What a taoke chromosome. Human chromosomes. The number of chromosomes in some plants

Jacques Monod's aphorism: "What is true for E. coli is true for other bacteria (elephant)" has become widespread. Fortunately, the reality is not so boring. Until recently, the concept of the circular structure of bacterial chromosomes was generally accepted. However, in 1989, a linear bacterial chromosome was first described in the spirochete Borrelia burgdorfery, which was identified by electrophoresis in a pulsed electric field. The size of this genome was only 960 kbp. It was soon discovered that linear and circular chromosomes coexist simultaneously in Agrobacterium tumefaciens, and Gram-positive bacteria of the genus Streptomyces, which have one of the largest bacterial genomes (~ 8000 kb), have one linear chromosome. The representative of actinomycetes Rhodococcusfascians also appears to have a linear chromosome. Linear chromosomes in bacteria often coexist with linear plasmids and are widespread in nature.

Linear chromosomes and plasmids of the best studied bacteria of the genus Streptomyces contain terminal inverted repeats (TIRs), to which terminal proteins (TP) are covalently linked. Despite the fact that similar structures are typical for the chromosomes of adenoviruses and bacteriophage f29 Bacillus subtilis, the mechanism of chromosome replication of streptomycetes differs significantly from that of viral genomes. If in viruses DNA synthesis is initiated at the end of the chromosome using TP covalently bound to the nucleotide as a primer and continues through the entire genome to its end, then the replication of the chromosome and linear plasmids of streptomycetes begins from the inner region of the origin of replication oriC... DNA synthesis spreads in both directions from the region of the origin of replication by the standard semi-conservative mechanism and ends at the ends of linear DNA molecules with the formation of 3'-terminal gaps (Fig. I.50, a). The simplest solution to the problem of filling this gap could be the direct initiation of replication of telomeric regions of chromosomes from the TP protein covalently linked to the initiating nucleotide, which occurs in adenoviruses (see Fig. I.50, b). Indeed, streptomycetes use TP to replicate telomeric regions; however, the mechanism of telomere recognition in this case is significantly different. Currently, three models of filling gaps in the telomeric regions of linear chromosomes of bacteria are being considered.

Rice. I.50. Model of extension of telomeric regions of chromosomes and plasmids of Streptomyces

a- telomere structure after replication: the upper DNA strand is fully replicated, in the lower one there is a single-stranded gap, four palindromic nucleotide sequences are indicated; b- an unlikely mechanism involving a terminal protein and DNA polymerase; c – d- alternative replication models based on other mechanisms. 1 - terminal protein, 2 - DNA polymerase, 3 - palindrome, 4 - parental DNA strand, 5 - child chain, 6 - reparative synthesis

According to the first model, a single-stranded telomere region containing a TIR sequence forms a terminal hairpin by complementary interactions of nucleotides in the inner regions of the gap and 3'-terminal nucleotides (see Fig. I.50, v). In this case, DNA synthesis, repairing a single-stranded gap, is initiated at a double-stranded region formed by palindromic sequences I-IV, with the participation of TP and DNA polymerase, and continues along the 3'-terminal single-stranded region of the chromosome. According to the second model, TP initiates replication on the fully double-stranded daughter DNA, displacing the 5'-terminal strand of the parental DNA to which TP is linked (see Fig. I.50, G). The displaced strand is then paired with the protruding 3 'end of the chromosome, after which this branched structure is resolved by homologous recombination. This model assumes participation in gap filling of RecA protein (for DNA strand transfer) and gene products ruv(to resolve the structure of Holiday), which is confirmed by genetic data. In the third model, the single-stranded palindrome I forms a hairpin, the 3'-end of which serves as a primer for DNA synthesis, as a result of which the gap is filled (see Fig. I.50, d). TP forms a single-stranded break opposite the original 3 'end, which is the seed for subsequent DNA synthesis. As a result, the hairpin unfolds and the telomere structure is restored. This model is similar to the rolling hairpin model proposed to explain the replication mechanism of the parvovirus genome. In this model, the role of TP differs from its functions as a primer protein in the examples discussed above.

It is not known how many forms of linear bacterial chromosomes exist in nature. Taxonomic problems associated with the topology of chromosomes in the kingdom of eubacteria have not been studied either. If each type of chromosome is characteristic of a separate taxonomic domain, then it can be assumed that the topology of chromosomes plays an important role in the evolution of bacteria. Alternatively, topological interconversions of chromosomes can be relatively frequent events, and linear and ring chromosomes are present only in closely related bacterial species. The instability of streptomycete chromosomes (the formation of extended deletions and amplification of nucleotide sequences) has recently been associated with rearrangements in their terminal regions, some of which were accompanied by the formation of circular chromosomes. Thus, the evolutionary role of the topology of bacterial chromosomes can only be determined as a result of future research.

Eukaryotic replicators

Chromosomes of eukaryotes contain linear DNA molecules, and therefore, the same problems associated with their replication remain, which were discussed in connection with the reproduction of linear chromosomes in bacteria. However, the problems that eukaryotic cells need to solve during the reduplication of their chromosomes are undoubtedly more serious, since the size of the DNA contained in them significantly exceeds the size of the chromosomal DNA of bacterial cells. In addition, due to the multicellularity of most eukaryotes, there is a need for finer coordination of DNA replication in individual fully differentiated and differentiating cells, which is one of the main goals of cell cycle regulation in these organisms. In this regard, the organization of DNA replication in eukaryotes is characterized by a number of essential features.

Rice. I.51. The structure of replicators of the yeast S. cerevisiae

The mutual arrangement of various regulatory elements in replicators is indicated ARS1, ARS307 and ARS305... ACS - canonical sequence ARS, DUE - DNA unwinding element. Subscripts indicate that regulatory elements belong to the corresponding replicators.

The initiation of replication in eukaryotes occurs on specific multiple nucleotide sequences - replicators. The most studied are the replicators of the yeast S . cerevisiae, first identified as autonomously replicating sequences ( ARS- autonomously replicating sequence), capable of supporting extrachromosomal replication of plasmids in yeast cells. Study of the structure ARS1 showed that this chromosomal element consists of several short regulatory sequences. A similar organization is typical for others. ARS yeast (Figure I.51). In particular, ARS307 in addition to the canonical sequence ACS common to all ARS contain two more elements, B1 and B2, which are necessary for the replicator to perform its functions in vivo. Despite the fact that these sequences are not strictly conserved in different replicators, they are functionally interchangeable within groups (B1, B2, etc.). Change of position in relation to ACS prevents their functioning.

