic material between genes than in themselves! What role this “ballast” part of DNA plays has not been fully established, but it is here that mobile elements are most often found, which not only move themselves, but can also take neighboring DNA fragments with them.

Where do jumper genes come from? It is believed that at least some of them originate from viruses, since some mobile elements are able to form viral particles (for example, the gipsy mobile element in the fruit fly Drosophila melanogaster). Some transposable elements appear in the genome by the so-called horizontal transfer from other types. For example, it is found that mobile hobo-element (translated into Russian, it is called a tramp) Drosophila melanogaster repeatedly introduced into the genome of this species. There is a version that some regulatory regions of DNA may also have autonomy and a tendency to "vagrancy".

useful ballast

On the other hand, most of the jumping genes, despite the name, behave quietly, although they make up a fifth of the total genetic material. Drosophila melanogaster or almost half of the human genome.

The redundancy of DNA, which was mentioned above, has its own plus: ballast DNA (including passive mobile elements) takes the hit if foreign DNA is introduced into the genome. The likelihood that a new element will be inserted into a useful gene and thereby disrupt its operation is reduced if there is much more bulky DNA than significant.

Some redundancy of DNA is useful in the same way as the "redundancy" of letters in words: we write "Maria Ivanovna" and say "Marivana". Some of the letters are inevitably lost, but the meaning remains. The same principle also works at the level of significance of individual amino acids in a protein-enzyme molecule: only the sequence of amino acids that forms the active center is strictly conservative. Thus, at different levels, redundancy turns out to be a kind of buffer that provides a safety margin for the system. This is how mobile elements that have lost their mobility are not useless for the genome. As they say, “from a thin sheep even a tuft of wool”, although, perhaps, another proverb would be better suited here - “each bast in a line”.

Mobile elements that have retained the ability to jump move along Drosophila chromosomes at a frequency of 10–2–10–5 per gene per generation, depending on the type of element, genetic background, and external conditions. This means that one out of a hundred jumping genes in a cell can change its position after the next cell division. As a result, after several generations, the distribution of transposable elements along the chromosome can change very significantly.

It is convenient to study such a distribution on polytene (multifilamentous) chromosomes from the salivary glands of Drosophila larvae. These chromosomes are many times thicker than normal ones, making it much easier to examine them under a microscope. How are these chromosomes made? In the cells of the salivary glands, the DNA of each of the chromosomes is multiplied, as in normal cell division, but the cell itself does not divide. As a result, the number of cells in the gland does not change, but in 10-11 cycles, several thousand identical DNA strands accumulate in each chromosome.

Partly because of the polytene chromosomes, jumping genes in Drosophila are better understood than in other metazoans. As a result of these studies, it turned out that even within the same Drosophila population it is difficult to find two individuals that have chromosomes with the same distribution of mobile elements. It is no coincidence that most of the spontaneous mutations in Drosophila are believed to be caused by the movement of these "hoppers".

Consequences may vary...

Based on their effect on the genome, active transposable elements can be divided into several groups. Some of them perform functions that are extremely important and useful for the genome. For example, telomeric DNA, located at the ends of chromosomes, in Drosophila just consists of special mobile elements. This DNA is extremely important - the loss of it entails the loss of the entire chromosome in the process of cell division, which leads to cell death.

Other mobile elements are outright "pests". At least they are considered as such this moment. For example, transposable elements of the R2 class can be specifically introduced into arthropod genes that encode one of the proteins of ribosomes - cellular "factories" for protein synthesis. Individuals with such disorders survive only because only a part of the many genes encoding these proteins is damaged in the genome.

There are also such mobile elements that move only in the reproductive tissues that produce germ cells. This is explained by the fact that in different tissues the same mobile element can produce different lengths and functions of the protein-enzyme molecule necessary for movement.

An example of the latter is the P-element Drosophila melanogaster, which got into its natural populations by horizontal transfer from another species of Drosophila no more than a hundred years ago. However, there is hardly a population on Earth right now. Drosophila melanogaster, in which there would be no P-element. At the same time, it should be noted that most of its copies are defective, moreover, the same version of the defect was found almost everywhere. The role of the latter in the genome is peculiar: it is "intolerant" to its fellows and plays the role of a repressor, blocking their movement. So the protection of the Drosophila genome from the jumps of the "alien" can be partially carried out by its own derivatives.

The main thing is to choose the right parents!

Most of the jumps of mobile elements do not affect appearance Drosophila, because it falls on the ballast DNA, but there are other situations when their activity increases dramatically.

Oddly enough, the most powerful factor that induces the movement of jumping genes is poor parenting. For example, what happens if you cross females from a laboratory population Drosophila melanogaster, which do not have a P-element (because their ancestors were caught from nature about a hundred years ago), with males carrying a P-element? In hybrids, due to the rapid movement of the mobile element, a large number of various genetic disorders may appear. This phenomenon, called hybrid dysgenesis, is caused by the absence of a repressor in the maternal cytoplasm that prohibits the movement of the mobile element.

