The mechanism of inheritance of linked genes, as well as the location of some linked genes, was established by the American geneticist and embryologist T. Morgan. He showed that the law of independent inheritance formulated by Mendel is valid only in cases where genes carrying independent characteristics are localized on different non-homologous chromosomes. If the genes are located on the same chromosome, then the inheritance of traits occurs jointly, i.e. linked. This phenomenon came to be called linked inheritance, as well as the law of linkage or Morgan's law.

The law of adhesion says: linked genes located on the same chromosome are inherited together (linked). Clutch group- all genes on one chromosome. The number of linkage groups is equal to the number of chromosomes in the haploid set. For example, a person has 46 chromosomes - 23 linkage groups, a pea has 14 chromosomes - 7 linkage groups, and the fruit fly Drosophila has 8 chromosomes - 4 linkage groups. Incomplete gene linkage- the result of crossing over between linked genes, That's why complete gene linkage perhaps in organisms in whose cells crossing over does not normally occur.

MORGAN'S CHROMOSOME THEORY. BASIC PROVISIONS.

The result of T. Morgan’s research was the creation of a chromosomal theory of heredity:

1) genes are located on chromosomes; different chromosomes contain different numbers of genes; the set of genes of each of the non-homologous chromosomes is unique;

2) each gene has a specific location (locus) in the chromosome; allelic genes are located in identical loci of homologous chromosomes;

3) genes are located on chromosomes in a certain linear sequence;

4) genes localized on the same chromosome are inherited together, forming a linkage group; the number of linkage groups is equal to the haploid set of chromosomes and is constant for each type of organism;

5) the linkage of genes can be disrupted during the process of crossing over, which leads to the formation of recombinant chromosomes; the frequency of crossing over depends on the distance between genes: the greater the distance, the greater the magnitude of crossing over;

6) each species has a unique set of chromosomes - a karyotype.

Sex-linked inheritance- This is the inheritance of a gene located on the sex chromosomes. With heredity associated with the Y chromosome, the symptom or disease manifests itself exclusively in the male, since this sex chromosome is not present in the female chromosome set. X-linked inheritance can be dominant or recessive in females, but it is always present in males because there is only one X chromosome. Sex-linked inheritance of the disease is mainly associated with the sex X chromosome. Most hereditary diseases (certain pathological characteristics) associated with gender are transmitted recessively. There are about 100 such diseases. A woman who is a carrier of a pathological trait does not herself suffer, since the healthy X chromosome dominates and suppresses the X chromosome with the pathological trait, i.e. compensates for the inferiority of this chromosome. In this case, the disease manifests itself only in males. The X-linked recessive type transmits: color blindness (red-green blindness), optic nerve atrophy, night blindness, Duchenne myopia, “curly hair” syndrome (occurs as a result of impaired copper metabolism, increased copper content in tissues, manifests itself as slightly colored , sparse and falling hair, mental retardation, etc.), a defect in the enzymes that convert purine bases into nucleotides (accompanied by a violation of DNA synthesis in the form of Lesch-Nyen syndrome, manifested by mental retardation, aggressive behavior, self-mutilation), hemophilia A (as a result of a deficiency antihemophilic globulin - factor VIII), hemophilia B (as a result of deficiency of the Christmas factor - factor IX), etc. The dominant X-linked type transmits hypophosphatemic rickets (which cannot be treated with vitamins D2 and D3), brown tooth enamel, etc. These diseases develop in both males and females.

Complete and incomplete gene linkage.

Genes on chromosomes have different strengths of cohesion. The linkage of genes can be: complete, if recombination is impossible between genes belonging to the same linkage group; and incomplete, if recombination is possible between genes belonging to the same linkage group.

Genetic maps of chromosomes.

These are diagrams of the relative location of interlocking

hereditary factors - genes. G.K.H. display realistically

the existing linear order of gene placement on chromosomes (see Cytological maps of chromosomes) and are important both in theoretical research and in breeding work, because make it possible to consciously select pairs of traits during crossings, as well as predict the characteristics of inheritance and manifestation of various traits in the organisms being studied. Having G. ch., it is possible, by inheriting a “signal” gene that is closely linked to the one being studied, to control the transmission to offspring of genes that determine the development of difficult-to-analyze traits; for example, the gene that determines the endosperm in corn and is located on chromosome 9 is linked to the gene that determines reduced plant viability.

85. Chromosomal mechanism of sex inheritance. Cytogenetic methods for determining sex.

Floor characterized by a complex of characteristics determined by genes located on chromosomes. In species with dioecious individuals, the chromosomal complex of males and females is not the same; cytologically they differ in one pair of chromosomes, it was called sex chromosomes. The identical chromosomes of this pair were called X(x)-chromosomes . Unpaired, absent from the other sex - Y (Y) - chromosome ; the rest, for which there are no differences autosomes(A). Humans have 23 pairs of chromosomes. Of them 22 pairs of autosomes and 1 pair of sex chromosomes. A sex with identical XX chromosomes that forms one type of gamete (with an X chromosome) is called homogametic, different sex, with different XY chromosomes, forming two types of gametes (with an X chromosome and with a Y chromosome), - heterogametic. In humans, mammals and other organisms heterogametic sex male; in birds and butterflies - female.

X chromosomes, in addition to the genes that determine female, contain genes that are not related to gender. Traits determined by chromosomes are called gender-linked characteristics. In humans, such signs are color blindness (color blindness) and hemophilia (incoagulability of the blood). These anomalies are recessive; women do not show such signs, even if these genes are carried by one of the X chromosomes; such a woman is a carrier and passes them on with the X chromosome to her sons.

Cytogenetic method of sex determination. It is based on the microscopic study of chromosomes in human cells. The use of the cytogenetic method allows not only to study the normal morphology of chromosomes and the karyotype as a whole, to determine the genetic sex of the organism, but, most importantly, to diagnose various chromosomal diseases associated with changes in the number of chromosomes or a violation of their structure. As a rapid method that detects changes in the number of sex chromosomes, they use method for determining sex chromatin in non-dividing cells of the buccal mucosa. Sex chromatin, or Barr body, is formed in the cells of the female body on one of the two X chromosomes. With an increase in the number of X chromosomes in the karyotype of an organism, Barr bodies are formed in its cells in an amount one less than the number of chromosomes. When the number of chromosomes decreases, the body is absent. In the male karyotype, the Y chromosome can be detected by more intense luminescence compared to other chromosomes when they are treated with acryquiniprite and studied under ultraviolet light.

Features of the structure of chromosomes. Levels of organization of hereditary material. Hetero- and euchromatin.

Chromosome morphology

Microscopic analysis of chromosomes, first of all, reveals their differences in shape and size. The structure of each chromosome is purely individual. It can also be noted that the chromosomes have common morphological characteristics. They consist of two threads - chromatid, located parallel and connected to each other at one point, called the centromere or primary constriction. On some chromosomes you can also see a secondary constriction. It is a characteristic feature that allows one to identify individual chromosomes in a cell. If the secondary constriction is located close to the end of the chromosome, then the distal region limited by it is called a satellite. Chromosomes containing a satellite are referred to as AT chromosomes. In some of them, nucleoli are formed during telophase.
The ends of chromosomes have a special structure and are called telomeres. Telomeric regions have a certain polarity that prevents them from connecting to each other during breaks or with free ends of chromosomes.

The section of the chromatid (chromosome) from the telomere to the centromere is called the chromosome arm. Each chromosome has two arms. Depending on the ratio of arm lengths, three types of chromosomes are distinguished: 1) metacentric (equal arms); 2) submetacentric (unequal shoulders); 3) acrocentric, in which one shoulder is very short and is not always clearly distinguishable. (p - short arm, q - long arm). A study of the chemical organization of chromosomes in eukaryotic cells has shown that they consist mainly of DNA and proteins: histones and protomite (in germ cells), which form a nucleoprotein complex called chromatin, which received its name for its ability to be stained with basic dyes. Proteins make up a significant part of the substance of chromosomes. They account for about 65% of the mass of these structures. All chromosomal proteins are divided into two groups: histones and non-histone proteins.
Histones represented by five fractions: HI, H2A, H2B, NZ, H4. Being positively charged basic proteins, they bind quite firmly to DNA molecules, which prevents the reading of the biological information contained in it. This is their regulatory role. In addition, these proteins perform a structural function, ensuring the spatial organization of DNA in chromosomes.

Number of factions non-histone proteins exceeds 100. Among them are enzymes for RNA synthesis and processing, DNA reduplication and repair. Acidic proteins of chromosomes also perform structural and regulatory roles. In addition to DNA and proteins, chromosomes also contain RNA, lipids, polysaccharides, and metal ions.

1) Genes are located on chromosomes.

2) Genes on chromosomes are located linearly one after another and do not overlap.

3) Genes located on the same chromosome are called linked and form a linkage group. Since homologous chromosomes include allelic genes responsible for the development of the same traits, both homologous chromosomes are included in the linkage group; thus, the number of linkage groups corresponds to the number of chromosomes in the haploid set. Within each linkage group, recombination of genes occurs due to crossing over.

4) Morgan's Law - “Genes located on the same chromosome are inherited together.”

Complete gene linkage. If genes are located directly next to each other on a chromosome, then crossing over between them is almost impossible. They are almost always inherited together, and in test crossings a 1:1 split is observed.

Incomplete gene linkage. If genes on chromosomes are located at a certain distance from each other, then the frequency of crossing over between them increases and, consequently, crossover chromosomes appear that carry new combinations of genes: Ab and aB

Their number is directly proportional to the distance between genes. When linkage is incomplete, a certain number of crossover forms appear in the offspring, and their number depends on the distance between the genes. The percentage of crossover forms indicates the distance between genes located on the same chromosome.

Non-allelic gene interactions

Complementarity is a phenomenon in which the gene of one allelic pair contributes to the manifestation of the genes of another allelic pair.

1) Sweet peas have gene A, which determines the synthesis of a colorless pigment precursor - propigment. Gene B determines the synthesis of an enzyme, under the action of which pigment is formed from propigment. Flowers of sweet peas with genotypes aaBB and Aabb are white: in the first case there is an enzyme, but no propigment, in the second there is a propigment. but there is no enzyme that converts propigment into pigment:

2) New development of the trait - inheritance of the shape of the comb in chickens of some breeds. As a result of different combinations of genes, four variants of comb shape arise:

Fig. The shape of the crest of roosters: A – simple (aabb); B – pisiform (aaBB or aaBB); B – nut-shaped (AABB or AaBb); G – pinkish (ААБ or Aabb)

Epistasis is a phenomenon in which the gene of one allelic pair prevents the expression of genes from another allelic pair, for example, the development of fruit color in a pumpkin. Pumpkin fruits will be colored only if the plant genotype lacks the dominant gene B from another allelic pair. This gene suppresses the development of color in pumpkin fruits, and its recessive allele b does not prevent color development (Aabb - yellow fruits; aabb - green fruits; AABB and aaBB - white fruits).