The first stage in the initiation of replication in yeast is the interaction of the replicator regulatory sequences with at least six different proteins, which form a complex that recognizes the origin-recognition complex (ORC). ARS determines the place of initiation of replication in yeast cells. Element B3 ARS1 interacts with the Abf1 protein, which stimulates replication with a domain characteristic of transcription activator proteins, while B1 interacts with ORC. The remaining regulatory sequences of the yeast origin of replication form a previously unknown element called DNA unwinding element DUE(DNA-unwinding element) believed to facilitate the unwinding of DNA strands upon initiation of replication. Point mutations in the B2 element do not affect the functions of the replicator, which is a common property of structural elements, while mutations in ACS, B1 and B3 disrupt the initiation of replication, as would be expected from the regulatory elements of nucleic acids interacting with proteins.

Studies of replicators in the yeast S. pombe have shown that the origin of replication ura4 includes three separate replicators, which are located on a DNA site with a length of 5 kb. In mammals, the regions of the origin of replication are located at a distance of ~ 100 kb. from each other; some of them have already been cloned and studied at the molecular level. It was found that DNA synthesis in individual replicons occurs in two directions, and the movement of the replication fork is carried out preferably in one direction, which can vary depending on the stage of development of the organism and the level of expression of genes containing replicators. The frequency of use of individual replicators changes during ontogeny, decreasing in the cells of an adult organism. Comparison of the primary structures of six separate eukaryotic replicators showed that they all contain DUE-elements, sites of attachment to the nuclear matrix (SAR / MAR), canonical ARS- yeast sequences, pyrimidine tracts, as well as previously unidentified canonical sequence WAWTTDDWWWDHWGWHMAWTT, where W = A / T, D = A / C / T, H = A / C / T, and M = A / C. There are some reports that animal replicators contain purine tracts, canonical sequences interacting with transcription factors and proteins of the replicative complex, an enhancer octamer motif, binding sites for oncogen products, AT-rich sequences, and DNA bent sites. At present, it is not completely clear what direct relation all these regulatory sequences have to the initiation of DNA replication. It is assumed that many of them are involved in the regulation of transcription (and, consequently, the regulation of gene expression) as such, since most of the currently known replicators are located in the 5'-terminal sequences of functioning genes.

CHROMOSOMES(Greek chroma color, color + soma body) - the main structural and functional elements of the cell nucleus, containing genes arranged in a linear order and providing storage, reproduction of genetic information, as well as the initial stages of its implementation in signs; change their linear structure in the cell cycle. The term "chromosomes" was proposed by W. Waldeyer in 1888 because of the rod-shaped form and intense staining of these elements with basic dyes during cell division.

The term "chromosome" in its full meaning is applicable to the corresponding nuclear structures of cells of multicellular eukaryotic organisms (see). In the nucleus of such cells, there are always several chromosomes, they make up a chromosome set (see). In somatic cells, chromosomes are paired, since they come from two parental (diploid set of chromosomes), mature germ cells contain a single (haploid) set of chromosomes. Each biological species is characterized by a constant number, size and other morphological characteristics of chromosomes (see Karyotype). In heterosexual organisms, the chromosome set includes two chromosomes carrying genes that determine the sex of an individual (see Gene, Gender), which are called sexual, or gonosomes, as opposed to all the others, called autosomes. In humans, a pair of sex chromosomes is composed: in women, from two X chromosomes (XX set), and in men from X and Y chromosomes (XY set). Therefore, in mature germ cells - gametes, women contain only the X chromosome, while in men half of the spermatozoa contains the X chromosome, and the other contains the Y chromosome.

History

The first observations of chromosomes in the cell nucleus, carried out in the 70s of the 19th century by ID Chistyakov, O. Hertwig, E. Strasburger, laid the foundation for the cytological direction in the study of chromosomes. Until the beginning of the 20th century, this direction was the only one. The use of a light microscope made it possible to obtain information about the behavior of chromosomes in mitotic and meiotic divisions (see Meiosis, Mitosis), facts about the constancy of the number of chromosomes in a given species, and special types of chromosomes. In the 20-40s of the 20th century, a comparative morphological study of chromosomes in different types of organisms, including humans, was predominantly developed in order to clarify the general principles of their organization, the characteristics of individual chromosomes and their changes in the process of evolution. Russian scientists S.G. Navashin, G.A.Levitsky, L.N. Delone, P.I. Zhivago, A.G. Andres, M.S. Navashin, A.A. rokof'eva-Belgovskaya, as well as foreign ones - Heitz (E. Heitz), Darlington (S. D. Darlington), etc. Since the 50s, an electron microscope has been used to study chromosomes. The study of morphological changes in chromosomes in the process of their genetic functioning began. In 1956, H. J. Tjio and A. Levan finally established the number of chromosomes in humans, equal to 46, described their morphological features in the metaphase of mitosis. Significant progress in the study of chromosomes was achieved in the 70s after the development of various methods for their staining, which made it possible to reveal the heterogeneity of the structure of chromosomes along the length in the meta phase of cell division.

Comparison of the behavior of chromosomes in meiotic division with the patterns of inheritance of characters (see Mendel's laws) laid the foundation for cytogenetic studies. In the late 19th - early 20th century Setton (W. Sutton), Boveri (Th. Boveri), Wilson (E. Century Wilson) laid the foundations of the chromosomal theory of heredity (see), according to which genes are localized in chromosomes and the behavior of the latter during the maturation of gametes and their fusion at the time of fertilization explains the laws of transmission of characters in generations. The theory was finally substantiated in cytogenetic experiments conducted on Drosophila (see) T. Morgan and his students, who proved that each chromosome is a group of genes linked inherited and arranged in a linear order, that gene recombination is carried out in meiosis (see Recombination ) homologous (identical) chromosomes.