Thus, if grooms from population A and brides from population B can create large families, then the opposite is not always true. A family of genetically healthy parents can produce a large number of mutant or infertile offspring, or even be childless if the father and mother have a different set of mobile elements in the genome. Especially many violations appear if the experiment is carried out at a temperature of 29 ° C. The influence of external factors, superimposed on the genetic background, enhances the effect of genome mismatch, although these factors alone (even ionizing radiation) alone are not capable of causing such a massive movement of mobile elements.

Similar events in Drosophila melanogaster can occur with the participation of other families of mobile elements.

"Mobile" evolution

The cellular genome can be viewed as a kind of ecosystem of permanent and temporary members, where neighbors not only coexist, but also interact with each other. The interaction of host genes with transposable elements is still poorly understood, but many results can be cited - from the death of an organism in the event of damage to an important gene to the restoration of previously damaged functions.

It happens that the jumping genes themselves interact with each other. Thus, a phenomenon resembling immunity is known, when a mobile element cannot be introduced in the immediate vicinity of an existing one. However, not all mobile elements are so delicate: for example, P-elements can easily embed themselves into each other and take their brothers out of the game.

In addition, there is a kind of self-regulation of the number of transposable elements in the genome. The fact is that mobile elements can exchange homologous regions with each other - this process is called recombination. As a result of such interaction, mobile elements may, depending on their orientation, lose ( deletion) or expand ( inversion) fragments of host DNA located between them. If a significant piece of the chromosome is lost, the genome will die. In the case of an inversion or a small deletion, chromosome diversity is created, which is considered a necessary condition for evolution.

If recombinations occur between mobile elements located on different chromosomes, then chromosomal rearrangements are formed as a result, which, during subsequent cell divisions, can lead to an imbalance in the genome. And an unbalanced genome, like an unbalanced budget, is very poorly divided. So the death of unsuccessful genomes is one of the reasons why active transposable elements do not flood chromosomes without limit.

A natural question arises: how significant is the contribution of mobile elements to evolution? First, most of the transposable elements are introduced, roughly speaking, where they have to, as a result of which they can damage or change the structure or regulation of the gene into which they are introduced. Then natural selection sweeps aside unsuccessful options, and successful options with adaptive properties are fixed.

If the consequences of the introduction of a transposable element turn out to be neutral, then this variant can be preserved in the population, providing some diversity in the structure of the gene. This may be useful when adverse conditions. Theoretically, with a massive movement of mobile elements, mutations can appear in many genes at the same time, which can be very useful in a sharp change in the conditions of existence.

So, to summarize: there are many mobile elements in the genome and they are different; they can interact both with each other and with the host genes; can be harmful and irreplaceable. The instability of the genome caused by the movement of mobile elements can end in tragedy for an individual, but the ability to change quickly is a necessary condition for the survival of a population or species. This creates diversity, which is the basis for natural selection and subsequent evolutionary transformations.

You can draw some analogy between jumping genes and immigrants: some immigrants or their descendants become equal citizens, others are given residence permits, and still others - those who do not comply with the laws - are deported or imprisoned. And mass migrations of peoples can quickly change the state itself.

Literature

Ratner V. A., Vasilyeva L. A. Induction of transpositions of mobile genetic elements by stressful influences. Russian binding. 2000.

Gvozdev V. A. Motile eukaryotic DNA // Soros Educational Journal. 1998. No. 8.

On 05/09/2011 at 09:36, Limarev said:

Limarev V.N.

Deciphering the human genome.

Fragment from the book by L.G. Puchko: "Radietic knowledge of man"

To solve the problems of deciphering the genome, the international project "Human Genome" was organized with a budget of billions of dollars.

By 2000, the map of the human genome was practically complete. Genes were counted, identified and recorded in databases. These are huge amounts of information.

Recording the human genome in digitized form takes about 300 terabytes of computer memory, which is equivalent to 3,000 hard drives with a capacity of 100 gigabytes.

It turned out. That a person does not have hundreds of thousands, as previously thought, but a little more than 30 thousand genes. The fly has Drosophila, there are only half as many of them - about 13 thousand, and the mouse has almost the same number as a person. Genes unique to humans in the decoded genome are only about 1%. Most of the DNA helix, as it turned out, is occupied not by genes, but by the so-called “empty sections”, in which genes are simply not encoded, as well as double fragments repeating one after another, the meaning and meaning of which is unclear.

In a word, genes turned out to be not even the bricks of life, but only elements of the blueprint, according to which the building of the organism is built. Bricks, as in other things it was believed before the heyday of genetics, are proteins.

It became absolutely obvious that in 1% of genes unique to humans, such a huge amount of information that distinguishes humans from mice cannot be encoded. Where is all the information stored? For many scientists, it becomes an undoubted fact that without the Divine principle it is impossible to explain the nature of man. A number of scientists suggest that, within the framework of existing ideas about the human body, it is basically impossible to decipher the human genome.