Polymerism is a phenomenon in which the degree of expression of a trait depends on the action of several different pairs of allelic genes, and the more dominant genes of each pair are in the genotype, the more pronounced the trait. In wheat, the red color of grains is determined by two genes: a1, a2;. Non-allelic genes are designated here by one letter A(a) because they determine the development of one trait. With the A1A1A2A2 genotype, the color of the grains is the most intense; with the A1A1A2A2 genotype, they are white. Depending on the number of dominant genes in the genotype, all transitions between intense red and white color can be obtained:

Rice. 26. Inheritance of the color of wheat grains (polymerism)

Chained inheritance. Chromosomal theory of heredity.

Chromosomal theory of heredity.

Basic provisions of the chromosomal theory of heredity. Chromosomal analysis.

Formation of the chromosome theory. In 1902-1903 American cytologist W. Setton and German cytologist and embryologist T. Boveri independently identified parallelism in the behavior of genes and chromosomes during the formation of gametes and fertilization. These observations formed the basis for the assumption that genes are located on chromosomes. However, experimental evidence of the localization of specific genes on specific chromosomes was obtained only in 1910 by the American geneticist T. Morgan, who in subsequent years (1911-1926) substantiated the chromosomal theory of heredity. According to this theory, the transmission of hereditary information is associated with chromosomes, in which genes are localized linearly, in a certain sequence. Thus, it is chromosomes that represent the material basis of heredity.

Chromosomal theory of heredity- the theory according to which chromosomes contained in the cell nucleus are carriers of genes and represent the material basis of heredity, that is, the continuity of the properties of organisms in a number of generations is determined by the continuity of their chromosomes. The chromosomal theory of heredity arose at the beginning of the 20th century. based on cell theory and was used to study the hereditary properties of organisms through hybridological analysis.

Basic provisions of the chromosomal theory of heredity.

1. Genes are localized on chromosomes. Moreover, different chromosomes contain an unequal number of genes. In addition, the set of genes of each of the non-homologous chromosomes is unique.

2. Allelic genes occupy identical loci on homologous chromosomes.

3. Genes are located on the chromosome in a linear sequence.

4. Genes on one chromosome form a linkage group, that is, they are inherited predominantly linked (together), due to which linked inheritance of some traits occurs. The number of linkage groups is equal to the haploid number of chromosomes of a given species (in the homogametic sex) or greater by 1 (in the heterogametic sex).

5. Linkage is broken as a result of crossing over, the frequency of which is directly proportional to the distance between genes on the chromosome (therefore, the strength of linkage is inversely related to the distance between genes).

6. Each biological species is characterized by a certain set of chromosomes - a karyotype.

Chained inheritance

Independent combination of traits (Mendel's third law) is carried out under the condition that the genes that determine these traits are located in different pairs of homologous chromosomes. Consequently, in each organism the number of genes that can be independently combined in meiosis is limited by the number of chromosomes. However, in an organism the number of genes significantly exceeds the number of chromosomes. For example, before the era of molecular biology, more than 500 genes were studied in corn, more than 1 thousand in the Drosophila fly, and about 2 thousand genes in humans, while they have 10, 4 and 23 pairs of chromosomes, respectively. The fact that the number of genes in higher organisms is several thousand was already clear to W. Sutton at the beginning of the 20th century. This gave reason to assume that many genes are localized on each chromosome. Genes located on the same chromosome form a linkage group and are inherited together.

T. Morgan proposed to call the joint inheritance of genes linked inheritance. The number of linkage groups corresponds to the haploid number of chromosomes, since the linkage group consists of two homologous chromosomes in which the same genes are localized. (In individuals of the heterogametic sex, such as male mammals, there are actually one more linkage groups, since the X and Y chromosomes contain different genes and represent two different linkage groups. Thus, women have 23 linkage groups, and for men - 24).

The mode of inheritance of linked genes differs from the inheritance of genes localized in different pairs of homologous chromosomes. Thus, if, with independent combination, a diheterozygous individual forms four types of gametes (AB, Ab, aB and ab) in equal quantities, then with linked inheritance (in the absence of crossing over), the same diheterozygote forms only two types of gametes: (AB and ab) also in equal quantities. The latter repeat the combination of genes in the parent's chromosome.

It was found, however, that in addition to ordinary (non-crossover) gametes, other (crossover) gametes also arise with new combinations of genes—Ab and aB—that differ from the combinations of genes in the parent’s chromosomes. The reason for the appearance of such gametes is the exchange of sections of homologous chromosomes, or crossing over.

Crossing over occurs in prophase I of meiosis during the conjugation of homologous chromosomes. At this time, parts of two chromosomes can cross over and exchange their sections. As a result, qualitatively new chromosomes appear, containing sections (genes) of both maternal and paternal chromosomes. Individuals that are obtained from such gametes with a new combination of alleles are called crossing over or recombinant.

The frequency (percentage) of crossover between two genes located on the same chromosome is proportional to the distance between them. Crossing over between two genes occurs less often the closer they are located to each other. As the distance between genes increases, the likelihood that crossing over will separate them on two different homologous chromosomes increases.

The distance between genes characterizes the strength of their linkage. There are genes with a high percentage of linkage and those where linkage is almost undetectable. However, with linked inheritance, the maximum frequency of crossing over does not exceed 50%. If it is higher, then free combination between pairs of alleles is observed, indistinguishable from independent inheritance.

The biological significance of crossing over is extremely great, since genetic recombination makes it possible to create new, previously non-existent combinations of genes and thereby increase hereditary variability, which provides ample opportunities for the organism to adapt to various environmental conditions. A person specifically carries out hybridization in order to obtain the necessary combinations for use in breeding work.

Traction and crossing over. From the principles of genetic analysis set out in previous chapters, it clearly follows that independent combination of traits can only be carried out under the condition that the genes that determine these traits are located on non-homologous chromosomes. Consequently, in each organism the number of pairs of characters for which independent inheritance is observed is limited by the number of pairs of chromosomes. On the other hand, it is obvious that the number of characteristics and properties of an organism controlled by genes is extremely large, and the number of pairs of chromosomes in each species is relatively small and constant.

It remains to assume that each chromosome contains not one gene, but many. If this is so, then Mendel's third law concerns the distribution of chromosomes, not genes, i.e. its effect is limited.

The phenomenon of linked inheritance. From Mendel's third law it follows that when crossing forms that differ in two pairs of genes (AB And ab), it turns out to be a hybrid AaBb, forming four types of gametes AB, Ab, aB And ab in equal quantities.

In accordance with this, in analyzing crossing a splitting of 1: 1: 1: 1 is carried out, i.e. combinations of characteristics characteristic of parent forms (AB And ab), occur with the same frequency as new combinations (Ab And aB),- 25% each. However, as evidence accumulated, geneticists increasingly began to encounter deviations from independent inheritance. In some cases, new combinations of features (Ab And aB) V Fb were completely absent - complete linkage was observed between the genes of the original forms. But more often in the offspring, parental combinations of traits predominated to one degree or another, and new combinations occurred with less frequency than expected with independent inheritance, i.e. less than 50%. Thus, in this case, genes were more often inherited in the original combination (they were linked), but sometimes this linkage was broken, giving new combinations.

Morgan proposed to call the joint inheritance of genes, limiting their free combination, the linkage of genes or linked inheritance.

Crossing over and its genetic proof. Assuming that more than one gene is located on one chromosome, the question arises whether the alleles of one gene in a homologous pair of chromosomes can change places, moving from one homologous chromosome to another. If such a process did not occur, then genes would be combined only through the random divergence of non-homologous chromosomes in meiosis, and genes located in one pair of homologous chromosomes would always be inherited linked - as a group.

Research by T. Morgan and his school has shown that genes are regularly exchanged in a homologous pair of chromosomes. The process of exchange of identical sections of homologous chromosomes with the genes they contain is called chromosome crossing or crossing over. Crossing over provides new combinations of genes located on homologous chromosomes. The phenomenon of crossing over, as well as linkage, turned out to be common to all animals, plants and microorganisms. The presence of exchange of identical sections between homologous chromosomes ensures the exchange or recombination of genes and thereby significantly increases the role of combinative variability in evolution. The crossover of chromosomes can be judged by the frequency of occurrence of organisms with a new combination of characteristics. Such organisms are called recombinants.

Gametes with chromosomes that have undergone crossing over are called crossover, and those that have not undergone are called non-crossover. Accordingly, organisms that arose from the combination of crossover gametes of a hybrid with gametes of the analyzer are called crossovers or recombinants, and those that arose due to non-crossover gametes of a hybrid are called non-crossover or non-recombinant.

Morgan's Law of Coupling. When analyzing splitting in the case of crossing over, attention is drawn to a certain quantitative ratio of crossover and non-crossover classes. Both initial parental combinations of traits, formed from non-crossover gametes, appear in the offspring of the analyzing cross in equal quantitative proportions. In the above experiment with Drosophila, there were approximately 41.5% of both individuals. In total, non-crossover flies accounted for 83% of the total number of offspring. The two crossover classes are also identical in number of individuals, and their sum is 17%.

The frequency of crossing over does not depend on the allelic state of the genes involved in the crossing. If flies and are used as a parent, then in the analyzing crossing crossovers ( b + vg And bvg+) and non-crossover ( bvg And b + vg +) individuals will appear with the same frequency (17 and 83%, respectively) as in the first case.

The results of these experiments show that gene linkage really exists, and only in a certain percentage of cases is it disrupted due to crossing over. Hence, it was concluded that mutual exchange of identical regions can take place between homologous chromosomes, as a result of which genes located in these regions of paired chromosomes move from one homologous chromosome to another. The absence of crossover (complete linkage) between genes is an exception and is known only in the heterogametic sex of a few species, for example, Drosophila and silkworm.

The linked inheritance of traits studied by Morgan was called Morgan's law of linkage. Since recombination occurs between genes, and the gene itself is not divided by crossing over, it began to be considered a unit of crossing over.

Crossover amount. The magnitude of crossing over is measured by the ratio of the number of crossover individuals to the total number of individuals in the offspring from the analyzing cross. Recombination occurs reciprocally, i.e. mutual exchange occurs between the parent chromosomes; this forces crossover classes to be counted together as the result of a single event. The crossover value is expressed as a percentage. One percent crossing over equals one unit of distance between genes.

