What kind of human cells are subject to mitosis



      Chromosomes (from Greek: χρῶμα = Chroma, "color" and σῶμα = Soma, "body", ie "color body") are structures that contain genes and thus genetic information. They are made up of DNA that is packed with many proteins. This mixture of DNA and proteins is also known as chromatin.

Chromosomes come in the cell nuclei of the cells of eukaryotes (living things With Nucleus), to which all animals, plants and fungi belong. Prokaryotes (living beings without Cell nucleus), i.e. bacteria and archaea, do not have chromosomes in the classical sense, but one or more, mostly circular DNA molecules, which are sometimes referred to as "bacterial chromosomes", although they do not have much in common with eukaryotic chromosomes. Almost all genes in eukaryotes are on the chromosomes. A few are based on DNA in the mitochondria and, in plants, also in the chloroplasts. In the mitochondria and chloroplasts of the eukaryotes, the DNA is also circular, similar to the bacterial chromosome.

The X-like shape of the chromosomes, which predominates in most representations, occurs only in a short section during the cell nucleus division (mitosis), namely in the metaphase (see first illustration). In this condensed state, the chromosomes can be seen under the light microscope without any particular coloration. Between nuclear divisions, in the interphase, chromosomes exist in the cell nucleus in a “relaxed”, decondensed state in which they can only be detected as separate units by using a special detection technique (fluorescence in situ hybridization). The DNA can only be read and duplicated in this decondensed state. In the interphase, each chromosome in the cell nucleus occupies a delimited area, a chromosome territory (see figures).

history

The name chromosome was proposed in 1888 by the anatomist Heinrich Wilhelm Waldeyer after Walther Flemming had introduced "chromatin" for the stainable substance in the cell nucleus a few years earlier. In 1906 Oscar Hertwig was still using the term “core segments”, which was intended to clarify that when the core is divided (mitosis) “the chromatin is broken down into segments”. Another old name that was used in parallel to "Chromosome" for a while is "Kernschleife", for example in Karl Heider (1906)

The story of the Discovery of the chromosomes and their function cannot be separated from the previous discovery of the cell nucleus (see there first).

In 1843 Carl Wilhelm von Nägeli described “transitory cytoblasts”, which were presumably chromosomes, but did not recognize their significance. With today's knowledge, images from the works of other researchers can also be interpreted as chromosomes or mitotic cell division (Matthias Schleiden, 1846; Rudolf Virchow, 1857; Otto Bütschli, 1873).

In 1873 Anton Schneider described in platelets that the cell nucleus "transformed into a heap of fine, curly curved threads that become visible on the addition of acetic acid. Instead of these thin threads, thick strands appeared, at first irregular, then arranged in a rosette, which lies in a plane (equatorial plane) going through the center of the sphere.“The indirect nuclear division was discovered - but not yet understood. In 1882 Walther Flemming assumed that the "core threads" only separate from one another from a previously continuous thread during the early phase of core division. Although he observed a longitudinal splitting of the chromosomes at a later point in time (now known as metaphase), he assumed that the entire Chromosome (with both chromatids) later (today: anaphase) moved in the direction of a spindle pole. He also did not rule out the possibility that cell nuclei could, at least in some cases, also form anew, i.e. not through division from existing nuclei. Both together make it clear that the importance of chromosomes for inheritance has not yet been recognized.

This meaning was suggested shortly afterwards by Wilhelm Roux (1883). From the complexity of the processes involved in the division of the nucleus (instead of a simple constriction) in combination with a selection advantage required from an evolutionary theoretical point of view, he concluded that a very even distribution of chromatin among the daughter cells was extremely important and that this importance could only be based on the fact that that chromatin must have "an uncommon variety ... of qualities". Today we can easily explain this “complicated composition of chromatin” postulated by him with the presence of genes. In the following year several authors (L. Guignard, Emil Heuser and Edouard van Beneden) described the division of the daughter chromatids into the daughter cell nuclei.

Since the chromosomes were not visible during the interphase, it was initially unclear whether they disintegrated after a nucleus division and formed anew before each nucleus division, or whether they survived in the nucleus as separate units. The latter idea was called the doctrine of the preservation of the individuality of the chromosomes and proposed by Carl Rabl (1885). He was the first to firstly determine a constant number of chromosomes in different mitoses of a tissue and secondly to conclude that the chromosomes must also be present in the interphase and thus continuously. However, he initially left open the possibility that this number could be different in different tissues. Rabl was also the first to assume that each chromosome in the interphase nucleus forms its own territory.

The idea of ​​chromosome continuity by no means met with unanimous support. Oscar Hertwig (1890, 1917) was an important opponent. Theodor Boveri, on the other hand, endorsed Rabl's ideas and supported them with further experimental findings (1904, 1909). Also in the 1880s, August Weismann developed his germplasm theory (see also there), in which he assumed that the genetic material was (only) located in the chromosomes. Important conclusions were that inheritance only takes place via the germline and that inheritance of acquired traits should be rejected. What later proved to be largely correct was fiercely controversial at the time. A relentless criticism can be found, for example, in "Meyers Konversationslexikon von 1888" under the keyword heredity (online here).

In 1900 Mendel's rules were rediscovered and confirmed, and as a result the new science of genetics developed, in the context of which the connection between chromosomes and heredity was shown many times. For example, Thomas Hunt Morgan was able to attend in 1910 Drosophila melanogaster prove that the chromosomes are the carriers of the genes. In 1944, Oswald Avery (see there) showed that the actual genetic molecule is DNA, and not proteins in the chromosomes.

The further story up to 1950 (elucidation of the structure of the DNA) is described in the article Chromosome Theory of Inheritance. A timeline of some important discoveries can be found in the article Chromatin.