The world is not known - it is knowable (my comments on the article).

1) Consider the fragment: “Without the Divine principle, it is impossible to explain the nature of man.”

The above information does not say anything about this.

The genome, indeed, has a more complex structure than previously thought.

But, after all, the computer mentioned in the article does not consist only of memory cells.

A computer has two memories: long-term and operational, as well as a processor in which information is processed. Participates in the processing of information and the electromagnetic field. In order to decipher the information of the genome, it is necessary to understand how it happens, not only the storage of information, but also its processing. I also admit the idea that part of the information is stored recorded by electromagnetic field. And also outside of a person, as I already wrote, in special information centers of the Higher Mind.

Imagine a continuous text encoded in binary code 0 or 1 of Morse code, while you do not know what language (English or French ....) it is written in, and you do not know that this continuous text consists of words, sentences, paragraphs, chapters, volumes, shelves, cabinets, etc.

It’s almost the same in biology, only everything is encoded here with a four-digit code and we have so far deciphered the order of elementary genes + - / *, but we don’t know the language and, accordingly words, sentences, paragraphs, chapters, volumes, shelves, cabinets, etc. The deciphered genome for us is still a solid text of a 4x cereal code and it is almost impossible to study it all head-on.

But it turns out that at certain times (both in an individual and his cohort of generations and in a species, genus), some genes and their complexes (responsible for words, sentences, paragraphs, chapters, volumes, shelves, cabinets, etc.) are active , and in other periods of evolution they are passive, which I indirectly determined by various polygenic traits (which is shown in the topic The Universal Periodic Law of Evolution).

So far, there are only two methods for studying genes, this is a simple laboratory calculation of the sum of genes (DNA) in a sample and there is a device that counts the amount of RNA produced proteins stuck on the electronic chip generated specific DNA, but since a huge amount of DNA is active at every moment of time and, accordingly, a huge amount of different proteins are produced through RNA, it is very difficult to separate “this noodles with a spoon, fork and Japanese chopsticks” in this soup and find what you are looking for - to find causal relationships between a particular DNA (as a DNA complex) and its influence on a polygenic trait.

It seems that I have found a simple method of how to sort out this whole soup of DNA, RNA and their proteins that determine the degree of a polygenic trait.

As it turned out, each polygenic trait in the order of evolution of an individual (cohorts of generations, species and genus) is periodic, therefore, they must be periodic in RNA and DNA activity, and therefore it is only necessary to find (first going into genetic details) a correlation between the metric change in a polygenic trait (in an individual, a cohort of generations, a species, a genus...) and proportional to these periods, the corresponding activity of RNA, DNA.

Sample of the All-Russian Testing Work in Biology

Grade 11

Work instructions

The test work includes 14 tasks. 1 hour 30 minutes (90 minutes) is allotted to complete the work in biology.

Answers to tasks are a sequence of numbers, a number, a word (phrase) or a short free answer, which is recorded in the place of work designated for this. If you write down an incorrect answer, cross it out and write down a new one next to it.

When completing assignments, you can use a draft. Draft entries do not count towards the assessment of the work. We advise you to complete the tasks in the order in which they are given. To save time, skip the task that you can't complete right away and move on to the next one. If after completing all the work you have time left, you can return to the missed tasks.

The points you get for completed tasks are summed up.

Try to complete as many tasks as possible and score the most points.

Explanations to the sample of the All-Russian verification work

When familiarizing yourself with the sample test work, it should be borne in mind that the tasks included in the sample do not reflect all the skills and content issues that will be tested as part of the All-Russian test work. A complete list of content elements and skills that can be tested in the work is given in the codifier of content elements and requirements for the level of training of graduates for the development of a VWP in biology. The purpose of the sample test work is to give an idea of ​​the structure of the VPR, the number and form of tasks, and the level of their complexity.

1. In the experiment, the experimenter illuminated a part of the drop with amoebas in it. After a short time, the protozoa began to actively move in one direction.

1.1. What property of organisms is illustrated by the experiment?

Explanation: 7 properties of living organisms are distinguished (it is on these grounds that the living differs from the non-living): nutrition, respiration, irritability, mobility, excretion, reproduction, growth. Amoebas from the light part of the drop move to the dark one, as they react to light, that is, we select the property - irritability.

Answer: irritability.

1.2. Give an example of this phenomenon in plants.

Explanation: here we can write any example of a reaction (manifestation of irritability) in plants.

Answer: closing of the trapping apparatus in carnivorous plants OR turning of leaves towards the sun or movement of sunflower during the day after the sun OR bending of stems due to landscape (environment) change.

2. Many plants, animals, fungi and microorganisms live and interact at the edge of the forest. Consider a group that includes a viper, an eagle, a team hedgehog, a viviparous lizard, an ordinary grasshopper. Complete tasks.

