A chromosome and itspackaged long strand of DNA unraveled. The DNA'sbase pairs encode genes, which provide functions. A human DNA can have up to 500 million base pairs with thousands of genes.
Condensed chromosome (purple rod) inside a bone marrow erythrokaryocyte undergoing mitosis
Normally, chromosomes are visible under alight microscope only during themetaphase ofcell division, where all chromosomes are aligned in the center of the cell in their condensed form.[4] Before this stage occurs, each chromosome is duplicated (S phase), and the two copies are joined by acentromere—resulting in either an X-shaped structure if the centromere is located equatorially, or a two-armed structure if the centromere is located distally; the joined copies are called 'sister chromatids'. Duringmetaphase, the duplicated structure (called a 'metaphase chromosome') is highly condensed and thus easiest to distinguish and study.[5] In animal cells, chromosomes reach their highest compaction level inanaphase duringchromosome segregation.[6]
The term 'chromosome' is sometimes used in a wider sense to refer to the individualized portions ofchromatin in cells, which may or may not be visible under light microscopy. In a narrower sense, 'chromosome' can be used to refer to the individualized portions of chromatin during cell division, which are visible under light microscopy due to high condensation.
Some of the earlykaryological terms have become outdated.[11][12] For example, 'chromatin' (Flemming 1880) and 'chromosom' (Waldeyer 1888) both ascribe color to a non-colored state.[13]
Walter Sutton (left) andTheodor Boveri (right) independently developed the chromosome theory of inheritance in 1902.
Otto Bütschli was the first scientist to recognize the structures now known as chromosomes.[14]
In a series of experiments beginning in the mid-1880s,Theodor Boveri gave definitive contributions to elucidating that chromosomes are thevectors ofheredity, with two notions that became known as 'chromosome continuity' and 'chromosome individuality'.[15]
Wilhelm Roux suggested that every chromosome carries a differentgenetic configuration, and Boveri was able to test and confirm this hypothesis. Aided by the rediscovery at the start of the 1900s ofGregor Mendel's earlier experimental work, Boveri identified the connection between the rules of inheritance and the behaviour of the chromosomes. Two generations of Americancytologists were influenced by Boveri:Edmund Beecher Wilson,Nettie Stevens,Walter Sutton andTheophilus Painter (Wilson, Stevens, and Painter actually worked with him).[16]
In his famous textbook,The Cell in Development and Heredity, Wilson linked together the independent work of Boveri and Sutton (both around 1902) by naming the chromosome theory of inheritance the 'Boveri–Sutton chromosome theory' (sometimes known as the 'Sutton–Boveri chromosome theory').[17]Ernst Mayr remarks that the theory was hotly contested by some famous geneticists, includingWilliam Bateson,Wilhelm Johannsen,Richard Goldschmidt andT.H. Morgan, all of a rather dogmatic mindset. Eventually, absolute proof came from chromosome maps in Morgan's own laboratory.[18]
The number of human chromosomes was published by Painter in 1923. By inspection through a microscope, he counted 24 pairs of chromosomes, giving 48 in total. His error was copied by others, and it was not until 1956 that the true number (46) was determined by Indonesian-borncytogeneticistJoe Hin Tjio.[19]
Some bacteria have more than one chromosome. For instance,Spirochaetes such asBorrelia burgdorferi (causingLyme disease), contain a singlelinear chromosome.[24]Vibrios typically carry two chromosomes of very different size. Genomes of the genusBurkholderia carry one, two, or three chromosomes.[25]
Prokaryotic chromosomes have less sequence-based structure than eukaryotes. Bacteria typically have a one-point (theorigin of replication) from which replication starts, whereas some archaea contain multiple replication origins.[26] The genes in prokaryotes are often organized inoperons and do not usually containintrons, unlike eukaryotes.
Prokaryotes do not possess nuclei. Instead, their DNA is organized into a structure called thenucleoid.[27][28] The nucleoid is a distinct structure and occupies a defined region of the bacterial cell. This structure is, however, dynamic and is maintained and remodeled by the actions of a range of histone-like proteins, which associate with the bacterial chromosome.[29] Inarchaea, the DNA in chromosomes is even more organized, with the DNA packaged within structures similar to eukaryotic nucleosomes.[30][31]
Certain bacteria also containplasmids or otherextrachromosomal DNA. These are circular structures in thecytoplasm that contain cellular DNA and play a role inhorizontal gene transfer.[5] In prokaryotes and viruses,[32] the DNA is often densely packed and organized; in the case of archaea, by homology to eukaryotic histones, and in the case of bacteria, byhistone-like proteins.