In 2000, two international teams of scientists largely deciphered the human genome; in 2003, 99 percent were sequenced. Chromosome 1, the last of the 24 different human chromosomes, was precisely analyzed in 2005/06 (99.99%). More than 160 scientists from Great Britain and the USA published this joint work [1].

Structure and structure of the chromosomes

Components

In the simplest case it contains a chromosome one continuous DNA thread to which Histones and other proteins are attached (see below). The DNA thread is sometimes referred to as a DNA molecule, although the DNA double helix at hand is strictly speaking two single-stranded molecules (see deoxyribonucleic acid). Unique names are DNA double strand or DNA double helix. The case described with one DNA double strand per chromosome always occurs immediately after a nuclear division; in most animals and plants also in all cells that can no longer divide (exception: polytane chromosomes in insects, see also below) and in cells that temporarily no longer grow, i.e. are in the G0 phase (see cell cycle) . In the case described, the whole chromosome consists of one Chromatid.

When a cell grows to divide later, the DNA has to be doubled ("replicated") in a certain section of the cell cycle (S-phase). This is necessary so that both daughter nuclei can later receive the entire genetic material, i.e. copies of all chromosomes. After DNA duplication, each chromosome has two identical double strands of DNA. These two double strands are packed with proteins spatially separated from each other: two Sister chromatids arise. During nuclear division (mitosis), the two sister chromatids of a chromosome are microscopically visible as units that run parallel but are separated by a narrow gap (see diagram on the right and first illustration of the article). At one point that Centromere or centromere, each chromosome is narrower at this point than in the rest of the process: Here the sister chromatids are still connected. In the further course of mitosis (at the transition from metaphase to anaphase, see below) the two sister chromatids are separated and distributed to the newly emerging cell nuclei: The chromosomes in these new nuclei now consist of a chromatid again. According to this, a chromatid always contains exactly one DNA double strand while a chromosome contains one or two DNA double strands depending on the phase of the cell cycle and accordingly consists of one or two chromatids. (Exception: the polytene chromosomes mentioned, which can contain over a thousand double strands.)

The centromere divides the chromatids into two poor divided. Depending on the position of the centromere, one speaks of metacentric (Centromere in the middle), acrocentric (in the end, the shorter arm is very small) or submetacentric (between middle and end) chromosomes. The shorter arm is called p-arm (petite, French for small), the longer than q arm designated. As in the schematic drawing, chromosomes are generally shown with the short arms facing up.

The ends of the chromosomes are called Telomeres (Unique: telomere). They contain a short, identically repeating DNA sequence (in humans TTAGGG). There the chromosomes become a little shorter each time they are doubled. The telomeres therefore play an important role in the aging process. In addition to centromere and telomeres, starting points for DNA duplication (replication) are the third essential component of a chromosome (see ARS element).

In humans, the short arms of the acrocentric chromosomes contain genes for ribosomal RNA. These short arms can be extended by a satellite in condensed metaphase chromosomes, so that satellite chromosomes (SAT chromosomes) are available (not to be confused with satellite DNA). The genes for the ribosomal RNA are present in many copies lying one behind the other in tandem. The nucleolus is formed on these in the interphase cell nucleus. Hence they are also known as nucleolus organizing regions (NOR).

Chromosomes during normal nuclear division (mitosis)

This section briefly describes what happens during mitosis. These are reproduced in more detail in the separate article Mitosis.

  • Prophase: In this first stage of mitosis, the chromosomes increasingly condense. They are transformed from an accessible source of genetic information into a compact form of transport that is no longer legible. The nuclear membrane is dissolved. This is sometimes called the start of an additional phase to the Prometaphase seen.
  • Metaphase: The chromosomes migrate into the equatorial plane of the cell and form the metaphase plate there. Up to this point each chromosome consists of two chromatids.
  • Anaphase: The spindle apparatus ensures the separation of the chromatids of each chromosome and their transport perpendicularly away from the metaphase plate, to two opposite cell poles. For this purpose, microtubules are attached to the kinetochores of the centromeres as well as to the cell poles.
  • Telophase: After completion of the anaphase movement, the nuclear envelope around the chromosomes is newly formed. Decondensation begins. The newly emerging cell nucleus now contains single-chromatid chromosomes.

After the nucleus division, cell division, cytokinesis or cytokinesis, usually takes place, but this is no longer counted as mitosis.

G, R and other chromosome bands

In the middle of the 20th century, techniques were developed to "spread" the chromosomes from cells that are in the metaphase: in the resulting Metaphase preparation If the chromosomes of a cell are next to each other on a slide so that they can be counted and compared with each other under the microscope (see first figure above). In well-made preparations, the individual chromosomes have the often shown X-like shape. With the classic staining methods such as Giemsa staining, chromosomes are stained evenly over their entire length. For this reason, it was initially difficult or impossible to reliably differentiate between chromosomes of similar size. Around 1970 it was discovered that some areas of the chromosomes no longer accept the Giemsa dye if the chromosomes were previously treated with trypsin. The evoked G-straps alternating colored (the G bands, G for Giemsa) and unstained sections (the R bands, R for reverse) arose along the chromosomes. The banding pattern enables unambiguous identification of all chromosomes in humans and many animals. The material basis for the different coloring behavior of the bands, i.e. the question of why some areas no longer absorb the dye after trypsin treatment, has not yet been clarified. However, it turned out that the G and R bands differ in some properties.

  R bands contain an above-average number of genes, an above-average number of G-C base pairings and are doubled early during the replication of the chromosomes. In humans they are rich in Alu sequences (see there and figure on the right).

G bands are poor in genes, the number of G-C base pairs is below average, (but they have more A-T pairs; see deoxyribonucleic acid) and they are replicated rather late during the duplication of the chromosomes. In humans, they are rich in L1 elements (see LINE (Genetics)).

Other gang types are sometimes used C bands (the centromere regions) and T-bands differentiated. The latter are a subgroup of the R bands, are particularly rich in genes and are often close to the telomeres, hence the name.