2.1. Sign the objects shown in the photographs and the figure that are included in the above group.

1 - viviparous lizard

2 - viper

3 - hedgehog team

4 - common grasshopper

5 - eagle

2.2. List these organisms according to their position in the food chain. In each cell, write down the number or name of one of the objects in the group.

Food chain: hedgehog - common grasshopper - viviparous lizard - viper - eagle.

Explanation: we start the food chain with a producer (a green plant - a producer of organic substances) - a team hedgehog, then, a consumer of the 1st order (consumers consume organic substances and have several orders) - an ordinary grasshopper, a viviparous lizard (consumer of the 2nd order), viper (consumer of the 3rd order), eagle (consumer of the 4th order).

2.3. How will the reduction in the number of hedgehogs of the national team affect the number of eagles? Justify the answer.

Answer: with a reduction in the number of hedgehogs of the team, the number of all subsequent components and, in the end, eagles, decreases, that is, the number of eagles decreases.

3. Consider the figure, which shows a diagram of the carbon cycle in nature. Give the name of the substance marked with a question mark.

Explanation: carbon dioxide (CO2) is indicated by a question mark, since CO2 is formed during combustion, respiration and decomposition of organic substances, and during photosynthesis it is formed (and also dissolves in water).

Answer: carbon dioxide (CO2).

4. Peter mixed equal amounts of the enzyme and its substrate in 25 test tubes. The tubes were left for the same time at various temperatures, the reaction rate was measured. Based on the results of the experiment, Peter built a graph (the x-axis shows the temperature (in degrees Celsius), and the y-axis shows the reaction rate (in arb. units).

Describe the dependence of the enzymatic reaction rate on temperature.

Answer: when the temperature rises to 30 ° C, the reaction rate increases, then it begins to decrease. Optimum temperature - 38C.

5. Set the sequence of subordination of the elements of biological systems, starting with the largest.

Missing items:

1 person

2. Biceps

3. Muscle cell

4. Hand

5. Amino acid

6. Protein actin

Write down the corresponding sequence of numbers.

Explanation: arranges the elements starting from the highest level:

man - organism

hand - organ

biceps - tissue

muscle cell - cellular

actin protein - molecular (proteins are made up of amino acids)

amino acid - molecular

Answer: 142365.

6. Proteins perform many important functions in human and animal organisms: provide the body with building material, are biological catalysts or regulators, provide movement, some transport oxygen. In order for the body not to experience problems, a person needs 100-120 g of proteins per day.

6.1. Using the data in the table, calculate the amount of protein that a person received during dinner if his diet included: 20 g of bread, 50 g of sour cream, 15 g of cheese and 75 g of cod. Round your answer to the nearest integer.

Explanation: 100 g of bread contains 7.8 g of proteins, then 20 g of bread contains 5 times less protein - 1.56 g. 100 g of sour cream contains 3 g of protein, then 50 g is 2 times less - 1.5 100 g of cheese - 20 g of protein, 15 g of cheese - 3 g, 100 g of cod - 17.4 g of protein, 75 g of cod - 13.05 g.

Total: 1.56 + 1.5 + 3 + 13.05 = 19.01 (which is about 19).

Answer: 19

OR

6.1. A person drank a cup of strong coffee containing 120 mg of caffeine, which was completely absorbed and evenly distributed throughout the blood and other body fluids. In the studied person, the volume of body fluids can be considered equal to 40 liters. Calculate how long (in hours) after ingestion caffeine will cease to act on this person if caffeine ceases to act at a concentration of 2 mg / l, and its concentration decreases by 0.23 mg per hour. Round your answer to tenths.

Explanation: 120 mg of caffeine were distributed throughout the human body in a volume of 40 liters, that is, the concentration became 3 mg / l. At a concentration of 2 mg / l, caffeine ceases to act, that is, only 1 mg / l acts. To find out the number of hours, we divide 1 mg / l by 0.23 mg (decrease in concentration per hour), we get 4.3 hours.

Answer: 4.3 hours.

6.2. Name one of the enzymes produced by the glands of the digestive system:

Answer: the walls of the stomach produce pepsin, which breaks down proteins into dipeptides in an acidic environment. Lipase breaks down lipids (fats). Nucleases break down nucleic acids. Amylase breaks down starch. Maltase breaks down maltose into glucose. Lactax breaks down lactose into glucose and galactose. You need to write one enzyme.

7. Determine the origin of the diseases listed. Write down the numbers of each of the diseases in the list in the appropriate cell of the table. Table cells can contain multiple numbers.

List of human diseases:

1. Hemophilia

2. Chickenpox

3. Scurvy

4. Myocardial infarction

5. Cholera

Explanation: See Human Diseases for CDF

8. In medical genetics widely used genealogical method. It is based on the compilation of a person's pedigree and the study of the inheritance of a particular trait. In such studies, certain notations are used. Study a fragment of the family tree of one family, some members of which have a fused earlobe.