Linear arrangement of genes on a chromosome. T. Morgan suggested that genes are located linearly on chromosomes, and the frequency of crossing over reflects the relative distance between them: the more often crossing over occurs, the farther the genes are from each other on the chromosome; the less often the crossing over, the closer they are to each other.

One of Morgan's classic experiments on Drosophila, proving the linear arrangement of genes, was the following. Females heterozygous for three linked recessive genes that determine yellow body color y, white eye color w and forked wings bi, were crossed with males homozygous for these three genes. In the offspring, 1.2% of crossover flies were obtained, which arose from crossover between genes at And w; 3.5% - from crossing over between genes w And bi and 4.7% - between at And bi.

It is clear from these data that the percentage of crossover is a function of the distance between genes. Since the distance between extreme genes at And bi equal to the sum of two distances between at And w, w And bi, it should be assumed that the genes are located sequentially on the chromosome, i.e. linear.

The reproducibility of these results in repeated experiments indicates that the location of genes in the chromosome is strictly fixed, that is, each gene occupies its own specific place in the chromosome - a locus.

The basic principles of the chromosomal theory of heredity - the pairing of alleles, their reduction in meiosis and the linear arrangement of genes in the chromosome - correspond to the single-stranded chromosome model.

Single and multiple crosses. Having accepted the position that there can be many genes on a chromosome and that they are located on the chromosome in a linear order, and each gene occupies a specific locus in the chromosome, Morgan admitted that crossover between homologous chromosomes can occur simultaneously at several points. This assumption was also proven by him on Drosophila, and then completely confirmed on a number of other animals, as well as on plants and microorganisms.

Crossing over that occurs in only one place is called single, at two points at the same time - double, at three - triple, etc., i.e. it can be multiple.

The further apart the genes are from each other on the chromosome, the greater the likelihood of double crossovers between them. The percentage of recombinations between two genes more accurately reflects the distance between them, the smaller it is, since in the case of a small distance the possibility of double exchanges decreases.

To account for double crossing over, it is necessary to have an additional marker located between the two genes being studied. The distance between genes is determined as follows: the double percentage of double crossover classes is added to the sum of the percentages of single crossover classes. Doubling the percentage of double crossovers is necessary due to the fact that each double crossover occurs due to two independent single breaks at two points.

Interference. It has been established that crossing over that occurs in one place on the chromosome suppresses crossing over in nearby areas. This phenomenon is called interference. In double crossover, interference is especially strong in the case of small distances between genes. Chromosome breaks turn out to be dependent on each other. The degree of this dependence is determined by the distance between the ruptures that occur: as one moves away from the rupture site, the possibility of another rupture increases.

The interference effect is measured by the ratio of the number of observed double discontinuities to the number of possible ones, assuming complete independence of each of the discontinuities.

Gene localization. If genes are located linearly on a chromosome, and the crossover frequency reflects the distance between them, then the location of the gene on the chromosome can be determined.

Before determining the position of a gene, i.e. its localization, it is necessary to determine on which chromosome the gene is located. Genes located on the same chromosome and inherited linked form a linkage group. Obviously, the number of linkage groups in each species must correspond to the haploid set of chromosomes.

To date, linkage groups have been identified in the most genetically studied objects, and in all these cases, complete correspondence of the number of linkage groups to the haploid number of chromosomes has been found. So, in corn ( Zea mays) the haploid set of chromosomes and the number of linkage groups are 10, in peas ( Pisum sativum) - 7, fruit flies (Drosophila melanogaster) - 4, house mice ( Mus musculus) - 20, etc.

Since a gene occupies a specific place in a linkage group, this makes it possible to establish the order of genes on each chromosome and construct genetic maps of chromosomes.

Genetic maps. A genetic map of chromosomes is a diagram of the relative location of genes located in a given linkage group. They have been compiled so far only for some of the most studied objects from a genetic point of view: Drosophila, corn, tomatoes, mice, Neurospora, Escherichia coli, etc.

Genetic maps are compiled for each pair of homologous chromosomes. Clutch groups are numbered.

In order to draw up maps, it is necessary to study the patterns of inheritance of a large number of genes. In Drosophila, for example, more than 500 genes localized in four linkage groups have been studied; in corn, more than 400 genes localized in ten linkage groups, etc. When compiling genetic maps, the linkage group, the full or abbreviated name of the genes, the distance as a percentage from one of the ends of the chromosome, taken as the zero point, are indicated; sometimes the location of the centromere is indicated.

In multicellular organisms, gene recombination is reciprocal. In microorganisms it can be one-sided. Thus, in a number of bacteria, for example, E. coli ( Escherichia coli), the transfer of genetic information occurs during cell conjugation. The only chromosome of a bacterium, which has the shape of a closed ring, always breaks during conjugation at a certain point and passes from one cell to another.

The length of the transferred chromosome region depends on the duration of conjugation. The sequence of genes on a chromosome appears to be constant. Because of this, the distance between genes on such a ring map is measured not in percentage crossing over, but in minutes, which reflects the duration of conjugation.

Cytological evidence of crossing over. After the phenomenon of crossing over had been established using genetic methods, it was necessary to obtain direct evidence of the exchange of sections of homologous chromosomes, accompanied by gene recombination. The patterns of chiasmata observed in the prophase of meiosis can serve only as indirect evidence of this phenomenon; it is impossible to state the exchange that has occurred by direct observation, since the homologous chromosomes exchanging sections are usually absolutely identical in size and shape.

To compare the cytological maps of giant chromosomes with genetic ones, Bridges proposed using the crossing over coefficient. To do this, he divided the total length of all salivary gland chromosomes (1180 μm) by the total length of the genetic maps (279 units). On average, this ratio turned out to be 4.2. Therefore, each unit of crossover on the genetic map corresponds to 4.2 μm on the cytological map (for salivary gland chromosomes). Knowing the distance between genes on the genetic map of a chromosome, you can compare the relative frequency of crossover in its different regions. For example, in X- Drosophila chromosome genes at And ec are at a distance of 5.5%, therefore, the distance between them in the giant chromosome should be 4.2 μm X 5.5 = 23 μm, but direct measurement gives 30 μm. So in this area X-chromosome crossing over occurs less frequently than average.

Due to the uneven implementation of exchanges along the length of chromosomes, genes, when they are plotted on a map, are distributed on it with different densities. Consequently, the distribution of genes on genetic maps can be considered as an indicator of the possibility of crossover along the length of the chromosome.

Crossing over mechanism. Even before the discovery of chromosome crossing by genetic methods, cytologists, studying the prophase of meiosis, observed the phenomenon of mutual entwining of chromosomes, the formation of χ-shaped figures by them - chiasmus (χ is the Greek letter “chi”). In 1909, F. Janssens suggested that chiasmata are associated with the exchange of chromosome sections. Subsequently, these pictures served as an additional argument in favor of the hypothesis of genetic crossover of chromosomes, put forward by T. Morgan in 1911.

The mechanism of chromosome crossing is associated with the behavior of homologous chromosomes in prophase I of meiosis.

Crossing over occurs at the four-chromatid stage and is associated with the formation of chiasmata.

If in one bivalent there was not one exchange, but two or more, then in this case several chiasmata are formed. Since there are four chromatids in the bivalent, then, obviously, each of them has an equal probability of exchanging sections with any other. In this case, two, three or four chromatids can participate in the exchange.

Exchange within sister chromatids cannot lead to recombination, since they are genetically identical, and therefore such exchange does not make sense as a biological mechanism of combinative variation.

Somatic (mitotic) crossing over. As already mentioned, crossing over occurs in prophase I of meiosis during the formation of gametes. However, there is somatic, or mitotic, crossing over, which occurs during the mitotic division of somatic cells, mainly embryonic tissues.

It is known that homologous chromosomes in prophase of mitosis usually do not conjugate and are located independently of each other. However, sometimes it is possible to observe synapsis of homologous chromosomes and figures similar to chiasmata, but no reduction in the number of chromosomes is observed.

Hypotheses about the crossing-over mechanism. There are several hypotheses regarding the mechanism of crossover, but none of them fully explains the facts of gene recombination and the cytological patterns observed during this process.

According to the hypothesis proposed by F. Janssens and developed by K. Darlington, during the synapsis of homologous chromosomes in the bivalent, a dynamic tension is created that arises in connection with the spiralization of chromosome threads, as well as during the mutual entwining of homologs in the bivalent. Due to this tension, one of the four chromatids breaks. The break, disturbing the balance in the bivalent, leads to a compensatory break at a strictly identical point on any other chromatid of the same bivalent. Then a reciprocal reunion of the broken ends occurs, leading to crossing over. According to this hypothesis, chiasmata are directly related to crossing over.

According to K. Sachs's hypothesis, chiasmata are not the result of crossing over: first, chiasmata are formed, and then an exchange occurs. When chromosomes diverge to the poles due to mechanical stress, breaks and exchange of corresponding sections occur in the places of chiasmata. After the exchange, the chiasma disappears.

The meaning of another hypothesis, proposed by D. Belling and modernized by I. Lederberg, is that the process of DNA replication can reciprocally switch from one strand to another; reproduction, having started on one matrix, at some point switches to the DNA matrix strand.

Factors influencing chromosome crossover. Crossing over is influenced by many factors, both genetic and environmental. Therefore, in a real experiment, we can talk about the crossing-over frequency, keeping in mind all the conditions under which it was determined. Crossing over is practically absent between heteromorphs X- And Y-chromosomes. If it were to occur, the chromosomal mechanism for determining sex would be constantly destroyed. The blocking of crossing over between these chromosomes is associated not only with the difference in their size (this is not always observed), but is also due to Y-specific nucleotide sequences. A prerequisite for synapse of chromosomes (or their sections) is homology of nucleotide sequences.

The vast majority of higher eukaryotes are characterized by approximately the same frequency of crossing over in both homogametic and heterogametic sexes. However, there are species in which crossing over is absent in individuals of the heterogametic sex, while in individuals of the homogametic sex it proceeds normally. This situation is observed in heterogametic male Drosophila and female silkworm. It is significant that the frequency of mitotic crossing over in these species is almost the same in males and females, which indicates different elements of control of individual stages of genetic recombination in germ and somatic cells. In heterochromatic regions, particularly pericentromeric regions, the frequency of crossing over is reduced, and therefore the true distance between genes in these regions can be changed.

Genes acting as crossing over inhibitors have been discovered , but there are also genes that increase its frequency. They can sometimes induce a noticeable number of crossovers in male Drosophila. Chromosome rearrangements, in particular inversions, can also act as crossover arresters. They disrupt the normal conjugation of chromosomes in zygotene.