The study of the biochemical nature of chromosomes, begun in the 30s-40s of the 20th century, was originally based on the cytochemical qualitative and quantitative determination of the content of DNA, RNA and proteins in the nucleus. Since the 50s, photo and spectrometry (see Spectrophotometry), X-ray structural analysis (see) and other physicochemical methods began to be used for these purposes.

Physicochemical nature of chromosomes

The physicochemical nature of chromosomes depends on the complexity of the organization of the biological species. The eukaryotic chromosome consists of a molecule of deoxyribonucleic acid (see), histone and non-histone proteins (see Histones), and also ribonucleic acid (see). The main chemical component of the chromosome, which contains genetic information in the structure of its molecule, is DNA. Under natural conditions, in some parts of the chromosome, DNA can be free of structural proteins, but basically it exists in the form of a complex with histones, and both in the interphase and in the metaphase, the weight ratio of DNA / histone is unity. The content of acidic proteins in chromosomes varies depending on their activity and the degree of condensation in the cell cycle. In the chromatin (see) of the interphase nucleus and at any stage of mitotic condensation, DNA exists in a complex with histones, and the interaction of these molecules creates the elementary structural particles of chromatin - nucleosomes. In the nucleosome, its central part is made up of 8 histone molecules of four types (2 molecules from each type). These are histones Н2А, Н2В, НЗ and Н4, interacting with each other, apparently, by the C-terminal regions of the molecules. The N-terminal regions of histone molecules interact with the DNA molecule in such a way that the latter is wound around the histone backbone, making two turns on one side and one on the other. There are about 140 DNA base pairs per nucleosome. Between adjacent nucleosomes there is a DNA segment varying in length (10-70 base pairs). When it is straightened, the DNA takes the form of a strand of beads. If the segment is folded, the nucleosomes are closely adjacent to each other, forming a fibril 10 nm in diameter. The structure of nucleosome particles is the principle of the organization of chromatin (see) both in the interphase and in the metaphase chromosome.

Individually distinguishable chromosomes are formed at the time of cell division, mitosis or meiosis, as a result of progressively increasing chromosome condensation. In the prophase of mitotic division, chromosomes are visible under a light microscope in the form of long and intertwined threads, therefore, individual chromosomes are indistinguishable throughout the entire length. In the prophase of the first meiotic division, chromosomes undergo complex specific morphological transformations, associated mainly with the conjugation of homologous chromosomes (see Chromosome conjugation) and genetic recombination (exchange of sites) between them. In pachytene (when conjugation ends), the alternation of chromomeres along the length of chromosomes is especially indicative, and the chromomeric pattern is specific for each chromosome and changes with condensation. Many chromosomes in oogenesis and the Y chromosome in spermatogenesis have high transcriptional activity. In some types of organisms, such chromosomes are called "lamp brushes". They consist of an axis built of chromomeres and interchromomeric regions, and numerous side loops - decondensed chromomers in a state of genetic functioning (transcription).

In the metaphase of cell division, chromosomes have the smallest length and are easy to investigate, therefore, a description of individual chromosomes, as well as their entire set in a cell, is given in relation to their state in this phase. The sizes of metaphase chromosomes in one and the same type of organisms differ greatly: chromosomes of a fraction of a micron have a dotted appearance, with a length of more than 1 micron they look like rod-shaped bodies. Usually these are formations bifurcated along the length, consisting of two sister chromatids (Fig. 2, 3), since chromosomes are reduplicated in metaphase.

Individual chromosomes of a set differ in length and other morphological characteristics. The methods used until the 70s ensured uniform staining of the chromosome along its length. Nevertheless, such a chromosome, as an obligatory structural element, has a primary constriction - a region where both chromatids are narrowed, apparently not separating from one another, and are poorly stained. This region of the chromosome is called the centromere, it contains a specialized structure - the kinetochore, which is involved in the formation of the filaments of the chromosome division spindle. According to the ratio of the sizes of the chromosome arms lying on both sides of the primary constriction, chromosomes are subdivided into three types: metacentric (with a medial constriction), submetacentric (the constriction is displaced from the middle), acrocentric (the centromere is located close to the end of the chromosome, Fig. 3). A person has all three types of chromosomes. The ends of the chromosomes are called telomeres. Along the length of the chromosomes, with varying degrees of constancy, there can be found not related to the centromere, the so-called secondary constrictions. If they are located close to the telomere, the distal portion of the chromosome separated by the constriction is called the satellite, and the constriction is called the satellite (Fig. 2). A person has ten chromosomes with a secondary constriction, all of them are acrocentric, satellites are localized in the short shoulder. Some secondary constrictions contain ribosomal genes and are called nucleolar-forming, because due to their functioning in the production of RNA in the interphase nucleus, a nucleolus is formed (see). Other secondary constrictions are formed by heterochromatic regions of chromosomes; in humans, of such constrictions, the most pronounced pericentromeric constrictions are in the 1st, 9th and 16th chromosomes.

The original method of using Giemsa and other chromosomal dyes produced uniform coloration along the entire length of the chromosome. Since the early 70s, a number of methods for staining and processing metaphase chromosomes have been developed, which made it possible to detect differentiation (division into light and dark stripes) of the linear structure of each chromosome along its entire length: with the help of akrikhin, acrihiniprita and other fluorochromes; G-staining (G - from the name Giemsa), obtained with the help of Giemsa dye (see Romanovsky - Giemsa method) after incubation of chromosome preparations under special conditions; R-color (R - from the English reverse reverse; chromosomes are colored back by G-color). The body of the chromosome is subdivided into segments of different intensity of staining or fluorescence. The number, position and size of such segments are specific for each chromosome, so any chromosome set can be identified. Other methods allow for differential staining of certain specific regions of chromosomes. It is possible to selectively stain with Giemsa dye heterochromatic regions of the chromosome (C-color; C - from centromere centromere), located near the centromere - C-segments (Fig. 4). In humans, C segments are found in the pericentromeric region of all autosomes and in the long arm of the Y chromosome. Heterochromatic regions vary in size in different individuals, causing chromosome polymorphism (see Chromosomal polymorphism). Specific colors make it possible to identify nucleolar-forming regions functioning in the interphase, as well as kinetochores, in metaphase chromosomes.