The number of R and G bands depends on the degree of condensation of the chromosomes. In the metaphase all human chromosomes together have about 400 of these bands, while in the not yet so strongly condensed prophase chromosomes up to 850 bands can be distinguished.

  nomenclature: In order to enable an exact designation of all chromosomal regions, standardized designation systems have been introduced for humans and some other organisms. In humans, each band has a name made up of the following elements: the number of the chromosome, p or q for the respective arm, and numbers that count up from the centromere. For a finer distinction, the numbers can have several digits. The band 3q26.31 is therefore a sub-band of 3q26. The designation “3q” accordingly stands for the entire long arm of chromosome 3. Centromere regions are also designated with c (3c). For the sake of simplicity, telomer areas are often referred to as tel (approx. 3ptel or 3qtel) and areas close to telomeres as ter (3pter). Schematic representations of the standard bands are called Idiograms. Examples are shown in the illustration to the right and on the Ensembl website[2] to see. In idiograms, G bands are always shown in dark, R bands in white. Areas made up of repetitive elements are sometimes shown hatched. An ordered arrangement of all the mitotic chromosomes from a cell is called Karyogram labeled (figure below). The Karyotype of a living being indicates how many and, if applicable, which chromosomes this individual has. The karyotype of a woman is given as 46, XX, that of a man as 46, XY (see below, gender determination)

Size and gene density

The human genome, i.e. the total length of the DNA, comprises around 3.2 Gbp (= gigabase pairs or billions of base pairs) with 23,700 genes found so far[2]. Humans have two copies of the genome (2n), one from the mother and one from the father, which are present in each nucleus. The DNA molecular model results in a length of 3.4 nanometers (billionths of a meter) for 10 base pairs in the double helix. From this it can be extrapolated that the total length of the DNA in every human cell is over 2 meters.In humans, these are distributed over 2n = 46 chromosomes, so that one chromosome contains an average of around 140 Mbp (= megabase pairs, millions of base pairs) and thus a DNA thread almost 5 cm in length with a little over 1000 genes. However, chromosomes during nuclear division are only a few micrometers (millionths of a meter) in length. They are therefore shortened or “condensed” by a factor of around 10,000. Chromosomes are hardly longer in the interphase nucleus either. The chromosome territories present here are mainly created by the decondensation of the daughter chromatids in width. While a daughter chromatid in the metaphase has a diameter of about 0.6 micrometers, a chromosome territory can occupy a circumference which corresponds approximately to its length. However, chromosome territories can be very irregular in shape. From the numerical values ​​given, it becomes clear that chromosomes must be strongly compacted, i.e. unfolded, even during the interphase (see next chapter).

Chromosome 1, the largest human chromosome, has 247 Mbp, the shortest chromosome 21 has less than a fifth of it, namely 47 Mbp. The genes are unevenly distributed between the chromosomes. The relatively gene-rich chromosome 19 contains over 3000 genes on 64 Mbp, while the gene-poor chromosome 18 only contains around 600 genes on 76 Mbp (see also figure “gene-poor and gene-rich regions” above). However, the poorest is the Y chromosome, which only contains around 200 genes at 58 Mbp. (Sizes and densities in this section of [2], As of September 2006).

At the house mouse (Mus musculus) the differences between the chromosomes are smaller. The 2.6 Gbp genome with 24400 described genes is distributed over 20 different chromosomes (2n = 40) between 197 Mbp (chromosome 1) and 61 Mbp (chromosome 19) or 16 Mbp (Y chromosome)[3].

The length of the individual chromosomes in other mammals varies greatly, depending on the number. Some have few, large chromosomes (e.g. the Indian muntjac, (Muntjac muntjacus) 2n = 6 in the female and 2n = 7 in the male), others many small ones (e.g. in the rhinoceros, (Diceros bicornis) 2n = 84). However, the exact lengths in base pairs are only known in a small number of animals.

Chromosomes of extremely different sizes appear in lizards and birds (see figure). The Macrochromosomes resemble mammalian chromosomes in terms of size. The chicken chromosome 1 (Gallus gallus) contains 188 Mbp, for example. But there are also many Microchromosomeswhose size can be less than 1 Mbp[4]. The transition from macro to microchromosomes is often fluid, so that the two groups are sometimes differentiated from one another. In the chicken the macrochromosomes can e.g. B. comprise chromosomes 1-8 or 1-10. For a visual size comparison see Ensembl[4]. The sizes in Mbp are also taken from there. The terms macro and microchromosomes were introduced by Theophilus S. Painter in 1921, who studied spermatogenesis in lizards[5].

Molecular structure and hierarchy of the packaging levels

In the previous section it is shown that the DNA has to be very coiled or “condensed” both during nuclear division and in the interphase. However, it is still largely unclear how this packaging is organized. Basic structural proteins, the Histones. DNA, histones and other proteins each make up about a third of the chromosomal mass. This is also known as chromatin. The use of the term chromatin is particularly common for descriptions of the cell nucleus in the interphase, since individual chromosomes cannot be distinguished from one another without special staining (fluorescence in situ hybridization).

On the lowest packaging level, the DNA thread is in Nucleosomes wound, which contain eight histone molecules (see fig., sub-picture (2)). Nucleosomes have a diameter of around 10 nanometers (nm), which is why this is also referred to as the 10 nm fiber. Their structure is often compared to a pearl necklace, in which the thread is however wrapped around the pearl. 146 base pairs of DNA are wound up in a nucleosome, plus linker DNA between the nucleosomes. The 10 nm fiber can be detected in the electron microscope, as can the next higher packaging level, the 30 nm fiber. The internal structure of the 30 nm fiber, i.e. how it is assembled from the 10 nm fiber by being unfolded, is, however, already unclear, just like all higher packaging levels. Various models are discussed for the latter. In the loop model, it is assumed that the 30 nm fiber runs in large loops that are attached to a kind of backbone. In the Chromonema model, on the other hand, it is assumed that the 30 nm fiber is thickened by further unfolding, resulting in sections 120 nm and thicker [6]. How the structural change from the interphase state to the prophase chromosome takes place is also unclear. When it comes to the transition from the prophase chromosomes to the even more condensed metaphase chromosomes, there seems to be agreement that this is a spiral-shaped winding.