It was found that the frequency of crossing over is influenced by the age of the organism, as well as exogenous factors: temperature, radiation, salt concentration, chemical mutagens, drugs, hormones. With most of these impacts, the frequency of crossing over increases.

In general, crossing over is one of the regular genetic processes controlled by many genes, both directly and through the physiological state of meiotic or mitotic cells. The frequency of various types of recombinations (meiotic, mitotic crossing over and sister, chromatid exchanges) can serve as a measure of the effect of mutagens, carcinogens, antibiotics, etc.

Morgan's laws of inheritance and the principles of heredity arising from them. The works of T. Morgan played a huge role in the creation and development of genetics. He is the author of the chromosomal theory of heredity. They discovered the laws of inheritance: inheritance of sex-linked traits, linked inheritance.

The following principles of heredity follow from these laws:

1. A factor gene is a specific locus of the chromosome.

2. Gene alleles are located in identical loci of homologous chromosomes.

3. Genes are located linearly on the chromosome.

4. Crossing over is a regular process of gene exchange between homologous chromosomes.

Mobile elements of the genome. In 1948, the American researcher McClintock discovered genes in corn that move from one part of the chromosome to another and called the phenomenon transposition, and the genes themselves control elements (CE). 1.These elements can move from one site to another; 2. their integration into a given region affects the activity of genes located nearby; 3. loss of EC in a given locus turns a previously mutable locus into a stable one; 4. in sites where ECs are present, deletions, translocations, transpositions, inversions, and chromosome breaks can occur. In 1983, the Nobel Prize was awarded to Barbara McClintock for the discovery of mobile genetic elements.

The presence of transposable elements in genomes has various consequences:

1. Movements and introduction of transposable elements into genes can cause mutations;

2. Change in the state of gene activity;

3. Formation of chromosomal rearrangements;

4. Telomere formation.

5. Participation in horizontal gene transfer;

6. Transposons based on the P element are used for transformation in eukaryotes, gene cloning, searching for enhancers, etc.

In prokaryotes, there are three types of transposable elements: IS elements (insertions), transposons, and some bacteriophages. IS elements are inserted into any part of DNA, often cause mutations, destroying coding or regulatory sequences, and affect the expression of neighboring genes. A bacteriophage can cause mutations by insertion.

Topic 32. Chromosomal theory of heredity. Morgan's Law

Introduction
1. T. G. Morgan - the greatest geneticist of the 20th century.
2. Attraction and repulsion
3. Chromosomal theory of heredity
4. Mutual arrangement of genes
5. Maps of linkage groups, localization of genes in chromosomes
6. Cytological maps of chromosomes
7. Conclusion
Bibliography

1. INTRODUCTION

Mendel's third law - the rule of independent inheritance of characters - has significant limitations.
In Mendel's own experiments and in the first experiments carried out after the second discovery of Mendel's laws, genes located on different chromosomes were included in the study, and as a result, no discrepancies with Mendel's third law were found. Somewhat later, facts were found that contradict this law. The gradual accumulation and study of them led to the establishment of the fourth law of heredity, called Morgan's law (in honor of the American geneticist Thomas Gent Morgan, who first formulated and substantiated it), or the rule of linkage.
In 1911, in the article “Free segregation as opposed to attraction in Mendelian heredity,” Morgan wrote: “Instead of free segregation in the Mendelian sense, we found an “association of factors” localized close together on the chromosomes. Cytology provided the mechanism required by the experimental data.
These words briefly formulate the main provisions of the chromosomal theory of heredity developed by T. G. Morgan.

1. T. G. MORGAN - THE LARGEST GENETICIST of the 20th century.

Thomas Gent Morgan was born on September 25, 1866 in Kentucky (USA). In 1886 he was graduated from the university of this state. In 1890, T. Morgan received his Doctor of Philosophy degree, and the following year became a professor at a women's college in Pennsylvania. The main period of his life was associated with Columbia University, where from 1904 for 25 years he served as head of the department of experimental zoology. In 1928, he was invited to head a biological laboratory specially built for him at the California Institute of Technology, in a town near Los Angeles, where he worked until his death.
T. Morgan's first studies were devoted to issues of experimental embryology.
In 1902, the young American cytologist Walter Setton (1877-1916), who worked in the laboratory of E. Wilson (1856-1939), suggested that the peculiar phenomena characterizing the behavior of chromosomes during fertilization were, in all likelihood, a mechanism of Mendelian patterns . T. Morgan was well acquainted with E. Wilson himself and with the work of his laboratory, and therefore, when in 1908 he established in male phylloxera the presence of two varieties of sperm, one of which had an additional chromosome, an assumption of a connection immediately arose characteristics of sex with the introduction of appropriate chromosomes. So T. Morgan moved on to the problems of genetics. He came up with the idea that not only gender is associated with chromosomes, but, perhaps, other hereditary inclinations are localized in them.
The modest budget of the university laboratory forced T. Morgan to search for a more suitable object for experiments in the study of heredity. From mice and rats he moves on to the fruit fly Drosophila, the choice of which turned out to be extremely successful. The work of T. Morgan's school, and then most other genetic research institutions, focused on this object. Major discoveries in genetics of the 20-30s. XX century associated with Drosophila.
In 1910, T. Morgan’s first genetic work, “Sex-Limited Heredity in Drosophila,” was published, describing the white-eyed mutation. The subsequent, truly gigantic work of T. Morgan and his colleagues made it possible to link the data of cytology and genetics into a single whole and culminated in the creation of the chromosomal theory of heredity. The major works of T. Morgan “Structural basis of heredity”, “Gene theory”, “Experimental foundations of evolution” and others mark the progressive development of genetic science.
Among biologists of the twentieth century. T. Morgan stands out as a brilliant experimental geneticist and as a researcher of a wide range of issues.
In 1931, T. Morgan was elected an honorary member of the USSR Academy of Sciences, and in 1933 he was awarded the Nobel Prize.

2. ATTRACTION AND REPULSION

For the first time, a deviation from the rule of independent inheritance of characters was noticed by Bateson and Punnett in 1906 when studying the nature of inheritance of flower color and pollen shape in sweet peas. In sweet pea, purple flower color (controlled by the B gene) is dominant over red (depending on gene B), and the oblong shape of mature pollen (“long pollen”), associated with the presence of 3 pores, which is controlled by the L gene, dominates “round” pollen with 2 pores, the formation of which is controlled by the l gene.
When crossing purple sweet peas with long pollen and red sweet peas with round pollen, all first generation plants have purple flowers and long pollen.
In the second generation, among the 6,952 plants studied, 4,831 plants with purple flowers and long pollen, 390 with purple flowers and round pollen, 393 with red flowers and long pollen, and 1,338 with red flowers and round pollen were found.
This ratio corresponds well to the splitting that is expected if, during the formation of gametes of the first generation, genes B and L are found 7 times more often in the combinations in which they were found in the parental forms (BL and bl) than in new combinations (Bl and bL) (Table 1).
It seems that genes B and L, as well as b and l, are attracted to each other and can only be separated from one another with difficulty. This behavior of genes was called gene attraction. The assumption that gametes with the B and L genes in the combinations in which they were presented in the parental forms are found 7 times more often than gametes with a new combination (in this case Bl and bL) was directly confirmed in the results as called analyzing crosses.
When crossing first generation (F1) hybrids (genotype BbLl) with a recessive parent (bbll), the following split was obtained: 50 plants with purple flowers and long pollen, 7 plants with purple flowers and round pollen, 8 plants with red flowers and long pollen, and 47 plants with red flowers and round pollen, which corresponds very well to the expected ratio: 7 gametes with old gene combinations to 1 gamete with new combinations.
In those crosses where one of the parents had the BBll genotype and the other the bbLL genotype, segregation in the second generation had a completely different character. In one of these F2 crosses, there were 226 plants with purple flowers and long pollen, 95 with purple flowers and round pollen, 97 with red flowers and long pollen, and one plant with red flowers and round pollen. In this case, it appears that the B and L genes repel each other. This behavior of hereditary factors was called gene repulsion.
Since the attraction and repulsion of genes was very rare, it was considered some kind of anomaly and a kind of genetic curiosity.
Somewhat later, several more cases of attraction and repulsion were discovered in sweet peas (flower shape and leaf axil color, flower color and flower sail shape, and some other pairs of characters), but this did not change the overall assessment of the phenomenon of attraction and repulsion as an anomaly.
However, the assessment of this phenomenon changed dramatically after in 1910-1911. T. Morgan and his students discovered numerous cases of attraction and repulsion in the fruit fly Drosophila, a very favorable object for genetic research: its cultivation is cheap and can be carried out in laboratory conditions on a very wide scale, its lifespan is short and in one year you can get several dozen generations, controlled crossings are easy to implement; there are only 4 pairs of chromosomes, including a pair of sexual ones that are clearly distinguishable from each other.
Thanks to this, Morgan and his collaborators quickly discovered a large number of mutations in hereditary factors that determine traits that are clearly visible and easy to study, and were able to conduct numerous crosses to study the nature of inheritance of these traits. It turned out that many genes in the Drosophila fly are not inherited independently of each other, but are mutually attracted or repelled, and genes showing such interaction could be divided into several groups, within which all genes showed more or less strongly expressed mutual attraction or repulsion.
Based on an analysis of the results of these studies, T. G. Morgan suggested that attraction occurs between non-allelomorphic genes located on the same chromosome and persists until these genes are separated from each other as a result of chromosome breakage during reduction division , and repulsion occurs in cases where the genes being studied are located on different chromosomes of the same pair of homologous chromosomes
It follows that the attraction and repulsion of genes are different aspects of the same process, the material basis of which is the different arrangement of genes in the chromosomes. Therefore, Morgan proposed to abandon the two separate concepts of “attraction” and “repulsion” of genes and replace it with one general concept of “gene linkage,” believing that it depends on their location within one chromosome in a linear order.