At the electron microscopic level, the main ultrastructure unit of interphase chromatin in transmission electron microscopy (see) is a thread with a diameter of 20-30 nm. The packing density of filaments is different in areas of dense and diffuse chromatin.

A metaphase chromosome on a section in a transmission electron microscope appears to be uniformly filled with fibrils 20-30 nm in diameter, which, depending on the section plane, have the appearance of round, oval or elongated formations. In prophase and telophase, thicker filaments (up to 300 nm) can be found in the chromosome. In electron microscopy, the surface of the metaphase chromosome is represented by chaotically stacked numerous fibrils of different diameters, visible, as a rule, on a short segment (Fig. 5). Filaments with a diameter of 30-60 nm predominate.

Variability of chromosomes in ontogeny and evolution

The constancy of the number of chromosomes in the chromosome set and the structure of each chromosome is an indispensable condition for normal development in ontogenesis (see) and preservation of biol. species. During the life of an organism, changes in the number of individual chromosomes and even their haploid sets (genomic mutations) or the structure of chromosomes (chromosomal mutations) can occur. Unusual chromosome variants, which determine the uniqueness of an individual's chromosome set, are used as genetic markers (marker chromosomes). Genomic and chromosomal mutations play an important role in the evolution of biol. species. The data obtained from the study of chromosomes make a great contribution to the taxonomy of species (karyosystematics). In animals, one of the main mechanisms of evolutionary variability is the change in the number and structure of individual chromosomes. The change in the content of heterochromatin in individual or several chromosomes is also important. A comparative study of the chromosomes of humans and modern apes made it possible, on the basis of the similarities and differences of individual chromosomes, to establish the degree of phylogenetic relationship of these species and to model the karyotype of their common closest ancestor.

Bochkov N. P., Zakharov A. F. and Ivanov V. I. Medical genetics, M., 1984; Darlington S. D. and La Cours L. F. Chromosomes, Methods of work, trans. from English, M., 1980, bibliogr .; Zakharov A.F. Human chromosomes (problems of linear organization ;, M., 1977, bibliogr .; Zakharov A.F. et al. Human chromosomes, Atlas, M., 1982; Kiknadze I.I. Functional organization of chromosomes, L. , 1972, bibliogr .; Fundamentals of human cytogenetics, under the editorship of A.A. ; Cell biology, A comprehensive treatise, ed. By L. Goldstein a. DM Prescott, p. 267, NY ao, 1979; Seuanez H. N, The phylogeny of human chromosomes, v. 2, B. ao 1979; Sharm a AK a. Sharma A. Chromosome techniques, L. ao, 1980; Therman E. Human chromosomes, NY ao, 1980.

A.F. Zakharov.

Chromosome is the organized structure of DNA and protein contained in cells. It is one piece of coiled DNA containing many genes, regulatory elements, and other nucleotide sequences. Chromosomes also contain proteins associated with DNA that are used to package DNA and control its functions. Chromosomal DNA encodes all or most of the genetic information in an organism; some species also contain plasmids or other extrachromosomal genetic elements.

Or Down's disease, also known as trisomy 21, is an inherited disorder caused by the presence of part or all of 3 copies of 21 chromosomes... Usually, it is associated with retardation of physical development, characteristic facial features, or mild to moderate intellectual ...

Chromosomes vary widely between different organisms. A DNA molecule can be round or linear, and can have anywhere from 100,000 to over 3,750,000,000 nucleotides in a long chain. Typically, eukaryotic cells (cells with nuclei) have large linear chromosomes, while prokaryotic cells (cells without specific nuclei) have smaller round chromosomes, although there are many exceptions to this rule. In addition, the cells may contain chromosomes of several types; for example, mitochondria in most eukaryotes and chloroplasts in plants have their own little chromosomes.

In eukaryotes, nuclear chromosomes are packed by proteins into a condensed structure called chromatin. This allows very long DNA molecules to fit into the cell nucleus. The structure of chromosomes and chromatin varies throughout the cell cycle. Chromosomes are an essential building block for cell division and must reproduce, divide and pass successfully to their daughter cells in order to ensure genetic diversity and the survival of their offspring. Chromosomes can be duplicated or non-duplicated. Non-duplicated chromosomes are single linear strands in which duplicated chromosomes contain two identical copies (called chromatids) united by a centromere.

Densification of duplicated chromosomes during mitosis and meiosis results in the classic four-arm structure. Chromosomal recombination plays a vital role in genetic diversity. If these structures are improperly manipulated through processes known as chromosomal instability and translocation, the cell can undergo mitotic catastrophe and die, or it can unexpectedly escape apoptosis, leading to cancer progression.

In practice, "chromosome" is a rather vague term. For prokaryotes and viruses lacking chromatin, the term genophore is more appropriate. In prokaryotes, DNA is usually organized in a loop that coils tightly around itself, sometimes accompanied by one or less round DNA molecules called plasmids. These small, round genomes are also found in mitochondria and chloroplasts, reflecting their bacterial origin. The simplest genophores are found in viruses: they are DNA or RNA molecules - short linear or round genophores that are often devoid of structural proteins.

Word " chromosome"Formed by the Greek words" χρῶμα "( chroma, color) and "σῶμα" ( soma, body) due to the property of chromosomes to undergo very strong staining with certain dyes.

History of the study of chromosomes

In a series of experiments begun in the mid-1880s, Theodore Boveri has definitely demonstrated that chromosomes are vectors of heredity. His two principles were subsequence chromosomes and individuality chromosomes. The second principle was very original. Wilhelm Roux suggested that each chromosome carries a different genetic load. Boveri was able to test and confirm this hypothesis. With the rediscovery of an early work by Gregor Mendel in the early 1900s, Boveri was able to mark the connection between the rules of inheritance and the behavior of chromosomes. Boveri influenced two generations of American cytologists: among them Edmund Beecher Wilson, Walter Sutton, and Theophilus Painter (in fact, Wilson and Painter worked with him).

In his famous book “ Cell in development and heredity Wilson tied together the independent work of Boveri and Sutton (circa 1902), calling the chromosomal theory of heredity the Sutton-Boveri theory (names are sometimes interchanged). Ernst Mayr notes that the theory has been hotly contested by some famous geneticists such as William Bateson, Wilhelm Johansen, Richard Goldschmidt, and T.H. Morgan, they all had a rather dogmatic mindset. In the end, complete proof was obtained from chromosome maps in Morgan's own laboratory.