Using the proposed scheme, determine whether this trait is dominant or recessive and whether it is linked to the sex chromosomes.

Explanation: the trait is recessive, since in the first generation it does not appear at all, and in the second generation it appears only in 33% of children. The trait is not sex-linked, as it appears in both boys and girls.

Answer: recessive, not sex-linked.

9. Vladimir always wanted to have coarse hair like his dad (dominant trait (A)). But his hair was soft, like his mother's. Determine the genotypes of family members based on hair quality. Record your answers in the table.

Explanation: soft hair is a recessive trait (a), the father is heterozygous for this trait, since the son is homozygous recessive (aa), like the mother. That is:

R: Aa x aa

G: Ah, a ha

F1: Aa - 50% of children with coarse hair

aa - 50% of children with soft hair.

Answer:

10. Ekaterina decided to donate blood as a donor. When taking blood, it turned out that Catherine had the III group. Ekaterina knows that her mother has type I blood.

10.1. What type of blood can Catherine's father have?

Explanation: Based on the data in the table, Catherine's father may have III or IV blood group.

Answer: III or IV.

10.2. Based on the blood transfusion rules, determine if Ekaterina can be a blood donor for her father.

Explanation: Ekaterina with I blood group is a universal donor (provided that the Rh factors match), that is, blood can be transfused from her father.

Answer: maybe.

11. The function of the organoid shown in the figure is the oxidation of organic substances and the storage of energy during the synthesis of ATP. In these processes, the inner membrane of this organoid plays an important role.

11.1. What is the name of this organelle?

Answer: The figure shows a mitochondrion.

11.2. Explain how the packing of the inner membrane in an organoid is related to its function.

Answer: with the help of the folds of the inner membrane, it increases the inner surface of the organoid and more organic substances can be oxidized, as well as more ATP can be produced on ATP synthases - enzymatic complexes that produce energy in the form of ATP (the main energy molecule).

12. An mRNA fragment has the following sequence:

UGTSGAAUGUUUGTSUG

Determine the sequence of the DNA region that served as a template for the synthesis of this RNA molecule, and the protein sequence that is encoded by this mRNA fragment. When completing the task, use the rule of complementarity and the table of the genetic code.

Rules for using the table

The first nucleotide in the triplet is taken from the left vertical row; the second - from the upper horizontal row and the third - from the right vertical. Where the lines coming from all three nucleotides intersect, the desired amino acid is located.

Explanation: let's divide the sequence into triplets (three nucleotides each): UGC GAA UGU UUG CUG. Let's write down the corresponding nucleotide sequence in DNA (reverse complementary nucleotide sequence, given that A-T (in RNA Y), G-C.

That is, the DNA chain: ACG CTT ACA AAU GAU.

Find the corresponding amino acid sequence from the RNA sequence. The first amino acid is cis, then glu, cis, leu, lei.

Protein: cis-glu-cis-ley-ley.

12.3. When deciphering the tomato genome, it was found that the proportion of thymine in a fragment of a DNA molecule is 20%. Using the Chargaff rule, which describes the quantitative ratios between different types of nitrogenous bases in DNA (G + T = A + C), calculate the amount (in%) in this sample of nucleotides with cytosine.

Explanation: if the amount of thymine is 20%, then the amount of adenine is also 20% (since they are complementary). 60% remains for guanine and cytosine (100 - (20 + 20)), that is, 30% each.

Answer: 30% is cytosine.

13. Modern evolutionary theory can be represented as the following diagram.

Answer: probably the ancestors of the giraffe had different neck lengths, but since giraffes needed to reach high-growing green leaves, only giraffes with a long neck, that is, the most adapted, survived (this trait was attached from generation to generation, this led to a change in the genetic composition of the population ). Thus, in the course of natural selection, only individuals with the longest neck survived, and the length of the neck gradually increased.

14. The figure shows cordaite - an extinct woody gymnosperm that lived 370-250 million years ago.

Using a fragment of a geochronological table, determine the era and periods in which this organism lived. What plants were their possible ancestors?

Geological table

Explanation: gymnosperms probably appeared in the Paleozoic era. periods: Perm, Carboniferous (possibly Devon). They arose from tree-like ferns (more primitive plants flourished in the Paleozoic era, and gymnosperms spread widely and flourished in the Mesozoic era).

Era: Paleozoic

Periods: Perm, Carboniferous, Devon

Possible ancestors: tree ferns

2 018 federal Service for Supervision in the Sphere of Education and Science of the Russian Federation

completely defined. Therefore, the work on deciphering the nematode genome should be recognized as very successful.