3. CHROMOSOMAL THEORY OF HERITAGE

Upon further study of gene linkage, it was soon established that the number of linkage groups in Drosophila (4 groups) corresponds to the haploid number of chromosomes in this fly, and all genes studied in sufficient detail were distributed among these 4 linkage groups. Initially, the relative location of genes within a chromosome remained unknown, but later a technique was developed to determine the order of location of genes included in the same linkage group, based on the quantitative determination of the strength of linkage between them.
Quantitative determination of gene linkage strength is based on the following theoretical premises. If two genes A and B in a diploid organism are located on one chromosome, and recessive allelomorphs of these genes a and b are located on another chromosome homologous to it, then genes A and B can separate from each other and enter into new combinations with their recessive allelomorphs only in in the event that the chromosome in which they are located is broken in the area between these genes and at the site of the break a connection occurs between sections of this chromosome and its homolog.
Such breaks and new combinations of chromosome regions actually occur during the conjugation of homologous chromosomes during reduction division. But in this case, exchanges of sections usually do not occur between all 4 chromatids that make up the chromosomes of bivalents, but only between two of these 4 chromatids. Therefore, the chromosomes formed as a result of the first division of meiosis, during such exchanges, consist of two unequal chromatids - unchanged and reconstructed as a result of the exchange. In the II division of meiosis, these unequal chromatids diverge to opposite poles, and thanks to this, haploid cells resulting from reduction division (spores or gametes) receive chromosomes consisting of identical chromatids, but only half of the haploid cells receive reconstructed chromosomes, and the second half receive unchanged.
This exchange of chromosome sections is called crossing over. All other things being equal, crossing over between two genes located on the same chromosome occurs less frequently the closer they are located to each other. The frequency of crossing over between genes is proportional to the distance between them.
Determining the frequency of crossing over is usually done using so-called analytical crosses (crossing F1 hybrids with a recessive parent), although F2 obtained from selfing of F1 hybrids or crossing F1 hybrids with each other can also be used for this purpose.
We can consider this determination of the frequency of crossing over using the example of the strength of adhesion between the C and S genes in maize. The C gene determines the formation of colored endosperm (colored seeds), and its recessive allele c causes uncolored endosperm. The S gene causes the formation of smooth endosperm, and its recessive allele s determines the formation of wrinkled endosperm. Genes C and S are located on the same chromosome and are quite strongly linked to each other. In one of the experiments conducted to quantify the strength of adhesion of these genes, the following results were obtained.
A plant with colored smooth seeds, homozygous for the C and S genes and having the CCSS genotype (dominant parent), was crossed with a plant with uncolored wrinkled seeds with the CCSS genotype (recessive parent). First generation F1 hybrids were recrossed to the recessive parent (test cross). In this way, 8368 F2 seeds were obtained, in which the following splitting was found based on color and wrinkles: 4032 colored smooth seeds; 149 painted wrinkled; 152 unpainted smooth; 4035 undyed wrinkled.
If, during the formation of macro- and microspores in F1 hybrids, the C and S genes were distributed independently of each other, then in the testing cross all these four groups of seeds should be represented in equal numbers. But this is not the case, since the C and S genes are located on the same chromosome, linked to each other, and as a result, disputes with recombined chromosomes containing the Cs and cS genes are formed only in the presence of crossing over between the C and S genes, which occurs relatively rare.
The percentage of crossing over between genes C and S can be calculated using the formula:

X = a + b / n x 100%,

Where a is the number of crossing over grains of one class (grains with the Cscs genotype, derived from the combination of gametes Cs of the F1 hybrid with gametes cs of the recessive parent); c is the number of crossing-over grains of the second class (cScs); n is the total number of grains obtained as a result of analyzing crossing.
Diagram showing the inheritance of chromosomes containing linked genes in maize (according to Hutchinson). The hereditary behavior of the genes for colored (C) and colorless (c) aleurone, full (S) and wrinkled (s) endosperm, as well as the chromosomes carrying these genes when crossing two pure types with each other and when backcrossing F1 with a double recessive is indicated.
Substituting the number of grains of different classes obtained in this experiment into the formula, we obtain:

X = a + b / n x 100% = 149 + 152 / 8368 x 100% = 3.6%

The distance between genes in linkage groups is usually expressed as a percentage of crossing over, or in morganids (a morganid is a unit expressing the strength of linkage, named at the suggestion of A. S. Serebrovsky in honor of T. G. Morgan, equal to 1% crossing over). In this case, we can say that the C gene is located at a distance of 3.6 morganids from the S gene.
Now you can use this formula to determine the distance between B and L in sweet peas. Substituting the numbers obtained from analytical crossing and given above into the formula, we get:

X = a + b / n x 100% = 7 + 8 / 112 x 100% = 11.6%

In sweet peas, genes B and L are located on the same chromosome at a distance of 11.6 morganids from each other.
In the same way, T. G. Morgan and his students determined the percentage of crossing over between many genes included in the same linkage group for all four Drosophila linkage groups. It turned out that the percentage of crossing over (or the distance in morganids) between different genes that are part of the same linkage group turned out to be sharply different. Along with genes between which crossing over occurred very rarely (about 0.1%), there were also genes between which linkage was not detected at all, which indicated that some genes are located very close to each other, while others are very close to each other. far.

4. RELATIVE LOCATION OF GENES

To figure out the location of genes, it was assumed that they were arranged in a linear order on chromosomes and that the true distance between two genes was proportional to the frequency of crossing over between them. These assumptions opened up the possibility of determining the relative position of genes within linkage groups.
Suppose the distances (% crossing over) between three genes A, B and C are known and that they are 5% between genes A and B, 3% between B and C and 8% between genes A and C.
Let's assume that gene B is located to the right of gene A. In which direction from gene B should gene C be located?
If we assume that gene C is located to the left of gene B, then in this case the distance between gene A and C should be equal to the difference in the distances between genes A - B and B - C, i.e. 5% - 3% = 2%. But in reality, the distance between genes A and C is completely different and is equal to 8%. Therefore the assumption is incorrect.
If we now assume that gene C is located to the right of gene B, then in this case the distance between genes A and C should be equal to the sum of the distances between genes A - B and genes B - C, i.e. 5% + 3% = 8 %, which fully corresponds to the distance established experimentally. Therefore, this assumption is correct, and the location of genes A, B and C on the chromosome can be schematically depicted as follows: A - 5%, B - 3%, C - 8%.
Once the relative positions of the 3 genes have been established, the location of the fourth gene in relation to these three can be determined by knowing its distance from only 2 of these genes. We can assume that the distance of gene D from two genes - B and C from among the 3 genes A, B and C discussed above is known and that it is equal to 2% between genes C and D and 5% between B and D. An attempt to place gene D on the left from gene C is unsuccessful due to the obvious discrepancy between the difference in distances between genes B - C and C - D (3% - 2% = 1%) to the given distance between genes B and D (5%). And, on the contrary, placing gene D to the right of gene C gives complete correspondence between the sum of the distances between genes B - C and genes C - D (3% + 2% = 5%) to the given distance between genes B and D (5%). Once we have established the location of gene D relative to genes B and C, without additional experiments we can calculate the distance between genes A and D, since it should be equal to the sum of the distances between genes A - B and B - D (5% + 5 % = 10%).
When studying the linkage between genes included in the same linkage group, an experimental check of the distances between them, previously calculated in the same way as was done above for genes A and D, was repeatedly carried out, and in all cases a very good agreement was obtained.
If the location of 4 genes is known, say A, B, C, D, then the fifth gene can be “linked” to them if the distances between gene E and some two of these 4 genes are known, and the distances between gene E and the other two genes quadruples can be calculated as was done for genes A and D in the previous example.