Prokaryotes and chromosomes

Prokaryotes - bacteria and archaea - usually have one round chromosome, but there are many variations.

In most cases, the size of the chromosomes of bacteria can range from 160,000 base pairs in an endosymbiotic bacterium Candidatus Carsonella ruddii up to 12,200,000 bp in soil-dwelling bacteria Sorangium cellulosum... Spirochetes of the genus Borrelia are a remarkable exception to this classification, along with bacteria such as Borrelia burgdorferi(the cause of Lyme disease) containing one linear chromosome.

Structure in sequences

Chromosomes in prokaryotes have a smaller structure based on sequence than eukaryotes. Bacteria usually have one point (duplication origin) where duplication begins, while some archaea contain multiple points of duplication origin. Genes in prokaryotes are often organized into operons and usually do not contain introns, unlike eukaryotes.

DNA packaging

Prokaryotes do not have nuclei. Instead, their DNA is organized into a structure called a nucleoid. A nucleoid is a separate structure that occupies a specific area of ​​a bacterial cell. However, this structure is dynamic, maintained and transformed by the actions of histone-like proteins that bind to the bacterial chromosome. In archaea, the DNA in the chromosomes is even more organized, with the DNA packed into structures similar to the nucleosomes of eukaryotes.

Bacterial chromosomes tend to bind to the bacterial plasma membrane. In molecular biological applications, this allows its isolation from plasmid DNA by centrifuging the lysed bacterium and precipitating the membranes (and attached DNA).

Chromosomes of prokaryotes and plasmids are, like eukaryotic DNA, generally supercoiled. DNA must first be released in a weakened state in order to access transcription, regulation, and duplication.

In eukaryotes

Eukaryotes (cells with nuclei found in plants, yeasts, and animals) have large linear chromosomes found in the cell nucleus. Each chromosome has one centromere, with one or two arms protruding from the centromere, although in most circumstances these arms are not visible as such. In addition, most eukaryotes have one round mitochondrial genome, and some eukaryotes may have additional small round or linear cytoplasmic chromosomes.

In the nuclear chromosomes of eukaryotes, unconsolidated DNA exists in a semi-ordered structure where it is wrapped around histones (structural proteins) to form a composite material called chromatin.

Chromatin

Chromatin is a complex of DNA and protein found in the eukaryotic nucleus that packages chromosomes. The structure of chromatin varies significantly between different stages of the cell cycle, in accordance with the requirements of the DNA.

Interphase chromatin

During the interphase (the period of the cell cycle when the cell is not dividing), two types of chromatin can be distinguished:

• Euchromatin, which is composed of active DNA, that is, expressed as a protein.
• Heterochromatin, which is composed mostly of inactive DNA. It appears to serve structural purposes during chromosomal stages. Heterochromatin can be further classified into two types:
• Constitutive heterochromatin never expressed. It is located around the centromere and usually contains repeated sequences.
• Optional heterochromatin, sometimes expressed.

Metaphase chromatin and division

In the early stages of mitosis or meiosis (cell division), the chromatin strands become more and more dense. They cease to function as available genetic material (transcription stops) and become a compact transportable form. This compact shape makes the individual chromosomes visible, and they form the classic four-arm structure, with a pair of sister chromatids attached to each other at the centromere. Shorter shoulders are called " p shoulders"(From the French word" petit "- small), and longer shoulders are called " q shoulders"(Letter" q"Follows the letter" p»In the Latin alphabet; q-g "grande" is large). This is the only natural context in which individual chromosomes are visible with an optical microscope.

During mitosis, microtubules grow from centrosomes located at opposite ends of the cell and also attach to the centromere in specialized structures called kinetochores, one of which is present on each sister chromatid. A special DNA base sequence in the kinetochore region, together with special proteins, ensures long-term attachment to this region. Microtubules then pull chromatids to centrosomes so that each daughter cell inherits one set of chromatids. When the cells are divided, the chromatids unwind and the DNA can be transcribed again. Despite their appearance, chromosomes are structurally highly compacted, allowing these giant DNA structures to fit into cell nuclei.

Human chromosomes

Chromosomes in humans can be classified into two types: autosomes and sex chromosomes. Certain genetic traits are associated with a person's sex and are passed on through the sex chromosomes. Autosomes contain the rest of the inherited genetic information. Everyone acts the same way during cell division. Human cells contain 23 pairs of chromosomes (22 pairs of autosomes and one pair of sex chromosomes), giving a total of 46 per cell. In addition, human cells contain many hundreds of copies of the mitochondrial genome. Sequencing the human genome provided a lot of information about each chromosome. Below is a table that compiles statistics for chromosomes based on the Sanger Institute's human genome information in the VEGA (Vertebrate Genome Commentary) database. The number of genes is a rough estimate as it is based in part on gene prediction. The total length of the chromosomes is also a rough estimate based on the estimated size of the regions of inconsistent heterochromatins.

The number of chromosomes in various organisms

Eukaryotes

These tables give the total number of chromosomes (including sex) in the cell nucleus. For example, diploid human cells contain 22 different types of autosomes, each with two copies, and two sex chromosomes. This gives 46 chromosomes in total. Other organisms have more than two copies of their chromosomes, for example, hexaploid bread wheat contains six copies of seven different chromosomes, for a total of 42 chromosomes.

Normal members of certain eukaryotic species have the same number of nuclear chromosomes (see table). Other chromosomes of eukaryotes, that is, mitochondrial and plasmid-like small chromosomes, vary considerably in number, and there may be a thousand copies per cell.

Asexually reproducing species have one set of chromosomes, the same ones found in the cells of the body. However, asexual species can be haploid and diploid.

Sexually reproducing species have somatic cells (body cells) that are diploid, having two sets of chromosomes, one from the mother and the other from the father. Gametes, reproductive cells, are haploid [n]: they have one set of chromosomes. Gametes are obtained by meiosis of a diploid germ line cell. During meiosis, the corresponding chromosomes of the father and mother can exchange small parts of each other (crossing), and thus form new chromosomes that are not inherited only from one or the other parent. When the male and female gametes combine (fertilization), a new diploid organism is formed.