Even greater success is associated with the decoding of the Drosophila genome, only in

2 times smaller than human DNA and 20 times larger than nematode DNA. Despite the high degree of genetic knowledge of Drosophila, about 10% of its genes were unknown until that moment. But the most paradoxical is the fact that the Drosophila, much more highly organized than the nematode, turned out to have fewer genes than the microscopic roundworm! It is difficult to explain from modern biological positions. More genes than in Drosophila are also present in the decoded genome of a plant from the cruciferous family - Arabidopsis, widely used by geneticists as a classic experimental object.

The development of genomic projects was accompanied by the intensive development of many areas of science and technology. So, bioinformatics received a powerful impetus for its development. A new one was created mathematical apparatus for storing and processing huge amounts of information; supercomputer systems with unprecedented power have been designed; thousands of programs have been written that allow in a matter of minutes to conduct a comparative analysis of various blocks of information, daily enter new data into computer databases,

obtained in various laboratories around the world, and adapt new information to that which has been accumulated previously. At the same time, systems were developed for effective isolation various elements genome and automatic sequencing, that is, the determination of DNA nucleotide sequences. On this basis, powerful robots have been designed that significantly speed up sequencing and make it less expensive.

The development of genomics, in turn, has led to the discovery of a huge number of new facts. The significance of many of them has yet to be assessed in

the future. But even now it is obvious that these discoveries will lead to a rethinking of many theoretical positions regarding the emergence and evolution of various forms of life on Earth. They will contribute to a better understanding of the molecular mechanisms underlying the functioning of individual cells and their interactions; detailed deciphering of many hitherto unknown biochemical cycles;

analysis of their connection with fundamental physiological processes.

Thus, there is a transition from structural genomics to

functional, which in turn creates the prerequisites for

studies of the molecular basis of the work of the cell and the organism as a whole.

The information already accumulated will be the subject of analysis during

the next few decades. But every next step in

direction of deciphering the structure of genomes different types, generates new technologies that facilitate the process of obtaining information. So,

using data on the structure and function of the genes of lower organized species of living beings can significantly speed up the search

displace rather time-consuming molecular methods of gene search.

The most important consequence of deciphering the structure of the genome of a particular species is the ability to identify all its genes and,

respectively, identification and determination of the molecular nature of the transcribed RNA molecules and all its proteins. By analogy with the genome, the concepts of transcriptome, which unites the pool of RNA molecules formed as a result of transcription, and proteome, which includes many proteins encoded by genes, were born. Thus, genomics creates the foundation for the intensive development of new sciences - proteomics and transcriptomics. Proteomics deals with the study of the structure and function of each protein; analysis of the protein composition of the cell; determination of the molecular basis of the functioning of a single cell, which is

the result of the coordinated work of many hundreds of proteins, and

study of the formation of the phenotypic trait of an organism,

which is the result of the coordinated work of billions of cells.

Very important biological processes also occur at the RNA level. Their analysis is the subject of transcriptomics.

The greatest efforts of scientists from many countries of the world working in the field of genomics were aimed at solving the international project "Human Genome". Significant progress in this area is associated with the implementation of the idea,

proposed by J. S. Venter, to search and analyze

expressed DNA sequences, which can later be used as a kind of "labels" or markers of certain parts of the genome. Another independent and no less fruitful approach was taken by the work of the group headed by Fr.

Collins. It is based on the primary identification of genes for human hereditary diseases.

Deciphering the structure of the human genome led to a sensational discovery. It turned out that the human genome contains only 32,000 genes, which is several times less than the number of proteins. At the same time, there are only 24,000 protein-coding genes; the products of the remaining genes are RNA molecules.

The percentage of similarity in DNA nucleotide sequences between different individuals, ethnic groups and races is 99.9%.

This similarity is what makes us human - Homo sapiens! All our variability at the nucleotide level fits into a very modest figure - 0.1%.

Thus, genetics leaves no room for ideas of national or racial superiority.

But, look at each other - we are all different. National, and even more so, racial differences are even more noticeable. So how many mutations determine the variability of a person not in percentage terms, but in absolute terms? In order to get this estimate, you need to remember what the size of the genome is. The length of a human DNA molecule is

3.2x109 base pairs. 0.1% of this is 3.2 million nucleotides. But remember that the coding part of the genome occupies less than 3% of the total length of the DNA molecule, and mutations outside this region, most often, do not have any effect on phenotypic variability. Thus, to obtain an integral estimate of the number of mutations that affect the phenotype, you need to take 3% of 3.2 million nucleotides, which will give us a figure of the order of 100,000. That is, about 100 thousand mutations form our phenotypic variability. If we compare this figure with total number genes, it turns out that on average there are 3-4 mutations per gene.

What are these mutations? The vast majority (at least 70%)

determines our individual non-pathological variability, what distinguishes us, but does not make us worse in relation to each other. This includes features such as eye, hair, skin color, body type, height, weight,

a type of behavior that is also largely genetically determined, and much more. About 5% of mutations are associated with monogenic diseases. About a quarter of the remaining mutations belong to the class of functional polymorphisms. They are involved in the formation of hereditary predisposition to widespread multifactorial pathology. Of course, these estimates are rather rough.

but they allow us to judge the structure of human hereditary variability.