The condensation of the chromosomes or the chromatin is not uniform within the cell nucleus. Some areas of the nucleus are particularly strongly colored by DNA dyes. The condensation is particularly strong here. These areas are called heterochromatin, whereas less colored areas are called euchromatin.

Giant chromosomes

Two types of giant chromosomes are known, polytene chromosomes and lamp brush chromosomes.

Polytene chromosomes

The polytene chromosms represent a special feature with regard to the internal chromosomal structure. They are known from various insects and are particularly good in the fruit fly Drosophila melanogaster and in Chironimus examined. They are created by several rounds of DNA doubling without subsequent core division (endoreduplication). In contrast to “normal” polyploidy, in polytene chromosomes the multiple replicas of DNA threads from both homologous chromosomes (i.e. the copy inherited from the father and the copy inherited from the mother) are arranged in parallel, similar to a cable strand. All copies of a gene are therefore next to each other. Polytene chromosomes are described in more detail in the article Giant Chromosome.

Lamp brush chromosomes

Another form of very large chromosomes is found in the ova of amphibians. Because they resemble a bottle or lamp brush from the microscopic point of view, they were called lamp brush chromosomes. They are described in a separate article.

Polytene chromosomes in a salivary gland cell of Chironimus. Walther Flemming, 1882. "Chromatic thread, which is comparable to a bottle brush" (according to today's terminology a Lamp brush chromosome) from the core of an egg cell of the water salamander (Triton). Click here to see the entire board. Oscar Hertwig, 1906.

Sex determination by chromosomes and their consequences

Sex determination

While in some animal species sex is determined by environmental conditions such as temperature during embryonic development (e.g. crocodiles), in others it is determined by the inherited chromosomes: They have a chromosomal sex. Different groups of animals have produced different methods of determining chromosomal sex, and in some cases similar systems have been developed independently of one another[7].

Mammals and thus also humans, each with a few lizards, amphibians and fish as well as the fruit fly Drosophila melanogaster have a XY / XX system: Females have the same sex chromosome twice (=Gonosome), namely two X chromosomes. They are therefore homozygous for the gonosomes. Males, on the other hand, have an X chromosome and a Y chromosome. This state is called hemizygous. An X chromosome is always passed on from the mother, and either an X or a Y chromosome from the father. All other chromosomes that Autosomes, are available in two copies each. For People was able to show on the basis of patients with a deviating number of chromosomes that whether a Y chromosome is present or not is decisive for gender expression. This is where the SRY gene is located, which is required for male development. In Turner syndrome, those affected have only one X chromosome and no Y chromosome. You develop into a woman. At Drosophila on the other hand, it is the case that individuals with an X and without a Y chromosome develop into males. The ratio of autosomes to X chromosomes is crucial here. If it is 1, females will result, 2 will result in males. In some species there are several different X chromosomes and / or several different Y chromosomes. The platypus can be taken as an extreme example, in which the females have ten X chromosomes (X1-X5, 2 times each) and the males five different X and five different Y chromosomes[8]. The XY / XX system in mammals is fully described in the article Sex Determination.

At the ZW / ZZ system the females are hemizygous, they have a W and a Z chromosome, while the males have two Z chromosomes. It is found in birds, most snakes, and a few lizards, fish, and amphibians each.

The worm Caenorhabditis elegans, a nematode, has a XX / X0 system: There are two sexes, hermaphrodite and male. While the hermaphrodites have two X chromosomes, the rare males have only one of them. But there is no other sex chromosome, so the males have one chromosome less, 9 instead of 10. As with Drosophila the ratio of autosomes to X chromosomes is crucial.

In over 2000 species of hymenoptera (ants, bees, wasps), males hatch from unfertilized eggs, which are therefore haploid[7]. They therefore have only half as many chromosomes as the diploid females (Haplo-diploidy, see parthenogenesis). In the case of the well-studied bees, it turned out that, similar to humans, a certain gene is ultimately decisive for determining sex. If it is available in two different versions (in the case of the fertilized eggs), females arise. If it is only available in one version (in the case of unfertilized eggs), males result. Inbreeding can lead to this gene being present in two identical versions in fertilized eggs. Then diploid males emerge[7]. However, these are eaten by the workers after they hatch from the egg.

Consequence of hemizygosity

While mammalian females have two X chromosomes, the males only have one X and one Y chromosome each, as just described, they are hemizygous. As a result, if there is a genetic defect on the only existing X chromosome, it cannot be caught by a functioning copy on the other chromosome, as is the case with females. Therefore, there are a number of hereditary diseases in humans that practically only occur in men. The best-known examples are a form of hemophilia, Duchenne's muscular dystrophy and red-green blindness.

Dose compensation

As a further consequence of the chromosomal sex determination, one chromosome is present twice in one of the sexes and only present once in the other. In order to prevent twice as much gene product from being produced here as in the opposite sex, different groups of animals have developed different strategies for “dose compensation”.

In humans, mice and possibly mammals in general, one of the two becomes female X chromosomes inactivated. The inactive X chromosome undergoes a number of changes that make it a Barr body that can be detected by light microscopy (see illustration). This epigenetic process is described in detail in the articles X-Inactivation and Sex Chromatin.

In the worm Caenorhabditis elegans on the other hand, both X chromosomes are equally downregulated in the hermaphrodite. In the fruit fly Drosophila melanogaster there is no X-inactivation. Instead, the single X chromosome in the male is read twice as strongly as in the female.