Some species of animals and plants are polyploid: they have more than two sets of homologous chromosomes. Plants that are important to agriculture, such as tobacco or wheat, are often polyploid compared to ancestral species. Wheat has a haploid number of seven chromosomes found in some cultivated plants as well as in wild ancestors. The more common pasta and bread wheat are polyploid, having 28 (tetraploid) and 42 (hexaploid) chromosomes, compared to 14 (diploid) chromosomes in wild wheat.

Prokaryotes

Prokaryotic species generally have one copy of each major chromosome, but most cells can easily survive with multiple copies. For example, Buchnera, a symbiont of aphids, has many copies of its chromosome, the number of which ranges from 10 to 400 copies per cell. However, in some large bacteria such as Epulopiscium fishelsoni, up to 100,000 copies of a chromosome may be present. The copy number of plasmids and plasmid-like small chromosomes, as in eukaryotes, fluctuates considerably. The number of plasmids in a cell is almost entirely determined by the rate of plasmid division — rapid division produces a high copy number.

Karyotype

Generally karyotype is a characteristic chromosomal complement of eukaryotic species. Preparing and studying karyotypes is part of cytogenetics.

Although DNA duplication and transcription is highly standardized in eukaryotes, the same cannot be said for their karyotypes which are usually quite volatile. The types of chromosome numbers and their detailed organization can vary. In some cases, there can be significant variation between species. Often there is:

1. oscillation between the two sexes;
2. oscillation between the germ line and the soma (between the gametes and the rest of the body);
3. fluctuation between members of the population due to balanced genetic polymorphism;
4. geographic variation between races;
5. mosaic or other anomalies

Also, fluctuations in the karyotype can occur during development from a fertilized egg.

The technique for determining the karyotype is usually called karyotyping... Cells can be blocked partially through division (in metaphase) in vitro (in a reaction tube) with colchicine. These cells are then stained, photographed, and arranged in a karyogram, with a set of ordered chromosomes, autosomes in length order, and sex chromosomes (here X / Y) at the end.

As with many sexually reproducing species, humans have special gonosomes (sex chromosomes, as opposed to autosomes). It is XX for women and XY for men.

Historical note

It took many years to study the human karyotype before the most basic question was answered: How many chromosomes are there in a normal diploid human cell? In 1912, Hans von Winewarter reported 47 chromosomes in spermatogonia and 48 in oogonia, including the XX / XO sex determination mechanism. Painter in 1922 was not sure about the diploid number of a person - 46 or 48, initially leaning towards 46. He later revised his opinion from 46 to 48, and correctly insisted that a person possesses the XX / XY system.

To finally solve the problem, new techniques were needed:

1. The use of cells in culture;
2. Preparing cells in a hypotonic solution, where they swell and spread chromosomes;
3. Delay of mitosis in metaphase with colchicine solution;
4. Crushing the preparation on the object holder, stimulating the chromosomes in a single plane;
5. Cutting the micrograph and organizing the results into an irrefutable karyogram.

Only in 1954 was the diploid number of a person confirmed - 46. Given the techniques of Winiwarter and Painter, their results were quite remarkable. Chimpanzees (the closest living relative of modern humans) have 48 chromosomes.

Delusions

Chromosomal abnormalities are abnormalities in the normal chromosomal content of a cell and are a major cause of genetic conditions in humans such as Down syndrome, although most abnormalities have little or no effect. Some chromosomal abnormalities do not cause disease in carriers, such as translocations or chromosomal inversions, although they can lead to an increased chance of having a baby with a chromosomal abnormality. An abnormal number of chromosomes, or chromosome sets called aneuploidy, can be fatal or give rise to genetic disorders. Families who may carry a chromosomal rearrangement are offered genetic counseling.

The recruitment or loss of DNA from chromosomes can lead to a variety of genetic disorders. Examples among humans:

• Feline scream syndrome, caused by the division of a portion of the short arm of chromosome 5. The condition is so named because children who are sick make shrill, cat-like screams. People with this syndrome have wide-set eyes, small head and jaw, moderate to severe mental health problems, and short stature.
• Down syndrome, the most common trisomy, is usually caused by an extra copy of chromosome 21 (trisomy 21). Characteristic features include decreased muscle tone, stocky build, asymmetrical cheekbones, slanted eyes, and mild to moderate developmental disabilities.
• Edwards syndrome, or trisomy of chromosome 18, is the second most common trisomy. Symptoms include slow movement, developmental disorders, and multiple congenital abnormalities that cause serious health problems. 90% of patients die in infancy. They are characterized by clenched fists and overlapping fingers.
• Isodicentric chromosome 15, also called idic (15), partial tetrasomy of the long arm of chromosome 15, or reverse duplication of chromosome 15 (inv dup 15).
• Jacobsen's syndrome is very rare. It is also called a disorder of the terminal deletion of the long arm of chromosome 11. Sufferers have normal intelligence or weak developmental disabilities, with poor speech skills. Most have a bleeding disorder called Paris-Trousseau syndrome.
• Klinefelter's syndrome (XXY). Men with Klinefelter syndrome are usually sterile, usually taller, and have longer arms and legs than their peers. Boys with the syndrome are usually shy and quiet and are more likely to have slowed down speech and dyslexia. Without testosterone treatment, some may develop gynecomastia during adolescence.
• Patau syndrome, also called D-syndrome or trisomy 13 of chromosome. Symptoms are somewhat similar to trisomy 18, without the characteristic folded arm.
• Small accessory marker chromosome. This means there is an extra abnormal chromosome. Properties depend on the origin of the additional genetic material. Cat eye syndrome and isodicentric 15 (or idic15) syndrome are caused by an extra marker chromosome, like Pallister-Killian syndrome.
• Triple X syndrome (XXX). XXX girls tend to be taller, thinner and more likely to be dyslexic.
• Turner syndrome (X instead of XX or XY). In Turner syndrome, female sexual characteristics are present, but underdeveloped. Women with Turner syndrome have a short torso, a low forehead, anomalies in the eyes and bones, and a concave chest.
• XYY syndrome. XYY boys are usually taller than their siblings. Like XXY boys and XXX girls, they are more likely to have learning difficulties.
• Wolf Hirschhorn syndrome, which is caused by partial destruction of the short arm of chromosome 4. It is characterized by severe growth retardation and severe mental health problems.