Bacterial chromosomes tend to be tethered to theplasma membrane of the bacteria. In molecular biology application, this allows for its isolation from plasmid DNA by centrifugation of lysed bacteria and pelleting of the membranes (and the attached DNA).
Prokaryotic chromosomes and plasmids are, like eukaryotic DNA, generallysupercoiled. The DNA must first be released into its relaxed state for access fortranscription, regulation, andreplication.
Each eukaryotic chromosome consists of a long linearDNA molecule associated withproteins, forming a compact complex of proteins and DNA calledchromatin. Chromatin contains the vast majority of the DNA in an organism, but asmall amount inherited maternally can be found in themitochondria. It is present in mostcells, with a few exceptions, for example,red blood cells.
Histones are responsible for the first and most basic unit of chromosome organization, thenucleosome.
Eukaryotes (cells with nuclei such as those found in plants, fungi, and animals) possess multiple large linear chromosomes contained in the cell's nucleus. Each chromosome has onecentromere, with one or two arms projecting from the centromere, although, under most circumstances, these arms are not visible as such. In addition, most eukaryotes have a small circularmitochondrial genome, and some eukaryotes may have additional small circular or linearcytoplasmic chromosomes.
The major structures in DNA compaction:DNA, thenucleosome, the 10 nm "beads-on-a-string" fibre, the 30 nm fibre and themetaphase chromosome
In the nuclear chromosomes of eukaryotes, the uncondensed DNA exists in a semi-ordered structure, where it is wrapped aroundhistones (structural proteins), forming a composite material called chromatin.
The packaging of DNA into nucleosomes causes a 10 nanometer fibre which may further condense up to 30 nm fibres.[33] Most of the euchromatin in interphase nuclei appears to be in the form of 30-nm fibers.[33] Chromatin structure is the more decondensed state, i.e. the 10-nm conformation allows transcription.[33]
Heterochromatin vs. euchromatin
Duringinterphase (the period of thecell cycle where the cell is not dividing), two types of chromatin can be distinguished:
Euchromatin, which consists of DNA that is active, e.g., being expressed as protein.
Heterochromatin, which consists of mostly inactive DNA. It seems to serve structural purposes during the chromosomal stages. Heterochromatin can be further distinguished into two types:
Constitutive heterochromatin, which is never expressed. It is located around the centromere and usually containsrepetitive sequences.
Facultative heterochromatin, which is sometimes expressed.
Human chromosomes duringmetaphaseStages of early mitosis in a vertebrate cell with micrographs of chromatids
In the early stages ofmitosis ormeiosis (cell division), the chromatin double helix becomes more and more condensed. They cease to function as accessible genetic material (transcription stops) and become a compact transportable form. The loops of thirty-nanometer chromatin fibers are thought to fold upon themselves further to form the compact metaphase chromosomes of mitotic cells. The DNA is thus condensed about ten-thousand-fold.[33]
Thechromosome scaffold, which is made of proteins such ascondensin,TOP2A andKIF4,[34] plays an important role in holding the chromatin into compact chromosomes. Loops of thirty-nanometer structure further condense with scaffold into higher order structures.[35]
This highly compact form makes the individual chromosomes visible, and they form the classic four-arm structure, a pair of sisterchromatids attached to each other at thecentromere. The shorter arms are calledp arms (from the Frenchpetit, small) and the longer arms are calledq arms (q followsp in the Latin alphabet; q-g "grande"; alternatively it is sometimes said q is short forqueue meaning tail in French[36]). This is the only natural context in which individual chromosomes are visible with an opticalmicroscope.
Mitotic metaphase chromosomes are best described by a linearly organized longitudinally compressed array of consecutive chromatin loops.[37]
During mitosis,microtubules grow from centrosomes located at opposite ends of the cell and also attach to the centromere at specialized structures calledkinetochores, one of which is present on each sisterchromatid. A special DNA base sequence in the region of the kinetochores provides, along with special proteins, longer-lasting attachment in this region. The microtubules then pull the chromatids apart toward the centrosomes, so that each daughter cell inherits one set of chromatids. Once the cells have divided, the chromatids are uncoiled and DNA can again be transcribed. In spite of their appearance, chromosomes are structurally highly condensed, which enables these giant DNA structures to be contained within a cell nucleus.