In birds, the type of dose compensation is still not understood. It is possible that the single Z chromosome is read more intensely in females[9].

Chromosome number

 

Karyotype: The chromosomes of an individual

All of the different chromosomes that appear in an individual are collectively known as a karyotype. The individuals of the same species and of the same sex usually have the same set of chromosomes and thus the same karyotype. An exception are the B chromosomes, which occur in some species and which can be present in different numbers in different individuals and also in different body cells (see below). For better differentiation from the B chromosomes, the normal chromosomes can be referred to as A chromosomes.

In these, too, the type and - less often - the number of chromosomes can differ between the sexes; they then have a different karyotype (see also sex determination above). For example, humans have 46 chromosomes in both sexes. The karyotype is given as 46, XX for women and 46, XY for men. Karyotypes are determined with the help of karyograms (see below).

In many cases, including humans, there are always two in the karyotype, apart from the sex chromosomes in the hemizygous sex homologous chromosomesnamely those that carry the same genes. In these cases one speaks of a double or diploidChromosome set, which is also abbreviated with 2n. In the case of sexually reproducing organisms, one was inherited from both parents.

Passing on the chromosomes to the next generation

In order to prevent a steady increase in the number of chromosomes from generation to generation, a Reduction division occur. This is part of the meiosiswhich is described in a separate article. During meiosis, crossing over also leads to one Recombination of homologous chromosomes. This creates genetically newly composed chromosomes that differ from those of the parent organisms. Which of the recombined chromosomes together in the resulting cells with a chromosome set (haploid Cells), i.e. which paternal and maternal sections come together, is random. In diploid Animals haploid germ cells (egg cells and sperm) are generated. A deviation from a random distribution of chromosomes found in a few animal species occurs in the Hybridogenesis on (see there). The germ cells can merge again to form the first cell of a new living being, the zygote. At plants and Unicellular organisms haploid and diploid generations can alternate (see generation change). Sometimes the haploid generation is dominant and the diploid status is very short.

Non-diploid number of chromosome sets

Occasionally the opinion is found that all higher animals and plants have two sets of chromosomes, that is, they are diploid. However, this is not the case. While the majority of animals and many plants are diploid, there are quite a few with others Degrees of ploidy.

Haploids Individuals occur, for example, as just described when the generation of plants changes. In addition, haploid males are found in a number of insect species (see above, sex determination) and probably also in some mites. It's a case of haploid female Animals known: the mite species Brevipalpus phoenicis, a pest of tropical crops, consists only of haploid females that reproduce parthenogenetically. According to one study, the males are actually genetic and transformed into females by infection with bacteria[10]. Feminization through bacterial infection is also known in other arthropods, mostly Wolbachia.

Some species have more than two sets of chromosomes and thus higher degrees of ploidy. These are called triploid = 3n, tetraploid = 4n, hexaploid = 6n or generally as polyploid designated. In plants, the haploid chromosome number of an organism is usually denoted by x (base number). Diploid plants then have 2x chromosomes, tetraploid 4x etc. The genome of a tetraploid plant with the base number x = 7 is then described as 2n = 4x = 28.[11]

Tetraploidy is probably the second most common degree of ploidy after diploidy. It has been observed in many flowering plants, insects and also amphibians. Tetraploidy can occur by preventing cells from dividing after chromosome doubling. Many crops, e.g. B. in the case of grains, created by polyploidization from diploid wild forms.

Even higher degrees of ploidy occur in plants. They can arise, for example, when two species are crossed and the children keep all the chromosomes from their parents. One then speaks of addition bastards. Hexaploid is for example the modern seed wheat (see here for the origin).

Triploids Individuals can arise when diploid and tetraploid individuals mate. This is possible when both are closely related species.Typically, however, triploid individuals will be sterile because an odd number of chromosome sets creates difficulties in pairing the chromosomes during meiosis. Exceptions, i.e. reproductive triploid individuals, were discovered in amphibians. Sometimes diploidy, tetraploidy and also triploidy occur in closely related species or in the same species next to each other. In the water frog, one of the sets of chromosomes is specifically eliminated before meiosis (hybridogenesis, see there). A locally limited, triploid population of green toad was found in Pakistan, in which a set of chromosomes is also specifically eliminated prior to meiosis[12].

In theory at least, there can be a smooth transition from tetraploid to diploid, for example. In a tetraploid living being, as described above, there are all chromosomescouples duplicated. Changes to one of the two pairs, for example the loss of individual genes, can therefore be tolerated. The gene copies on the two pairs can also develop apart during further evolution and take on different functions. Chromosome mutations (see below) in only one of the two pairs are also possible. If many such changes come together over time, the originally identical pairs of chromosomes have developed so far apart that it is no longer possible to speak of four-fold chromosome sets: there is diploidy again. Two rounds (hence the “2R hypothesis”) of such genome duplications have been proposed for the early history of vertebrate formation, so that today's diploid vertebrates would have evolved from originally octaploid (= 8n) creatures[13]. This would explain why, for example, the Hox gene clusters occur four times per haploid genome of vertebrates, but only once in other animals.

The degree of ploidy of individual body cells of a multicellular cell can deviate from the degree of ploidy of the organism. The best-known example of this are certainly the polytene chromosomes of some insects (see also above). However, in addition to the predominant diploid cells, haploid, triploid and tetraploid cells have also been described in rare cases for the rat liver[14]. Tetraploidy results from the duplication of chromosomes without nuclear division, i.e. through endoreduplication or endomitosis. Haploid and triploid body cells have been found so rarely in diploid organisms that experimental errors or artifacts cannot be ruled out here. Their potential mechanism of formation is unclear. High degrees of ploidy are associated with correspondingly larger cell nuclei. Due to the larger amount of genetic material, very large body cells can also be supplied in this way.