As a rule, a eukaryotic cell has one core, but there are binucleated (ciliates) and multinucleated cells (opaline). Some highly specialized cells lose their nucleus again (erythrocytes of mammals, sieve tubes of angiosperms).

The shape of the nucleus is spherical, elliptical, less often lobed, bean-shaped, etc. The diameter of the nucleus is usually from 3 to 10 microns.

1 - outer membrane; 2 - inner membrane; 3 - pores; 4 - nucleolus; 5 - hetero-chromatin; 6 - euchro-matin.

The nucleus is delimited from the cytoplasm by two membranes (each of them has a typical structure). Between the membranes there is a narrow gap filled with a semi-liquid substance. In some places, the membranes merge with each other, forming pores (3) through which the exchange of substances between the nucleus and the cytoplasm takes place. The outer nuclear (1) membrane from the side facing the cytoplasm is covered with ribosomes, which give it roughness, the inner (2) membrane is smooth. Nuclear membranes are part of the cell membrane system: the outgrowths of the outer nuclear membrane are connected to the channels of the endoplasmic reticulum, forming a single system of communicating channels.

Karyoplasm (nuclear juice, nucleoplasm)- the inner content of the nucleus, in which chromatin and one or more nucleoli are located. The composition of nuclear juice includes various proteins (including enzymes of the nucleus), free nucleotides.

Nucleolus(4) is a rounded dense body immersed in nuclear juice. The number of nucleoli depends on the functional state of the nucleus and varies from 1 to 7 or more. Nucleoli are found only in non-dividing nuclei; during mitosis, they disappear. The nucleolus is formed on certain parts of the chromosomes that carry information about the structure of rRNA. Such regions are called the nucleolar organizer and contain numerous copies of the genes encoding rRNA. Ribosome subunits are formed from rRNA and proteins coming from the cytoplasm. Thus, the nucleolus is an accumulation of rRNA and ribosomal subunits at different stages of their formation.

Chromatin- internal nucleoprotein structures of the nucleus, stained with some dyes and differing in shape from the nucleolus. Chromatin is in the form of lumps, granules and filaments. The chemical composition of chromatin: 1) DNA (30-45%), 2) histone proteins (30-50%), 3) non-histone proteins (4-33%), therefore, chromatin is a deoxyribonucleoprotein complex (DNP). Depending on the functional state of chromatin, there are: heterochromatin(5) and euchromatin(6). Euchromatin is genetically active, heterochromatin is genetically inactive regions of chromatin. Euchromatin under light microscopy is indistinguishable, weakly stained and represents decondensed (despiralized, untwisted) areas of chromatin. Heterochromatin under a light microscope looks like lumps or granules, intensely stains and represents condensed (spiralized, compacted) areas of chromatin. Chromatin is a form of existence of genetic material in interphase cells. During cell division (mitosis, meiosis), chromatin is converted into chromosomes.

Kernel functions: 1) storage of hereditary information and its transfer to daughter cells in the process of division, 2) regulation of cell life by regulating the synthesis of various proteins, 3) the place of formation of ribosome subunits.

Are cytological rod-shaped structures, which are condensed chromatin and appear in the cell during mitosis or meiosis. Chromosomes and chromatin are different forms of the spatial organization of the deoxyribonucleoprotein complex corresponding to different phases of the cell's life cycle. The chemical composition of chromosomes is the same as that of chromatin: 1) DNA (30-45%), 2) histone proteins (30-50%), 3) non-histone proteins (4-33%).

The basis of the chromosome is one continuous double-stranded DNA molecule; the DNA length of one chromosome can reach several centimeters. It is clear that a molecule of this length cannot be located in the cell in an elongated form, but undergoes folding, acquiring a certain three-dimensional structure, or conformation. The following levels of spatial packing of DNA and DNP can be distinguished: 1) nucleosomal (winding of DNA onto protein globules), 2) nucleomeric, 3) chromomeric, 4) chromonemal, 5) chromosomal.

In the process of converting chromatin into chromosomes, DNP forms not only spirals and supercoils, but also loops and superloops. Therefore, the process of chromosome formation, which occurs in prophase of mitosis or prophase 1 of meiosis, is better called not spiralization, but condensation of chromosomes.

1 - metacentric; 2 - submetacentric; 3, 4 - acrocentric. Chromosome structure: 5 - centromere; 6 - secondary constriction; 7 - satellite; 8 - chromatids; 9 - telomeres.

The metaphase chromosome (chromosomes are studied in the metaphase of mitosis) consists of two chromatids (8). Any chromosome has primary constriction (centromere)(5), which divides the chromosome into the shoulders. Some chromosomes have secondary constriction(6) and satellite(7). Satellite is a section of a short arm separated by a secondary constriction. Chromosomes that have a satellite are called satellite chromosomes (3). The ends of the chromosomes are called telomeres(nine). Depending on the position of the centromere, there are: a) metacentric(equal shoulder) (1), b) submetacentric(moderately unequal) (2), c) acrocentric(sharply unequal) chromosomes (3, 4).

Somatic cells contain diploid(double - 2n) set of chromosomes, sex cells - haploid(single - n). The diploid set of roundworm is 2, Drosophila - 8, chimpanzee - 48, crayfish - 196. Chromosomes of the diploid set are divided into pairs; chromosomes of one pair have the same structure, size, set of genes and are called homologous.

Karyotype- a set of information about the number, size and structure of metaphase chromosomes. An idiogram is a graphic representation of a karyotype. Representatives of different species have different karyotypes, one species is the same. Autosomes- chromosomes that are the same for male and female karyotypes. Sex chromosomes- chromosomes by which the male karyotype differs from the female.

The human chromosome set (2n = 46, n = 23) contains 22 pairs of autosomes and 1 pair of sex chromosomes. Autosomes are grouped and numbered:

Sex chromosomes do not belong to any of the groups and do not have a number. Sex chromosomes of women - XX, men - XY. X-chromosome - middle submetacentric, Y-chromosome - small acrocentric.