5. MAPS OF LINKAGE GROUPS, LOCALIZATION OF GENES IN CHROMOSOMES

By gradually linking more and more genes to the original three or four linked genes, for which their relative positions had previously been established, maps of linkage groups were compiled.
When compiling clutch group maps, it is important to consider a number of features. A bivalent may experience not one, but two, three, and even more chiasmata and chiasmata-related crossovers. If genes are located very close to each other, then the probability that two chiasmata will arise on the chromosome between such genes and two thread exchanges (two crossovers) will occur is negligible. If genes are located relatively far from each other, the probability of double crossing over in the chromosome region between these genes in the same pair of chromatids increases significantly. Meanwhile, the second crossover in the same pair of chromatids between the genes being studied, in fact, cancels the first crossover and eliminates the exchange of these genes between homologous chromosomes. Therefore, the number of crossover gametes decreases and it appears that these genes are located closer to each other than they actually are.
Scheme of double crossing over in one pair of chromatids between genes A and B and genes B and C. I - moment of crossing over; II - recombined chromatids AcB and aCb.
Moreover, the further the studied genes are located from each other, the more often double crossing over occurs between them and the greater the distortion of the true distance between these genes caused by double crossing over.
If the distance between the genes under study exceeds 50 morganids, then it is generally impossible to detect linkage between them by directly determining the number of crossover gametes. In them, as in genes in homologous chromosomes that are not linked to each other, during analytical crossing only 50% of gametes contain a combination of genes different from those that were present in the first generation hybrids.
Therefore, when compiling maps of linkage groups, the distances between distantly located genes are determined not by directly determining the number of crossover gametes in test crosses involving these genes, but by adding the distances between many closely spaced genes located between them.
This method of compiling maps of linkage groups makes it possible to more accurately determine the distance between relatively distant (no more than 50 morganids) located genes and identify the linkage between them if the distance is more than 50 morganids. In this case, linkage between distantly located genes was established due to the fact that they are linked to intermediately located genes, which, in turn, are linked to each other.
Thus, for genes located at opposite ends of the II and III chromosomes of Drosophila - at a distance of more than 100 morganids from each other, it was possible to establish the fact of their location in the same linkage group by identifying their linkage with intermediate genes and the linkage of these intermediate genes between yourself.
Distances between distantly located genes are determined by adding the distances between many intermediate genes, and only thanks to this they are established relatively accurately.
In organisms whose sex is controlled by sex chromosomes, crossing over occurs only in the homogametic sex and is absent in the heterogametic sex. Thus, in Drosophila, crossing over occurs only in females and is absent (more precisely, it occurs a thousand times less frequently) in males. In this regard, the genes of the males of this fly, located on the same chromosome, show complete linkage regardless of their distance from each other, which makes it easier to identify their location in the same linkage group, but makes it impossible to determine the distance between them.
Drosophila has 4 linkage groups. One of these groups is about 70 morganids long, and the genes included in this linkage group are clearly associated with the inheritance of sex. Therefore, it can be considered certain that the genes included in this linkage group are located on the sex X chromosome (in 1 pair of chromosomes).
The other linkage group is very small, and its length is only 3 morganids. There is no doubt that the genes included in this linkage group are located in microchromosomes (IX pair of chromosomes). But the other two linkage groups have approximately the same size (107.5 morganids and 106.2 morganids) and it is quite difficult to decide which of the pairs of autosomes (II and III pairs of chromosomes) each of these linkage groups corresponds to.
To resolve the issue of the location of linkage groups in large chromosomes, it was necessary to use a cytogenetic study of a number of chromosome rearrangements. In this way, it was possible to establish that a slightly larger linkage group (107.5 morganids) corresponds to the II pair of chromosomes, and a slightly smaller linkage group (106.2 morganids) is located in the III pair of chromosomes.
Thanks to this, it was established which chromosomes correspond to each of the linkage groups in Drosophila. But even after this, it remained unknown how gene linkage groups are located in their corresponding chromosomes. Is, for example, the right end of the first linkage group in Drosophila located near the kinetic constriction of the X chromosome or at the opposite end of this chromosome? The same applies to all other clutch groups.
The question of the extent to which the distances between genes expressed in morganids (in % crossing over) corresponded to the true physical distances between them in chromosomes also remained open.
To find out all this, it was necessary, at least for some genes, to establish not only their relative position in linkage groups, but also their physical position in the corresponding chromosomes.
This turned out to be possible only after, as a result of joint research by geneticist G. Meller and cytologist G. Paynter, it was established that under the influence of X-rays in Drosophila (like all living organisms) there is a transfer (translocation) of sections of one chromosome to another. When a certain section of one chromosome is transferred to another, all genes located in this section lose linkage with genes located in the rest of the donor chromosome and gain linkage with genes in the recipient chromosome. (Later it was found that with such chromosome rearrangements, there is not just a transfer of a section from one chromosome to another, but a mutual transfer of a section of the first chromosome to the second, and from it a section of the second chromosome is transferred to the place of the separated section in the first).
In cases where a chromosome break, when separating a region transferred to another chromosome, occurs between two genes located close to each other, the location of this break can be determined quite accurately both on the linkage group map and on the chromosome. On a linkage map, the breakpoint is located in the area between the extreme genes, of which one remains in the previous linkage group, and the other is included in the new one. On a chromosome, the location of the break is determined by cytological observations of a decrease in the size of the donor chromosome and an increase in the size of the recipient chromosome.
Translocation of sections from chromosome 2 to chromosome 4 (according to Morgan). The upper part of the figure shows the linkage groups, the middle part shows the chromosomes corresponding to these linkage groups, and the bottom shows the metaphase plates of somatic mitosis. The numbers indicate the numbers of linkage groups and chromosomes. A and B - the “lower” part of the chromosome has moved to chromosome 4; B - the “upper” part of chromosome 2 has moved to chromosome 4. Genetic maps and chromosome plates are heterozygous for translocations.
As a result of the study of a large number of different translocations carried out by many geneticists, so-called cytological maps of chromosomes were compiled. The locations of all the studied breaks are marked on the chromosomes, and thanks to this, the location of two neighboring genes to the right and left of it is established for each break.
Cytological maps of chromosomes first of all made it possible to establish which ends of the chromosomes correspond to the “right” and “left” ends of the corresponding linkage groups.
Comparison of “cytological” maps of chromosomes with “genetic” (linkage groups) provides essential material for elucidating the relationship between the distances between neighboring genes expressed in morganids and the physical distances between the same genes in chromosomes when studying these chromosomes under a microscope.
Comparison of “genetic maps” of chromosomes I, II and III of Drosophila melanogaster with “cytological maps” of these chromosomes in metaphase based on translocation data (according to Levitsky). Sp is the site of attachment of the spindle threads. The rest indicate various genes.
Somewhat later, a triple comparison of the location of genes on “genetic maps” of linkage, “cytological maps” of ordinary somatic chromosomes and “cytological maps” of giant salivary glands was performed.
In addition to Drosophila, fairly detailed “genetic maps” of linkage groups have been compiled for some other species of the genus Drosophila. It turned out that in all species studied in sufficient detail, the number of linkage groups is equal to the haploid number of chromosomes. Thus, in Drosophila, which has three pairs of chromosomes, 3 linkage groups were found, in Drosophila with five pairs of chromosomes - 5, and in Drosophila with six pairs of chromosomes - 6 linkage groups.
Among vertebrates, the best studied is the house mouse, in which 18 linkage groups have already been established, while there are 20 pairs of chromosomes. In humans, who have 23 pairs of chromosomes, 10 linkage groups are known. A chicken with 39 pairs of chromosomes has only 8 linkage groups. There is no doubt that with further genetic study of these objects, the number of identified linkage groups in them will increase and, probably, will correspond to the number of pairs of chromosomes.
Among higher plants, corn is the most genetically studied. It has 10 pairs of chromosomes and 10 fairly large linkage groups have been found. With the help of experimentally obtained translocations and some other chromosomal rearrangements, all these linkage groups are confined to strictly defined chromosomes.
In some higher plants, studied in sufficient detail, complete correspondence was also established between the number of linkage groups and the number of pairs of chromosomes. Thus, barley has 7 pairs of chromosomes and 7 linkage groups, tomato has 12 pairs of chromosomes and 12 linkage groups, snapdragon has a haploid chromosome number of 8 and 8 linkage groups have been established.
Among the lower plants, the marsupial fungus has been studied genetically in the most detail. It has a haploid chromosome number of 7 and 7 linkage groups have been established.
It is now generally accepted that the number of linkage groups in all organisms is equal to their haploid number of chromosomes, and if in many animals and plants the number of known linkage groups is less than their haploid number of chromosomes, then this only depends on the fact that they have been genetically studied insufficient and, as a result, only part of the available linkage groups have been identified.

CONCLUSION

As a result, we can quote excerpts from the works of T. Morgan:
"... Since linkage takes place, it appears that the division of the hereditary substance is to some extent limited. For example, about 400 new types of mutants are known in the fruit fly Drosophila, the features of which are only four linkage groups...
... Members of a linkage group may sometimes not be so fully linked to each other, ... some of the recessive characters of one series may be replaced by wild-type characters from another series. However, even in this case, they are still considered linked, because they remain connected together more often than such an exchange between series is observed. This exchange is called CROSS-ING-OVER - crossing over. This term means that between two corresponding series of linkage, a correct exchange of their parts can occur, in which a large number of genes are involved...
The gene theory establishes that the characteristics or properties of an individual are a function of paired elements (genes) embedded in the hereditary substance in the form of a certain number of linkage groups; it then establishes that the members of each pair of genes, when the germ cells mature, are divided in accordance with Mendel's first law and, therefore, each mature germ cell contains only one assortment of them; it also establishes that members belonging to different linkage groups are distributed independently during inheritance, in accordance with Mendel’s second law; in the same way, it establishes that sometimes there is a natural interchange - cross - between the corresponding elements of two linkage groups; finally, it establishes that the frequency of the cross provides data proving the linear arrangement of the elements in relation to each other ... "

BIBLIOGRAPHY

1. General genetics. M.: Higher School, 1985.
2. Reader on genetics. Kazan University Publishing House, 1988.
3. Petrov D. F. Genetics with the basics of selection, M.: Higher school, 1971.
4. Biology. M.: Mir, 1974.

Topic 32. Chromosomal theory of heredity. Morgan's Law

Introduction
1. T. G. Morgan - the greatest geneticist of the 20th century.
2. Attraction and repulsion
3. Chromosomal theory of heredity
4. Mutual arrangement of genes
5. Maps of linkage groups, localization of genes in chromosomes
6. Cytological maps of chromosomes
7. Conclusion
Bibliography

1. INTRODUCTION

Mendel's third law - the rule of independent inheritance of characters - has significant limitations.
In Mendel's own experiments and in the first experiments carried out after the second discovery of Mendel's laws, genes located on different chromosomes were included in the study, and as a result, no discrepancies with Mendel's third law were found. Somewhat later, facts were found that contradict this law. The gradual accumulation and study of them led to the establishment of the fourth law of heredity, called Morgan's law (in honor of the American geneticist Thomas Gent Morgan, who first formulated and substantiated it), or the rule of linkage.
In 1911, in the article “Free segregation as opposed to attraction in Mendelian heredity,” Morgan wrote: “Instead of free segregation in the Mendelian sense, we found an “association of factors” localized close together on the chromosomes. Cytology provided the mechanism required by the experimental data.
These words briefly formulate the main provisions of the chromosomal theory of heredity developed by T. G. Morgan.

1. T. G. MORGAN - THE LARGEST GENETICIST of the 20th century.

Thomas Gent Morgan was born on September 25, 1866 in Kentucky (USA). In 1886 he was graduated from the university of this state. In 1890, T. Morgan received his Doctor of Philosophy degree, and the following year became a professor at a women's college in Pennsylvania. The main period of his life was associated with Columbia University, where from 1904 for 25 years he served as head of the department of experimental zoology. In 1928, he was invited to head a biological laboratory specially built for him at the California Institute of Technology, in a town near Los Angeles, where he worked until his death.
T. Morgan's first studies were devoted to issues of experimental embryology.
In 1902, the young American cytologist Walter Setton (1877-1916), who worked in the laboratory of E. Wilson (1856-1939), suggested that the peculiar phenomena characterizing the behavior of chromosomes during fertilization were, in all likelihood, a mechanism of Mendelian patterns . T. Morgan was well acquainted with E. Wilson himself and with the work of his laboratory, and therefore, when in 1908 he established in male phylloxera the presence of two varieties of sperm, one of which had an additional chromosome, an assumption of a connection immediately arose characteristics of sex with the introduction of appropriate chromosomes. So T. Morgan moved on to the problems of genetics. He came up with the idea that not only gender is associated with chromosomes, but, perhaps, other hereditary inclinations are localized in them.
The modest budget of the university laboratory forced T. Morgan to search for a more suitable object for experiments in the study of heredity. From mice and rats he moves on to the fruit fly Drosophila, the choice of which turned out to be extremely successful. The work of T. Morgan's school, and then most other genetic research institutions, focused on this object. Major discoveries in genetics of the 20-30s. XX century associated with Drosophila.
In 1910, T. Morgan’s first genetic work, “Sex-Limited Heredity in Drosophila,” was published, describing the white-eyed mutation. The subsequent, truly gigantic work of T. Morgan and his colleagues made it possible to link the data of cytology and genetics into a single whole and culminated in the creation of the chromosomal theory of heredity. The major works of T. Morgan “Structural basis of heredity”, “Gene theory”, “Experimental foundations of evolution” and others mark the progressive development of genetic science.
Among biologists of the twentieth century. T. Morgan stands out as a brilliant experimental geneticist and as a researcher of a wide range of issues.
In 1931, T. Morgan was elected an honorary member of the USSR Academy of Sciences, and in 1933 he was awarded the Nobel Prize.