Table: Number of chromosomes in normal body cells

Unless otherwise stated, the figures are based on [15].

Mammals
human46
chimpanzee48[16]
gorilla 48[17]
orangutan 48[17]
Rhesus monkey42[16]
Tarsier80
Bat (Myotis)44
House mouse40[16]
Golden hamster44
Rat (Rattus norvegicus)42[16]
dog78[15][16]
Pig (Sus scrofa)38[16]
Possum (Monodelphis domestica)18[16]
platypus52[18]
Echidna (both species) female / male 64/63[18]
other vertebrates
fishes 
Dogfish24
Goldfish94
Lamprey174
Amphibians 
Axolotl28
Midwife toad36
Reptiles 
alligator32
Slow worm44
Pond turtle50
Sand lizard38
Birds 
Domestic chicken78
blackbird80
Invertebrates
Horse roundworm (Ascaris megalocephala univalens)2[19]
Horse roundworm (Ascaris megalocephala bivalens)4[19]
Mosquito (Culex)6
Fruit fly (Drosophila melanogaster)8
Honeybee (Apis, female / male)32/16[20]
Sun animals44
Roman snail54
Octopus (sepia)12
Leeches (Glossosiphonia)26
Plants / mushrooms
mushroom 8
Sorrel female / male14 / 15
Einkorn / emmer / spelled14 / 28 / 42
Sweet cherry (depending on the variety)16, 24, 32, 54, 144
Cladophora (an alga)32
Coltsfoot60
Cyclamen48
bracken104
Worm fern164
Euglenaapprox. 200
Horsetail216
Adder tongue480

Karyogram

As Karyogram denotes a sorted representation of the chromosomes of a metaphase preparation. These preparations are made by adding an agent to cell cultures that prevents the formation of microtubules, e.g. B. colchicine or nocodazole. As a result, no spindle apparatus can develop and the cell cannot go into anaphase. As a result, a number of cells accumulate in the metaphase (see above) and the yield is increased accordingly. The cells are treated hypotonically, causing them to swell, fix and drop onto a slide, causing the metaphase chromosomes to lie next to each other (see first picture above). The chromosomes are stained, photographed and arranged according to size in the karyogram so that the karyotype can be determined (see figure on the right).

Karyograms are used both in the investigation of the karyotypes of organisms and in clinical application when chromosomal changes are suspected.

Chromosome mutations

Permanent changes to the chromosomes can occur when breaks occur in at least two places in the DNA double helix. In most cases, DNA double-strand breaks are correctly repaired so that permanent changes do not occur. However, if the wrong ends are joined together in a DNA repair of two different breaks, this leads to chromosome mutations. If the breakpoints are on the same chromosome, deletions (loss of a section) or inversions (flipping) can occur. Another type of mutation within a chromosome is duplication (duplication of a section). If the double-strand breaks are on different chromosomes, translocations can occur. These phenomena are described in more detail in their own articles, reviews are given in the articles Chromosome mutation and Chromosome aberration.

Chromosome mutations play a role in chromosome evolution as well as in the clinical field. In terms of clinical significance, hereditary diseases (see also below), tumor development (e.g. the Philadelphia chromosome) and radiation biology should be mentioned.

A distinction must be made between the structural changes mentioned in terms of numbers, i.e. an additional or a missing chromosome. These are not referred to as a chromosome mutation. Since only a single chromosome is affected, one speaks of trisomy (Not Triploidy) or monosomy (see chromosomal aberration).

Chromosome evolution

Chromosome evolution is the term used to describe the change in chromosomes in the course of evolution. Similar to external physical characteristics or the sequence of individual genes, the tribal history can also be traced on the chromosomes. For example, the chromosomes of humans (46 chromosomes) are very similar to those of the great apes (chimpanzees, gorillas and orangutans, each with 48 chromosomes). There are only two inter-chromosomal tags within this species group. Chromosome 2 is specifically human. The other species mentioned have two smaller chromosomes instead of this, which contain the corresponding gene sequences (see illustration). Gorilla-specific, on the other hand, is a translocation between those chromosomes that correspond to human chromosomes 5 and 17[17]. This results in the original karyotype of the group with 48 chromosomes, as it is still present in chimpanzees and orangutans today.

An evolutionarily stable change in the chromosomes is only possible if a chromosome mutation occurs in the germline. A “balanced” change, in which all chromosome segments are present in the correct number, initially has no disease value for the carrier. However, difficulties arise in meiosis. The change only occurs at first one Chromosome on (or on two in the case of fusions or translocations), but not on the respective homologous chromosomes. Since unlike otherwise identically structured partners, there is no normal meiotic mating. The risk of segregation errors and the resulting germ cells with redundant or missing chromosomal segments (and consequently sick children) increases sharply. In the vast majority of cases, such changes will therefore be lost again in subsequent generations. A stable situation can only be achieved if both Copies of the chromosomes involved carry the corresponding change. This could happen, for example, when using a dominant male one Change has numerous children, who in turn mate with each other, so that with the change, grandchildren arise on both copies of the chromosomes involved. These offspring have no selection disadvantage when they mate with one another. When mating with individuals with the original chromosomes, however, the resulting children again experience reduced fertility due to segregation errors. It is therefore assumed that “fixed” chromosome changes are a mechanism for speciation.