Chapter 1.16. Molecular genetic foundations of evolution

The revolution in molecular biology that took place at the turn of the millennium, culminating in the deciphering of the structure of the genomes of many hundreds of species of microorganisms, as well as some types of protozoa,

yeast, plants, animals and humans, turned many of the traditional ideas of classical genetics and brought closer the possibility of studying the molecular mechanisms of evolution and speciation. A new science was born - comparative genomics,

allowing to register the appearance in various phylogenetic lines of evolutionarily significant events occurring at the level of individual molecules. It turned out that, in the general case, evolutionary progress is associated not only, and not so much with an increase in the number, length, and even complexity of the structural organization of genes, but to a much greater extent with a change in the regulation of their work, which determines the coordination and tissue-specific expression of tens of thousands of genes. Ultimately, this led to the appearance in higher organisms of more complex, highly specific, multifunctional complexes of interacting proteins capable of performing fundamentally new tasks.

Let's consider the nature of changes occurring in the process of evolution at three information levels: DNA - RNA - protein or genome - transcriptome - proteome. In general, we can say that as the complexity of the organization of life increases, the size of the genome increases. Thus, the size of prokaryotic DNA does not exceed 8x106 bp, it becomes twice as large in yeast and protozoa, 10-15 times as large in insects, and in mammals the increase reaches 3 orders of magnitude, that is, a thousand times (103).

However, this relationship is not linear. So within mammals, we no longer see a significant increase in genome size. In addition, it is not always possible to observe the relationship between the size of the genome and the complexity of the organization of life. Thus, in some plants, the size of the genome is an order of magnitude or even two orders of magnitude larger than in humans. Recall that the increase in the size of the eukaryotic genome compared to prokaryotes occurs mainly due to the appearance of non-coding sequences, that is, optional elements. We have already said that in the human genome, exons in total amount to no more than 1-3%. And this means that the number of genes in higher organisms can be only several times greater than in microorganisms.

The increase in the complexity of eukaryotic organization is partly due to the emergence of an additional regulatory system necessary for

ensuring tissue-specific gene expression. One of the consequences of the discontinuous organization of genes that arose in eukaryotes was the widespread use of alternative splicing and alternative transcription. This led to the emergence of a new property in a huge number of genes - the ability to encode multiple functionally different protein isoforms. Thus, the total amount of proteins

that is, the size of the proteome, higher ones can have several times more genes.

In prokaryotes, intraspecific variability in the number of genes is acceptable, and

similar differences between different strains of many microorganisms, in

including pathogens, can be tens of percent. However, the complexity of the organization various kinds microorganisms directly correlates with the number and length of coding sequences.

Thus, phenotypic intra- and interspecies variability is in strict association with the sizes of the transcriptome and proteome, which are very similar in their values. In eukaryotes, the number of genes is a rigidly determined species trait, and the increase in evolutionary complexity is based on a different principle—differential multilevel use of various components of a limited and fairly stable proteome.

Sequencing of the nematode and Drosophila genomes has shown that the proteome sizes in these very different species are very close and only twice as large as in yeast and some bacterial species. This regularity—a significant increase in the complexity of organizing various forms of life while maintaining or relatively slightly increasing the size of the proteome—is characteristic of all subsequent evolution up to man. So,

human and mouse proteomes practically do not differ from each other and are less than 2 times larger than the proteomes of the nematode microscopic round worm or Drosophila fruit fly. Moreover, the identity of the nucleotide sequences of human DNA and

great African monkeys is 98.5%, and in coding areas reaches 99%. These figures differ little from the value of 99.9%,

determining intraspecific similarity in DNA nucleotide sequences between different individuals, peoples and races inhabiting our planet. So what are the key changes that make up no more than 1.5% of the entire genome for the formation of a person? The answer to this question, apparently, should be sought not only at the genomic and proteomic levels.

Indeed, along with the relative stability of the proteome, in

In the process of evolution, there is a sharp increase in the size and complexity of the organization of the eukaryotic transcriptome due to the appearance in the genome of a huge amount of transcribed and non-coding DNA, as well as a significant expansion of the class of RNA-coding genes. RNAs that do not code for proteins, the main source of which are introns,

make up the vast majority of the transcriptome of higher organisms,

reaching 97-98% of all transcription units. At present, the functions of these molecules are being intensively analyzed.

Thus, the key evolutionary changes occur against the background of an increase in the size of the genome, a fairly stable proteome, and a sharp increase in the size of the transcriptome (Fig. 31.