2. ATTRACTION AND REPULSION

For the first time, a deviation from the rule of independent inheritance of characters was noticed by Bateson and Punnett in 1906 when studying the nature of inheritance of flower color and pollen shape in sweet peas. In sweet pea, purple flower color (controlled by the B gene) is dominant over red (depending on gene B), and the oblong shape of mature pollen (“long pollen”), associated with the presence of 3 pores, which is controlled by the L gene, dominates “round” pollen with 2 pores, the formation of which is controlled by the l gene.
When crossing purple sweet peas with long pollen and red sweet peas with round pollen, all first generation plants have purple flowers and long pollen.
In the second generation, among the 6,952 plants studied, 4,831 plants with purple flowers and long pollen, 390 with purple flowers and round pollen, 393 with red flowers and long pollen, and 1,338 with red flowers and round pollen were found.
This ratio corresponds well to the splitting that is expected if, during the formation of gametes of the first generation, genes B and L are found 7 times more often in the combinations in which they were found in the parental forms (BL and bl) than in new combinations (Bl and bL) (Table 1).
It seems that genes B and L, as well as b and l, are attracted to each other and can only be separated from one another with difficulty. This behavior of genes was called gene attraction. The assumption that gametes with the B and L genes in the combinations in which they were presented in the parental forms are found 7 times more often than gametes with a new combination (in this case Bl and bL) was directly confirmed in the results as called analyzing crosses.
When crossing first generation (F1) hybrids (genotype BbLl) with a recessive parent (bbll), the following split was obtained: 50 plants with purple flowers and long pollen, 7 plants with purple flowers and round pollen, 8 plants with red flowers and long pollen, and 47 plants with red flowers and round pollen, which corresponds very well to the expected ratio: 7 gametes with old gene combinations to 1 gamete with new combinations.
In those crosses where one of the parents had the BBll genotype and the other the bbLL genotype, segregation in the second generation had a completely different character. In one of these F2 crosses, there were 226 plants with purple flowers and long pollen, 95 with purple flowers and round pollen, 97 with red flowers and long pollen, and one plant with red flowers and round pollen. In this case, it appears that the B and L genes repel each other. This behavior of hereditary factors was called gene repulsion.
Since the attraction and repulsion of genes was very rare, it was considered some kind of anomaly and a kind of genetic curiosity.
Somewhat later, several more cases of attraction and repulsion were discovered in sweet peas (flower shape and leaf axil color, flower color and flower sail shape, and some other pairs of characters), but this did not change the overall assessment of the phenomenon of attraction and repulsion as an anomaly.
However, the assessment of this phenomenon changed dramatically after in 1910-1911. T. Morgan and his students discovered numerous cases of attraction and repulsion in the fruit fly Drosophila, a very favorable object for genetic research: its cultivation is cheap and can be carried out in laboratory conditions on a very wide scale, its lifespan is short and in one year you can get several dozen generations, controlled crossings are easy to implement; there are only 4 pairs of chromosomes, including a pair of sexual ones that are clearly distinguishable from each other.
Thanks to this, Morgan and his collaborators quickly discovered a large number of mutations in hereditary factors that determine traits that are clearly visible and easy to study, and were able to conduct numerous crosses to study the nature of inheritance of these traits. It turned out that many genes in the Drosophila fly are not inherited independently of each other, but are mutually attracted or repelled, and genes showing such interaction could be divided into several groups, within which all genes showed more or less strongly expressed mutual attraction or repulsion.
Based on an analysis of the results of these studies, T. G. Morgan suggested that attraction occurs between non-allelomorphic genes located on the same chromosome and persists until these genes are separated from each other as a result of chromosome breakage during reduction division , and repulsion occurs in cases where the genes being studied are located on different chromosomes of the same pair of homologous chromosomes
It follows that the attraction and repulsion of genes are different aspects of the same process, the material basis of which is the different arrangement of genes in the chromosomes. Therefore, Morgan proposed to abandon the two separate concepts of “attraction” and “repulsion” of genes and replace it with one general concept of “gene linkage,” believing that it depends on their location within one chromosome in a linear order.

3. CHROMOSOMAL THEORY OF HERITAGE

Upon further study of gene linkage, it was soon established that the number of linkage groups in Drosophila (4 groups) corresponds to the haploid number of chromosomes in this fly, and all genes studied in sufficient detail were distributed among these 4 linkage groups. Initially, the relative location of genes within a chromosome remained unknown, but later a technique was developed to determine the order of location of genes included in the same linkage group, based on the quantitative determination of the strength of linkage between them.
Quantitative determination of gene linkage strength is based on the following theoretical premises. If two genes A and B in a diploid organism are located on one chromosome, and recessive allelomorphs of these genes a and b are located on another chromosome homologous to it, then genes A and B can separate from each other and enter into new combinations with their recessive allelomorphs only in in the event that the chromosome in which they are located is broken in the area between these genes and at the site of the break a connection occurs between sections of this chromosome and its homolog.
Such breaks and new combinations of chromosome regions actually occur during the conjugation of homologous chromosomes during reduction division. But in this case, exchanges of sections usually do not occur between all 4 chromatids that make up the chromosomes of bivalents, but only between two of these 4 chromatids. Therefore, the chromosomes formed as a result of the first division of meiosis, during such exchanges, consist of two unequal chromatids - unchanged and reconstructed as a result of the exchange. In the II division of meiosis, these unequal chromatids diverge to opposite poles, and thanks to this, haploid cells resulting from reduction division (spores or gametes) receive chromosomes consisting of identical chromatids, but only half of the haploid cells receive reconstructed chromosomes, and the second half receive unchanged.
This exchange of chromosome sections is called crossing over. All other things being equal, crossing over between two genes located on the same chromosome occurs less frequently the closer they are located to each other. The frequency of crossing over between genes is proportional to the distance between them.
Determining the frequency of crossing over is usually done using so-called analytical crosses (crossing F1 hybrids with a recessive parent), although F2 obtained from selfing of F1 hybrids or crossing F1 hybrids with each other can also be used for this purpose.
We can consider this determination of the frequency of crossing over using the example of the strength of adhesion between the C and S genes in maize. The C gene determines the formation of colored endosperm (colored seeds), and its recessive allele c causes uncolored endosperm. The S gene causes the formation of smooth endosperm, and its recessive allele s determines the formation of wrinkled endosperm. Genes C and S are located on the same chromosome and are quite strongly linked to each other. In one of the experiments conducted to quantify the strength of adhesion of these genes, the following results were obtained.
A plant with colored smooth seeds, homozygous for the C and S genes and having the CCSS genotype (dominant parent), was crossed with a plant with uncolored wrinkled seeds with the CCSS genotype (recessive parent). First generation F1 hybrids were recrossed to the recessive parent (test cross). In this way, 8368 F2 seeds were obtained, in which the following splitting was found based on color and wrinkles: 4032 colored smooth seeds; 149 painted wrinkled; 152 unpainted smooth; 4035 undyed wrinkled.
If, during the formation of macro- and microspores in F1 hybrids, the C and S genes were distributed independently of each other, then in the testing cross all these four groups of seeds should be represented in equal numbers. But this is not the case, since the C and S genes are located on the same chromosome, linked to each other, and as a result, disputes with recombined chromosomes containing the Cs and cS genes are formed only in the presence of crossing over between the C and S genes, which occurs relatively rare.
The percentage of crossing over between genes C and S can be calculated using the formula:

X = a + b / n x 100%,

Where a is the number of crossing over grains of one class (grains with the Cscs genotype, derived from the combination of gametes Cs of the F1 hybrid with gametes cs of the recessive parent); c is the number of crossing-over grains of the second class (cScs); n is the total number of grains obtained as a result of analyzing crossing.
Diagram showing the inheritance of chromosomes containing linked genes in maize (according to Hutchinson). The hereditary behavior of the genes for colored (C) and colorless (c) aleurone, full (S) and wrinkled (s) endosperm, as well as the chromosomes carrying these genes when crossing two pure types with each other and when backcrossing F1 with a double recessive is indicated.
Substituting the number of grains of different classes obtained in this experiment into the formula, we obtain:

X = a + b / n x 100% = 149 + 152 / 8368 x 100% = 3.6%

The distance between genes in linkage groups is usually expressed as a percentage of crossing over, or in morganids (a morganid is a unit expressing the strength of linkage, named at the suggestion of A. S. Serebrovsky in honor of T. G. Morgan, equal to 1% crossing over). In this case, we can say that the C gene is located at a distance of 3.6 morganids from the S gene.
Now you can use this formula to determine the distance between B and L in sweet peas. Substituting the numbers obtained from analytical crossing and given above into the formula, we get:

X = a + b / n x 100% = 7 + 8 / 112 x 100% = 11.6%

In sweet peas, genes B and L are located on the same chromosome at a distance of 11.6 morganids from each other.
In the same way, T. G. Morgan and his students determined the percentage of crossing over between many genes included in the same linkage group for all four Drosophila linkage groups. It turned out that the percentage of crossing over (or the distance in morganids) between different genes that are part of the same linkage group turned out to be sharply different. Along with genes between which crossing over occurred very rarely (about 0.1%), there were also genes between which linkage was not detected at all, which indicated that some genes are located very close to each other, while others are very close to each other. far.

4. RELATIVE LOCATION OF GENES

To figure out the location of genes, it was assumed that they were arranged in a linear order on chromosomes and that the true distance between two genes was proportional to the frequency of crossing over between them. These assumptions opened up the possibility of determining the relative position of genes within linkage groups.
Suppose the distances (% crossing over) between three genes A, B and C are known and that they are 5% between genes A and B, 3% between B and C and 8% between genes A and C.
Let's assume that gene B is located to the right of gene A. In which direction from gene B should gene C be located?
If we assume that gene C is located to the left of gene B, then in this case the distance between gene A and C should be equal to the difference in the distances between genes A - B and B - C, i.e. 5% - 3% = 2%. But in reality, the distance between genes A and C is completely different and is equal to 8%. Therefore the assumption is incorrect.
If we now assume that gene C is located to the right of gene B, then in this case the distance between genes A and C should be equal to the sum of the distances between genes A - B and genes B - C, i.e. 5% + 3% = 8 %, which fully corresponds to the distance established experimentally. Therefore, this assumption is correct, and the location of genes A, B and C on the chromosome can be schematically depicted as follows: A - 5%, B - 3%, C - 8%.
Once the relative positions of the 3 genes have been established, the location of the fourth gene in relation to these three can be determined by knowing its distance from only 2 of these genes. We can assume that the distance of gene D from two genes - B and C from among the 3 genes A, B and C discussed above is known and that it is equal to 2% between genes C and D and 5% between B and D. An attempt to place gene D on the left from gene C is unsuccessful due to the obvious discrepancy between the difference in distances between genes B - C and C - D (3% - 2% = 1%) to the given distance between genes B and D (5%). And, on the contrary, placing gene D to the right of gene C gives complete correspondence between the sum of the distances between genes B - C and genes C - D (3% + 2% = 5%) to the given distance between genes B and D (5%). Once we have established the location of gene D relative to genes B and C, without additional experiments we can calculate the distance between genes A and D, since it should be equal to the sum of the distances between genes A - B and B - D (5% + 5 % = 10%).
When studying the linkage between genes included in the same linkage group, an experimental check of the distances between them, previously calculated in the same way as was done above for genes A and D, was repeatedly carried out, and in all cases a very good agreement was obtained.
If the location of 4 genes is known, say A, B, C, D, then the fifth gene can be “linked” to them if the distances between gene E and some two of these 4 genes are known, and the distances between gene E and the other two genes quadruples can be calculated as was done for genes A and D in the previous example.