Species or groups of species that are more closely related do not always have to have more similar chromosomes than more distant species. For example, the chromosomes of great apes, including humans, are very similar to macaques (Macaca fuscata). However, the chromosomes of the closely related small great apes (gibbons) differ greatly from both those of the great apes and those of the macaques. Due to numerous modifications, only five of the gibbon chromosomes are (only) homologous to one human chromosome over their entire length[17]. Obviously, evolutionary changes in the karyotype proceed much faster in some groups (e.g. the gibbons) than in others (macaques, great apes). It is assumed that this is not due to a higher mutation rate, but to a more frequent fixation of changes that have occurred. One reason for this could be different lifestyles or social behavior. Gibbons live in small groups in which chromosome changes could prevail faster than in large herds. In Gibbons there are chromosomal polymorphisms (differences) in the karyotype of examined animals of the same species, which indicate that the rapid chromosome evolution continues in this group of animals. However, the relatively large number of polymorphisms also indicates that the selective disadvantage of mixed forms may be less than originally thought[17].

B chromosomes

B chromosomes[21],[22] are chromosomes that appear in addition to the normal karyotype in some species. By definition, they occur in these species only in a few individuals, often limited to certain populations and in different numbers. In some cases they are not found in all tissues. Through irregular behavior during mitosis and meiosis, you succeed in selfishly accumulating in the germline, so that a non-mendling inheritance takes place, in which the otherwise usual transfer rate of 50% for chromosomes is exceeded. Which mechanisms are responsible for this has only been clarified in a few cases (see [23] for an overview).

They are assigned to the parasitic or also egoistic genetic elements, which also include transposons. For easy differentiation, the normal chromosomes are referred to as A chromosomes in direct comparison. In many cases, B chromosomes probably originated from A chromosomes or parts thereof. They were first introduced in 1907 by E.B. Wilson described in Hemipteren without their parasitic properties first becoming apparent.

The evolution of the B chromosomes presumably largely depends on the interplay of the selection pressure on the host genome in favor of their elimination or shutdown on the one hand and their ability to evade this pressure on the other. Since the B chromosomes interact with the A chromosomes, where they occur they probably play an important role in genome evolution as a whole. Not all B chromosomes are harmful to the host. Some are neutral in their effect, for some even positive effects are discussed, e.g. B. with chives.

distribution

B chromosomes have so far been described in over 1300 plant species, 500 animal species and some fungi. All larger animal and plant groups are represented. Unsurprisingly, they were found particularly frequently in well-studied groups. In species with large genomes, Bs are more common than in those with small genomes (e.g. monocot versus dicotyledonous flowering plants, grasshoppers (Orthoptera) versus two-winged insects). In birds, which have comparatively small genomes, B chromosomes have only been found in a single species. The following list gives only a few examples.

Animals: B-chromosomes are widespread in the well-studied grasshoppers (e.g. Eyprepocnemis plorans, rarely more than three). Other insects with Bs are the wasp Nasonia and the fly Drosophila subsilvestris. Further examples: the flatworm P. nigra (rarely more than three); the New Zealand frog Leiopelma hochstetteri with up to 15 mitotically stable Bs; the fish Poecilia formosa. So far, Bs have been found in 55 (of 4629) mammals[24] z. B. in wood mice[25]. They have not been observed in humans and great apes.

Plants: Up to 34 B chromosomes have been described in maize plants, in chives (Allium schoenoprasum) up to 20. In wild plants, however, the maximum number found was three (Lolium perenne, B. dichromosomatica), presumably because they are subject to higher selection pressure. B chromosomes are widespread in lilies and related plants (Lilianae) and grasses (Poaceae), two groups that have been well studied.

Chromosomes in humans

Humans have 46 chromosomes, 2 of which are sex chromosomes or gonosomes (XX in women, XY in men, see above: sex determination). The chromosomes of the remaining 22 chromosome pairs are called autosomes. The autosomes were numbered from 1 to 22 according to their size in the microscopic preparation.

Properties of the sex chromosomes

Although the X and Y chromosomes differ greatly in size, they also have something in common. At both ends they contain regions in which the DNA sequence between the X and Y chromosomes is very similar, the pseudoautosomal regions (PAR). There are several genes in the PARs, which are duplicated in both sexes and which are also not subject to X inactivation (see above: dose compensation). Recombination between the X and Y chromosomes is possible in these regions during meiosis.

Even in non-recombining regions of the Y chromosome, around half of the genes have equivalents on the X chromosome. These are mainly genes of the basic metabolism. Two of the genes that are also found on the X chromosome are only active in the testicle. The other genes without a counterpart on the X chromosome are also only active in the testes, determine the male gender and control sperm production. Loss of a piece of the long arm near the centromere leads to short stature.

Genome and chromosome mutations of clinical significance

Chromosome aberrations, i.e. chromosome mutations (see also above) or an incorrect number of chromosomes (numerical chromosome aberration or genome mutation), can lead to clinical syndromes with sometimes serious symptoms.

An assignment of the clinical pictures to either chromosome mutations or numerical chromosome aberrations is not always possible. So z. B. Down syndrome in most cases is caused by an additional, complete chromosome 21 (free trisomy). However, around 3% of cases are due to translocations in which part of chromosome 21 is fused to another chromosome. Only this part is then present three times. The following syndromes are usually dealt with in detail in their own articles and are only presented here as an overview.

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Autosomal trisomies

Free trisomies in live births are only known for chromosomes 21, 18 and 13 in the autosomes. All three belong to the gene-poor chromosomes (compare the second figure in the section G, R and other chromosome bands above). From this it can be concluded that free trisomies of the other autosomes are incompatible with life.

  • Down syndrome or Trisomy 21 (triple / trisomal presence of genetic material of chromosome 21 in all or some body cells). Occurrence: 1 case in 600–800 newborns. Important symptoms include: Heart defects and mental retardation. While most of those affected previously died of infectious diseases in childhood, the average life expectancy today is over 60 years.
  • Edwards Syndrome or Trisomy 18 (triple / trisomal presence of genetic material of chromosome 18 in all or some body cells). Occurrence: 1 case in 2,500 newborns. Organ malformations are diverse, including Heart defects and kidney malformations. Severe intelligence defects (no language), adulthood is only reached in exceptional cases.
  • Patau syndrome or Trisomy 13 (triple / trisomal presence of genetic material of chromosome 13 in all or some body cells). Occurrence: 1 case in 6,000 newborns. Common symptoms includeHeart defects, cleft lip, jaw and palate, polydactyly (multiple fingers) and severe intelligence defects. Adulthood is only reached in exceptional cases.
  • Trisomy 8 (triple / trisomal presence of genetic material of chromosome 8 in some body cells). Common symptoms include deep hand and foot lines, vertebral malformations, neural tube malformations (often spina bifida aperta) and tall stature.