Figure 31. Evolutionary changes taking place on three

information levels At the same time, the transition from simple forms of life to more complex ones is obviously

correlates with the occurrence and widespread in the genome of two fundamental and to some extent interconnected evolutionary acquisitions: non-coding DNA and repetitive elements. A direct consequence of these changes occurring at the genomic level is the appearance in the process of evolution of a huge number of RNAs that do not code for proteins.

What is the structural basis of these evolutionary transformations?

All major evolutionary transitions: from prokaryotes to eukaryotes, from protozoans to multicellular organisms, from the first animals to bilaterals, and from primitive chordates to vertebrates, were accompanied by a sharp increase in the complexity of the genome. Apparently, such jumps in evolution are the result of rare cases of successful fusion of entire genomes of various species belonging to systematic classes that diverged at a considerable distance from each other. Thus, the symbiosis of Archaea and Bacteria marked the beginning of the transition from prokaryotes to eukaryotes. Obviously, mitochondria, chloroplasts, and some other cell organelles also appeared as a result of endosymbiosis. The fundamental property of higher eukaryotes, diploidy, arose from a well-regulated genomic duplication that occurred about 500 million years ago.

Genomic duplications within a species occurred quite often, and

examples of this are the numerous cases of polyploidy in plants,

fungi and sometimes even animals. However, potential mechanisms

leading to the emergence in the process of evolution of fundamentally new forms of life are not autopolyploidy, but hybridization and horizontal transfer or fusion of genomes. It is noteworthy that the most significant evolutionary transformations, accompanied by the fusion of entire genomes, occur under extraordinary conditions, during periods of major geological transitions, such as changes in atmospheric oxygen concentration, glaciation of the Earth, or the Cambrian explosion.

In relatively calm geological conditions, duplications of individual genes or chromosome segments with their subsequent divergence turn out to be more significant for evolution. Comparison of the nucleotide sequences of sequenced genomes shows that the frequency of gene duplications is quite high and, on average, is 0.01 per gene per million years. The vast majority of them do not manifest themselves over the next several million years, and only in rare cases

cases, duplicated genes can acquire new adaptive functions. Nevertheless, a large class of "silent" gene duplications serves as a kind of reserve fund for the birth of new genes and the formation of new species. The human genome contains from 10,000 to 20,000 copies of processed genes that have arisen by mRNA retroposition.

Most of them belong to the class of pseudogenes, that is, they are not expressed either due to the presence of mutations or due to insertion into transcriptionally inactive regions of the genome. However, some of these genes are active, and the nature of their expression and even functions may be different,

than founding genes.

A special role in the evolution of primates and humans is played by segmental duplications belonging to the class of low-copy repeats (LCR) and

originated less than 35 million years ago. These sequences are highly identical blocks of DNA, varying in size from one to several hundred kilobases. Most often, segmental duplications are localized in the pericentromeric or telomeric regions of different chromosomes, and in total they occupy about 5% of the human genome.

No segmental duplications were found in other sequenced genomes.

The smallest unit of segmental duplication, called a duplicon, contains fragments of unrelated unprocessed genes, and

this distinguishes it from other known types of repeating sequences. Under certain conditions, duplicons can serve as sources for the creation of new chimeric transcribed genes or gene families from various combinations of coding exons present in them. According to some estimates, between 150 and 350 genes can distinguish between chimpanzee and human genomes.

Without belittling the importance for speciation of the facts of the appearance of new and disappearance of old coding sequences, one should emphasize the real possibility of the existence of other mechanisms,

playing a decisive role in the evolution of eukaryotes.

One of the driving mechanisms of evolution is mobile elements found in all species studied in this regard.

Genome changes that accompany the process of speciation may include extensive karyotype reorganizations, local chromosomal rearrangements, duplications of gene families, modifications of individual genes,

accompanied by their birth or loss, as well as differences in gene expression, regulated both at the level of transcription and at the levels of splicing or translation. Mobile elements are directly related to all these processes.

In some cases, transposable elements themselves carry sequences encoding enzymes whose presence is required to effect DNA transposition or RNA retroposition.

Similar sequences are present in the genome of retroviruses, LTR-

elements and transposons. The most numerous class of transposable elements, Alu-repeats, also belongs to the group of retrotransposons. For the first time Alu-

repeats appear in primates about 50-60 million years ago from a small RNA-coding gene. In the process of further evolution, divergence and powerful amplification of this family occur. The transition from primates to humans is accompanied by an explosive increase in the number

Alu-repeats, the number of copies of which, according to some estimates, reaches

1.1 million. Alu repeats occupy about 10% of the human genome, but their distribution is uneven, since they are more associated with genes. These elements are rarely present in coding exons and are often found in introns and non-coding regions of mRNA to affect the stability of these molecules and/or the efficiency of translation. The presence of Alu sequences in the intron regions of genes may be accompanied by a change in the nature of preRNA processing, since these sequences contain regions homologous to donor and acceptor splicing sites. Insertion of Alu-elements into the regulatory regions of the gene may disrupt transcription, resulting in