5. MAPS OF LINKAGE GROUPS, LOCALIZATION OF GENES IN CHROMOSOMES

By gradually linking more and more genes to the original three or four linked genes, for which their relative positions had previously been established, maps of linkage groups were compiled.
When compiling clutch group maps, it is important to consider a number of features. A bivalent may experience not one, but two, three, and even more chiasmata and chiasmata-related crossovers. If genes are located very close to each other, then the probability that two chiasmata will arise on the chromosome between such genes and two thread exchanges (two crossovers) will occur is negligible. If genes are located relatively far from each other, the probability of double crossing over in the chromosome region between these genes in the same pair of chromatids increases significantly. Meanwhile, the second crossover in the same pair of chromatids between the genes being studied, in fact, cancels the first crossover and eliminates the exchange of these genes between homologous chromosomes. Therefore, the number of crossover gametes decreases and it appears that these genes are located closer to each other than they actually are.

Scheme of double crossing over in one pair of chromatids between genes A and B and genes B and C. I - moment of crossing over; II - recombined chromatids AcB and aCb.
Moreover, the further the studied genes are located from each other, the more often double crossing over occurs between them and the greater the distortion of the true distance between these genes caused by double crossing over.
If the distance between the genes under study exceeds 50 morganids, then it is generally impossible to detect linkage between them by directly determining the number of crossover gametes. In them, as in genes in homologous chromosomes that are not linked to each other, during analytical crossing only 50% of gametes contain a combination of genes different from those that were present in the first generation hybrids.
Therefore, when compiling maps of linkage groups, the distances between distantly located genes are determined not by directly determining the number of crossover gametes in test crosses involving these genes, but by adding the distances between many closely spaced genes located between them.
This method of compiling maps of linkage groups makes it possible to more accurately determine the distance between relatively distant (no more than 50 morganids) located genes and identify the linkage between them if the distance is more than 50 morganids. In this case, linkage between distantly located genes was established due to the fact that they are linked to intermediately located genes, which, in turn, are linked to each other.
Thus, for genes located at opposite ends of the II and III chromosomes of Drosophila - at a distance of more than 100 morganids from each other, it was possible to establish the fact of their location in the same linkage group by identifying their linkage with intermediate genes and the linkage of these intermediate genes between yourself.
Distances between distantly located genes are determined by adding the distances between many intermediate genes, and only thanks to this they are established relatively accurately.
In organisms whose sex is controlled by sex chromosomes, crossing over occurs only in the homogametic sex and is absent in the heterogametic sex. Thus, in Drosophila, crossing over occurs only in females and is absent (more precisely, it occurs a thousand times less frequently) in males. In this regard, the genes of the males of this fly, located on the same chromosome, show complete linkage regardless of their distance from each other, which makes it easier to identify their location in the same linkage group, but makes it impossible to determine the distance between them.
Drosophila has 4 linkage groups. One of these groups is about 70 morganids long, and the genes included in this linkage group are clearly associated with the inheritance of sex. Therefore, it can be considered certain that the genes included in this linkage group are located on the sex X chromosome (in 1 pair of chromosomes).
The other linkage group is very small, and its length is only 3 morganids. There is no doubt that the genes included in this linkage group are located in microchromosomes (IX pair of chromosomes). But the other two linkage groups have approximately the same size (107.5 morganids and 106.2 morganids) and it is quite difficult to decide which of the pairs of autosomes (II and III pairs of chromosomes) each of these linkage groups corresponds to.
To resolve the issue of the location of linkage groups in large chromosomes, it was necessary to use a cytogenetic study of a number of chromosome rearrangements. In this way, it was possible to establish that a slightly larger linkage group (107.5 morganids) corresponds to the II pair of chromosomes, and a slightly smaller linkage group (106.2 morganids) is located in the III pair of chromosomes.
Thanks to this, it was established which chromosomes correspond to each of the linkage groups in Drosophila. But even after this, it remained unknown how gene linkage groups are located in their corresponding chromosomes. Is, for example, the right end of the first linkage group in Drosophila located near the kinetic constriction of the X chromosome or at the opposite end of this chromosome? The same applies to all other clutch groups.
The question of the extent to which the distances between genes expressed in morganids (in % crossing over) corresponded to the true physical distances between them in chromosomes also remained open.
To find out all this, it was necessary, at least for some genes, to establish not only their relative position in linkage groups, but also their physical position in the corresponding chromosomes.
This turned out to be possible only after, as a result of joint research by geneticist G. Meller and cytologist G. Paynter, it was established that under the influence of X-rays in Drosophila (like all living organisms) there is a transfer (translocation) of sections of one chromosome to another. When a certain section of one chromosome is transferred to another, all genes located in this section lose linkage with genes located in the rest of the donor chromosome and gain linkage with genes in the recipient chromosome. (Later it was found that with such chromosome rearrangements, there is not just a transfer of a section from one chromosome to another, but a mutual transfer of a section of the first chromosome to the second, and from it a section of the second chromosome is transferred to the place of the separated section in the first).
In cases where a chromosome break, when separating a region transferred to another chromosome, occurs between two genes located close to each other, the location of this break can be determined quite accurately both on the linkage group map and on the chromosome. On a linkage map, the breakpoint is located in the area between the extreme genes, of which one remains in the previous linkage group, and the other is included in the new one. On a chromosome, the location of the break is determined by cytological observations of a decrease in the size of the donor chromosome and an increase in the size of the recipient chromosome.
Translocation of sections from chromosome 2 to chromosome 4 (according to Morgan). The upper part of the figure shows the linkage groups, the middle part shows the chromosomes corresponding to these linkage groups, and the bottom shows the metaphase plates of somatic mitosis. The numbers indicate the numbers of linkage groups and chromosomes. A and B - the “lower” part of the chromosome has moved to chromosome 4; B - the “upper” part of chromosome 2 has moved to chromosome 4. Genetic maps and chromosome plates are heterozygous for translocations.
As a result of the study of a large number of different translocations carried out by many geneticists, so-called cytological maps of chromosomes were compiled. The locations of all the studied breaks are marked on the chromosomes, and thanks to this, the location of two neighboring genes to the right and left of it is established for each break.
Cytological maps of chromosomes first of all made it possible to establish which ends of the chromosomes correspond to the “right” and “left” ends of the corresponding linkage groups.
Comparison of “cytological” maps of chromosomes with “genetic” (linkage groups) provides essential material for elucidating the relationship between the distances between neighboring genes expressed in morganids and the physical distances between the same genes in chromosomes when studying these chromosomes under a microscope.
Comparison of “genetic maps” of chromosomes I, II and III of Drosophila melanogaster with “cytological maps” of these chromosomes in metaphase based on translocation data (according to Levitsky). Sp is the site of attachment of the spindle threads. The rest indicate various genes.
Somewhat later, a triple comparison of the location of genes on “genetic maps” of linkage, “cytological maps” of ordinary somatic chromosomes and “cytological maps” of giant salivary glands was performed.
In addition to Drosophila, fairly detailed “genetic maps” of linkage groups have been compiled for some other species of the genus Drosophila. It turned out that in all species studied in sufficient detail, the number of linkage groups is equal to the haploid number of chromosomes. Thus, in Drosophila, which has three pairs of chromosomes, 3 linkage groups were found, in Drosophila with five pairs of chromosomes - 5, and in Drosophila with six pairs of chromosomes - 6 linkage groups.
Among vertebrates, the best studied is the house mouse, in which 18 linkage groups have already been established, while there are 20 pairs of chromosomes. In humans, who have 23 pairs of chromosomes, 10 linkage groups are known. A chicken with 39 pairs of chromosomes has only 8 linkage groups. There is no doubt that with further genetic study of these objects, the number of identified linkage groups in them will increase and, probably, will correspond to the number of pairs of chromosomes.
Among higher plants, corn is the most genetically studied. It has 10 pairs of chromosomes and 10 fairly large linkage groups have been found. With the help of experimentally obtained translocations and some other chromosomal rearrangements, all these linkage groups are confined to strictly defined chromosomes.
In some higher plants, studied in sufficient detail, complete correspondence was also established between the number of linkage groups and the number of pairs of chromosomes. Thus, barley has 7 pairs of chromosomes and 7 linkage groups, tomato has 12 pairs of chromosomes and 12 linkage groups, snapdragon has a haploid chromosome number of 8 and 8 linkage groups have been established.
Among the lower plants, the marsupial fungus has been studied genetically in the most detail. It has a haploid chromosome number of 7 and 7 linkage groups have been established.
It is now generally accepted that the number of linkage groups in all organisms is equal to their haploid number of chromosomes, and if in many animals and plants the number of known linkage groups is less than their haploid number of chromosomes, then this only depends on the fact that they have been genetically studied insufficient and, as a result, only part of the available linkage groups have been identified.

CONCLUSION

As a result, we can quote excerpts from the works of T. Morgan:
"...Since linkage takes place, it appears that the division of the hereditary substance is to some extent limited. For example, about 400 new types of mutants are known in the Drosophila fruit fly, the features of which are only four linkage groups...
...Members of a linkage group may sometimes not be so fully linked to each other, ...some of the recessive characters of one series may be replaced by wild-type characters from another series. However, even in this case, they are still considered linked, because they remain connected together more often than such an exchange between series is observed. This exchange is called CROSS-ING-OVER - crossing over. This term means that between two corresponding series of linkage, a correct exchange of their parts can occur, in which a large number of genes are involved...
The gene theory establishes that the characteristics or properties of an individual are a function of paired elements (genes) embedded in the hereditary substance in the form of a certain number of linkage groups; it then establishes that the members of each pair of genes, when the germ cells mature, are divided in accordance with Mendel's first law and, therefore, each mature germ cell contains only one assortment of them; it also establishes that members belonging to different linkage groups are distributed independently during inheritance, in accordance with Mendel’s second law; in the same way, it establishes that sometimes there is a natural interchange - cross - between the corresponding elements of two linkage groups; finally, it establishes that the frequency of the cross provides data proving the linear arrangement of the elements in relation to each other ... "

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