Variations in the number of sex chromosomes

  • Ullrich-Turner syndrome, (45, X). Missing second sex chromosome. Occurrence: 1 case in 3,000 newborns. Women with this syndrome have underdeveloped female sexual characteristics, short stature, deep hairline, unusual eye and bone development, a funnel-shaped chest, and are mostly sterile. The intelligence is normal, sometimes spatial imagination or math skills are below average.
  • Trisomy X, (47, XXX). Trisomy X is the clinically most normal chromosomal aberration. Presumably, many cases are never discovered. Intelligence is usually lower than that of siblings. Fertility can be slightly reduced. The offspring show hardly any increased rate of chromosome aberrations.
  • 48, XXXX and 49, XXXXX. As the number of X chromosomes increases, intelligence and fertility decrease.
  • Klinefelter syndrome, (almost always 47, XXY; rarely 48, XXXY or 49, XXXXY). 1 case in 1,000 male newborns. Men with this syndrome are often sterile, tall, with unusually long arms and legs, a tendency to develop breasts (pseudo-gynecomastia), and reduced body hair. The intelligence quotient is on average 10 lower than that of siblings.
  • XYY syndrome (47, XYY). Men with this syndrome are usually phenotypically normal and diagnosed by chance. Life expectancy is not restricted, fertility is almost normal, they are on average 10 cm taller than their brothers and their intelligence is slightly reduced compared to siblings. Occasionally, disorders associated with chromosome aberration such as undescended testicles can occur.
  • Higher grade Y polysomies: 48, XXYY men are similar to XYY men, but sterile and with a tendency to be less intelligent. The latter increases in 48, XYYY and the very rare 49, XYYYY men. Organ malformations also occur.

Marker chromosomes

Marker chromosomes are all chromosomes that are not readily definable and that appear in addition to normal chromosomes. They consist of material from the normal chromosomes, but are usually small so that they cannot be identified by G-banding (see above). This can be achieved with high-resolution fluorescence in situ hybridization. A clinically important group are so-called “small surplus marker chromosomes”. They cause a diverse group of syndromes, often associated with intellectual disabilities. At around 30%, marker chromosomes made from material from chromosome 15 are the most common. Isochromosomes of the short arm of chromosome 12, the Pallister-Killian syndrome, follow with 11%. Cat eye syndrome is another example. The karyotype is given as 47, XY, + mar or 47, XX, + mar.

Deletions on autosomes

Autosome monosomies do not occur. The associated damage is apparently incompatible with life. However, there are a large number of different deletions of parts of an autosome, some of which are only known from a few clinical cases. The following list is therefore not exhaustive and only includes the most popular examples.

  • Although not long known, deletion of the end of the short arm of chromosome 1 is probably the most common deletion (1 case in 5,000-10,000 newborns). The symptoms are not uniform, and most of the time there is severe intellectual disability.
  • Cri du chat syndrome is caused by deletion of the end of the short arm of chromosome 5. It was described as the first autosomal deletion in 1963. The frequency is around one case in 50,000 newborns. In early childhood, children stand out for their high-pitched screaming, which is reminiscent of the screaming of cats and which is caused by misjudgments of the larynx. They have widely spaced eyes (hypertelorism), a small head (microcephaly) and jaws, and their intelligence is reduced. Since internal organs are usually not affected, the chances of survival are comparatively good.
  • Wolf-Hirschhorn syndrome is caused by deletion of the end of the short arm of chromosome 4. The frequency is also around one case in 50,000 newborns. Affected people are usually severely impaired cognitively and have stunted growth. Less than half of the children survive the first 18 months.
  • De Grouchy syndrome comes in two variants, which are caused by deletions of the different arms of chromosome 18.

Further examples are the Williams-Beuren syndrome (7q11.23) and the Smith-Magenis syndrome (17p11.2 - frequency between 1: 15,000 to 1: 25,000 births given).

Deletions of the region 15q11.2-q12 are a specialty. This region is subject to an epigenetic regulation, the "imprinting": Depending on whether this region was inherited from the father or the mother, certain genes are active or inactive. Usually both cases exist once. However, if one of the two is missing, e.g. B. by deletion, the clinical pictures differ depending on whether a region inherited from the mother (Angelman syndrome) or a region inherited from the father (Prader-Willi syndrome) is missing.

The ICD-10 code O35.1 is given when caring for an expectant mother in the event of (suspected) chromosomal peculiarities in the unborn child.

literature

  • Gholamali Tariverdian: Chromosomes, genes, mutations - human genetic consultation hours. Springer, Berlin 1995, ISBN 3540586679
  • Walther Traut: Chromosomes. Springer, Berlin 1991, ISBN 3540533192
  • Jan Murken, Tiemo Grimm, Elke Holinski-Feder. Pocket textbook human genetics, 7th edition, Thieme, Stuttgart, 2006, ISBN 3-13-139297-5.
  • About history: T. Cremer: From cell theory to chromosome theory, Springer Verlag Berlin Heidelberg New York Tokyo, 1985, ISBN 3-540-13987-7. Online version here.
  • Chromosomes; Chromosome Theory (Part II)
  • Chromosome structures and structural changes in the chromosomes
  • Fine structure of the chromosomes
  • Thumbnail overview chromosomes

References

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Category: nucleic acid