Chromosomes in humans can be divided into two types:autosomes (body chromosome(s)) and allosome (sex chromosome(s)). Certain genetic traits are linked to a person's sex and are passed on through the sex chromosomes. The autosomes contain the rest of the genetic hereditary information. All act in the same way during cell division. Human cells have 23 pairs of chromosomes (22 pairs of autosomes and one pair of sex chromosomes), giving a total of 46 per cell. In addition to these, human cells have many hundreds of copies of themitochondrial genome.Sequencing of thehuman genome has provided a great deal of information about each of the chromosomes. Below is a table compiling statistics for the chromosomes, based on theSanger Institute's human genome information in theVertebrate Genome Annotation (VEGA) database.[38] Number of genes is an estimate, as it is in part based ongene predictions. Total chromosome length is an estimate as well, based on the estimated size of unsequencedheterochromatin regions.
Based on the micrographic characteristics of size, position of thecentromere and sometimes the presence of achromosomal satellite, the human chromosomes are classified into the following groups:[41][42]
Although thereplication andtranscription ofDNA is highly standardized in eukaryotes, the same cannot be said for their karyotypes, which are often highly variable. There may be variation between species in chromosome number and in detailed organization.In some cases, there is significant variation within species. Often there is:
1. variation between the two sexes
2. variation between thegermline andsoma (betweengametes and the rest of the body)
Also, variation in karyotype may occur during development from the fertilized egg.
The technique of determining the karyotype is usually calledkaryotyping. Cells can be locked part-way through division (in metaphase)in vitro (in a reaction vial) withcolchicine. These cells are then stained, photographed, and arranged into akaryogram, with the set of chromosomes arranged, autosomes in order of length, and sex chromosomes (here X/Y) at the end.
Like many sexually reproducing species, humans have specialgonosomes (sex chromosomes, in contrast toautosomes). These are XX in females and XY in males.
Investigation into the human karyotype took many years to settle the most basic question:How many chromosomes does a normaldiploid human cell contain? In 1912,Hans von Winiwarter reported 47 chromosomes inspermatogonia and 48 inoogonia, concluding anXX/XOsex determination mechanism.[44] In 1922,Painter was not certain whether the diploid number of man is 46 or 48, at first favouring 46.[45] He revised his opinion later from 46 to 48, and he correctly insisted on humans having anXX/XY system.[46]
New techniques were needed to definitively solve the problem:
Pretreating cells in ahypotonic solution0.075 M KCl, which swells them and spreads the chromosomes
Squashing the preparation on the slide forcing the chromosomes into a single plane
Cutting up a photomicrograph and arranging the result into an indisputable karyogram.
It took until 1954 before the human diploid number was confirmed as 46.[47][48] Considering the techniques of Winiwarter and Painter, their results were quite remarkable.[49]Chimpanzees, the closest living relatives to modern humans, have 48 chromosomes as do the othergreat apes: in humans two chromosomes fused to formchromosome 2.
In Down syndrome, there are three copies of chromosome 21.
Chromosomal aberrations are disruptions in the normal chromosomal content of a cell. They can cause genetic conditions in humans, such asDown syndrome,[50] although most aberrations have little to no effect. Some chromosome abnormalities do not cause disease in carriers, such astranslocations, orchromosomal inversions, although they may lead to a higher chance of bearing a child with a chromosome disorder.[citation needed] Abnormal numbers of chromosomes or chromosome sets, calledaneuploidy, may be lethal or may give rise to genetic disorders.[51]Genetic counseling is offered for families that may carry a chromosome rearrangement.
The gain or loss of DNA from chromosomes can lead to a variety ofgenetic disorders.[52] Human examples include:
Cri du chat, caused by thedeletion of part of the short arm of chromosome 5. "Cri du chat" means "cry of the cat" in French; the condition was so-named because affected babies make high-pitched cries that sound like those of a cat. Affected individuals have wide-set eyes, a small head and jaw, moderate to severe mental health problems, and are very short.
DiGeorge syndrome, also known as 22q11.2 deletion syndrome. Symptoms are mild learning disabilities in children, with adults having an increased risk ofschizophrenia. Infections are also common in children because of problems with the immune system's T cell-mediated response due to an absence of hypoplastic thymus.[53]
Down syndrome, the most common trisomy, usually caused by an extra copy of chromosome 21 (trisomy 21). Characteristics include decreased muscle tone, stockier build, asymmetrical skull, slanting eyes, and mild to moderate developmental disability.[54]
Edwards syndrome, or trisomy-18, the second most common trisomy.[55] Symptoms include motor retardation, developmental disability, and numerous congenital anomalies causing serious health problems. Ninety percent of those affected die in infancy. They have characteristic clenched hands and overlapping fingers.