Chromosomes(Old Greek χρῶμα - color and σῶμα - body) - nucleoprotein structures in the nucleus of a eukaryotic cell (a cell containing a nucleus), which become easily noticeable in certain phases of the cell cycle (during mitosis or meiosis).

Chromosomes are a high degree of condensation of chromatin that is constantly present in the cell nucleus. Initially, the term was proposed to denote structures found in eukaryotic cells, but in recent decades, they increasingly talk about bacterial chromosomes. Most of the hereditary information is concentrated in chromosomes.

Eukaryotic chromosomes

Eukaryotic chromosomes have a complex structure. The basis of the chromosome is a linear (not closed in a ring) macromolecule of deoxyribonucleic acid (DNA) of considerable length (for example, DNA molecules of human chromosomes contain from 50 to 245 million base pairs). In an extended form, the length of a human chromosome can reach 5 cm. In addition to it, the chromosome includes five specialized proteins - H1, H2A, H2B, H3 and H4 (the so-called histones) and a number of non-histone proteins. The amino acid sequence of histones is highly conserved and practically does not differ in various groups of organisms. In the interphase, chromatin is not condensed, but even at this time its filaments are a complex of DNA and proteins. The DNA macromolecule wraps around octomeres (a structure consisting of eight protein globules) of histone proteins H2A, H2B, H3, and H4, forming structures called nucleosomes.

In general, the whole structure is somewhat reminiscent of beads. A sequence of such nucleosomes, connected by the H1 protein, is called a nucleofilament, or nucleosome strand, about 10 nm in diameter. In the early interphase (phase G1), the basis of each of the future chromosomes is one DNA molecule. In the synthesis phase (S), DNA molecules enter the replication process and duplicate. In the late interphase (phase G2), the base of each chromosome consists of two identical DNA molecules formed as a result of replication and connected to each other in the region of the centromeric sequence. Before division of the cell nucleus begins, the chromosome, represented at this moment by a chain of nucleosomes, begins to spiralize, or pack, forming a thicker chromatin fiber, 30 nm in diameter, with the help of the H1 protein. As a result of further spiralization, the chromatid diameter reaches 700 nm by the time of metaphase. The significant thickness of the chromosome (diameter 1400 nm) at the metaphase stage allows, finally, to see it through a light microscope.

The condensed chromosome looks like the letter X (often with unequal arms), since the two chromatids resulting from replication are still connected to each other in the centromere region. Each cell of the human body contains exactly 46 chromosomes... Chromosomes are always paired. In a cell there are always 2 chromosomes of each type, the pairs differ from each other in length, shape and the presence of thickenings or constrictions. In most cases, the chromosomes are different enough for a cytologist to distinguish between pairs of chromosomes (23 pairs in total).

It should be noted that in all somatic cells (all cells of the body, except for sex) chromosomes in pairs are always the same in size, shape, location of centromeres, while the sex chromosomes (23rd pair) in men are not the same (XY), but women have the same (XX). Chromosomes in a cell under a microscope can only be seen during division - mitosis, during the metaphase stage. These chromosomes are called metaphase. When the cell is not dividing, the chromosomes look like thin, dark-colored filaments called chromatin.

Chromatin is a deoxyribonucleoprotein that is detected under a light microscope in the form of thin filaments and granules. In the process of mitosis (cell division), chromatin by spiralization forms clearly visible (especially in metaphase) intensely staining structures - chromosomes. The metaphase chromosome consists of two longitudinal strands of deoxyribonucleoprotein - chromatids, connected to each other in the region of the primary constriction - centromere.

The centromere is a specially organized chromosome region, common to both sister chromatids. The centromere divides the chromosome body into two arms. Depending on the location of the primary constriction, the following types of chromosomes are distinguished: equal arms (metacentric), when the centromere is located in the middle, and the arms are of approximately equal length; unequal arms (submetacentric), when the centromere is displaced from the middle of the chromosome, and the arms are of unequal length; rod-shaped (acrocentric), when the centromere is displaced to one end of the chromosome and one shoulder is very short. There are also point (telocentric) chromosomes, they have one shoulder missing, but they are not in the karyotype (chromosome set) of a person. In some chromosomes, there may be secondary constrictions that separate a region called a satellite from the body of the chromosome.

The study of the chemical organization of the chromosomes of eukaryotic cells has shown that they consist mainly of DNA and proteins. As has been proven by numerous studies, DNA is a material carrier of the properties of heredity and variability and contains biological information - a program for the development of a cell, an organism, recorded using a special code. Proteins make up a significant part of the chromosome substance (about 65% of the mass of these structures). The chromosome as a complex of genes is an evolutionarily developed structure inherent in all individuals of a given species. The mutual arrangement of genes in the chromosome plays an important role in the nature of their functioning. A change in the number of chromosomes in a person's karyotype can lead to various diseases.

Most frequent chromosomal disease a person has Down syndrome due to trisomy (to a pair of normal chromosomes one more is added, the same extra one) on the 21st chromosome. This syndrome occurs with a frequency of 1-2 per 1000. Often, trisomy on 21 pairs of chromosomes is the cause of fetal death, but sometimes people with Down syndrome live to a considerable age, although in general their life expectancy is reduced.

Known trisomies on the 13th chromosome - Patau syndrome, as well as on the 18th chromosome - Edwards syndrome, in which the viability of newborns is sharply reduced. They die in the first months of life due to multiple developmental defects. Quite often, a person has a change in the number of sex chromosomes. Among them, X monosomy is known (of a pair of chromosomes, only one (X0) is present) is Shereshevsky-Turner syndrome... Less common is trisomy X and Klinefelter's syndrome(XXY, XXXY, XXY, etc.). People with a change in the number of sex chromosomes in the presence of the Y chromosome develop in the male pattern. This is due to the fact that the factors that determine the male type of development are located on the Y chromosome. Unlike mutations of autosomes (all chromosomes, except for sexual ones), mental defects in patients are not so pronounced, in many it is within normal limits, and sometimes even above average. At the same time, they constantly have violations of the development of the genital organs and growth. Malformations of other systems are less common.