Isodicentric 15, also called idic(15), partial tetrasomy 15q, or inverted duplication 15 (inv dup 15).
Jacobsen syndrome, which is very rare. It is also called the 11q terminal deletion disorder.[56] Those affected have normal intelligence or mild developmental disability, with poor expressive language skills. Most have a bleeding disorder calledParis-Trousseau syndrome.
Klinefelter syndrome (XXY). Men with Klinefelter syndrome are usually sterile, and tend to be taller than their peers, with longer arms and legs. Boys with the syndrome are often shy and quiet, and have a higher incidence ofspeech delay anddyslexia. Without testosterone treatment, some may developgynecomastia during puberty.
Patau Syndrome, also called D-Syndrome or trisomy-13. Symptoms are somewhat similar to those of trisomy-18, without the characteristic folded hand.
Triple-X syndrome (XXX). XXX girls tend to be tall and thin, and have a higher incidence of dyslexia.
Turner syndrome (X instead of XX or XY). In Turner syndrome, female sexual characteristics are present but underdeveloped. Females with Turner syndrome often have a short stature, low hairline, abnormal eye features and bone development, and a "caved-in" appearance to the chest.
Wolf–Hirschhorn syndrome, caused by partial deletion of the short arm of chromosome 4. It is characterized by growth retardation, delayed motor skills development, "Greek Helmet" facial features, and mild to profound mental health problems.
XYY syndrome. XYY boys are usually taller than their siblings. Like XXY boys and XXX girls, they are more likely to have learning difficulties.
Exposure of males to certain lifestyle, environmental and/or occupational hazards may increase the risk of aneuploid spermatozoa.[57] In particular, risk of aneuploidy is increased by tobacco smoking,[58][59] and occupational exposure to benzene,[60] insecticides,[61][62] and perfluorinated compounds.[63] Increased aneuploidy is often associated with increased DNA damage in spermatozoa.
The number of chromosomes ineukaryotes is highly variable. It is possible for chromosomes to fuse or break and thus evolve into novel karyotypes. Chromosomes can also be fused artificially. For example, when the 16 chromosomes ofyeast were fused into one giant chromosome, it was found that the cells were still viable with only somewhat reduced growth rates.[64]
The tables below give the total number of chromosomes (including sex chromosomes) in a cell nucleus for various eukaryotes. Most arediploid, such ashumans who have 22 different types ofautosomes—each present as two homologous pairs—and twosex chromosomes, giving 46 chromosomes in total. Some other organisms have more than two copies of their chromosome types, for examplebread wheat which ishexaploid, having six copies of seven different chromosome types for a total of 42 chromosomes.
Normal members of a particular eukaryotic species all have the same number of nuclear chromosomes. Other eukaryotic chromosomes, i.e., mitochondrial and plasmid-like small chromosomes, are much more variable in number, and there may be thousands of copies per cell.
Asexually reproducing species have one set of chromosomes that are the same in all body cells. However, asexual species can be either haploid or diploid.
Sexually reproducing species havesomatic cells (body cells) that arediploid [2n], having two sets of chromosomes (23 pairs in humans), one set from the mother and one from the father.Gametes (reproductive cells) arehaploid [n], having one set of chromosomes. Gametes are produced bymeiosis of a diploidgermline cell, during which the matching chromosomes of father and mother can exchange small parts of themselves (crossover) and thus create new chromosomes that are not inherited solely from either parent. When a male and a female gamete merge duringfertilization, a new diploid organism is formed.
Some animal and plant species arepolyploid [Xn], having more than two sets ofhomologous chromosomes. Important crops such as tobacco or wheat are often polyploid, compared to their ancestral species. Wheat has a haploid number of seven chromosomes, still seen in somecultivars as well as the wild progenitors. The more common types of pasta and bread wheat are polyploid, having 28 (tetraploid) and 42 (hexaploid) chromosomes, compared to the 14 (diploid) chromosomes in wild wheat.[90]
Prokaryote species generally have one copy of each major chromosome, but most cells can easily survive with multiple copies.[91] For example,Buchnera, asymbiont ofaphids has multiple copies of its chromosome, ranging from 10 to 400 copies per cell.[92] However, in some large bacteria, such asEpulopiscium fishelsoni up to 100,000 copies of the chromosome can be present.[93] Plasmids and plasmid-like small chromosomes are, as in eukaryotes, highly variable in copy number. The number of plasmids in the cell is almost entirely determined by the rate of division of the plasmid – fast division causes high copy number.
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