Information about Sex Chromosomes

For information about chromosomes in genetic algorithms, see chromosome (genetic algorithm).

A chromosome is a single large macromolecule of DNA, and constitutes a physically organized form of DNA in a cell. It is a very long, continuous piece of DNA (a single DNA molecule), which contains many genes, regulatory elements and other intervening nucleotide sequences. A broader definition of "chromosome" also includes the DNA-bound proteins which serve to package and manage the DNA. The word chromosome comes from the Greek χρῶμα (chroma, color) and σῶμα (soma, body) due to its capacity to be stained very strongly with vital and supravital dyes.

Chromosomes vary extensively between different organisms. The DNA molecule may be circular or linear, and can contain anything from tens of kilobase pairs to hundreds of megabase pairs. Typically eukaryotic cells (cells with nuclei) have large linear chromosomes and prokaryotic cells (cells without nuclei) smaller circular chromosomes, although there are many exceptions to this rule. Furthermore, cells may contain more than one type of chromosome; for example mitochondria in most eukaryotes and chloroplasts in plants have their own small chromosome in addition to the nuclear chromosomes.

In eukaryotes nuclear chromosomes are packaged by proteins (particularly histones) into chromatin to fit the massive molecules into the nucleus. The structure of chromatin varies through the cell cycle, and is responsible for the compaction of DNA into the classic four-arm structure during mitosis and meiosis. Prokaryotes do not form chromatin, because the cells lack proteins required and the circular configuration of the molecule prevents this.

"Chromosome" is a rather loosely defined term. In prokaryotes, a small circular DNA molecule may be called either a plasmid or a small chromosome. In viruses, mitochondria, and chloroplasts their DNA molecules are commonly referred to as chromosomes, despite being naked molecules, as they constitute the complete genome of the organism or organelle.

History

Chromosomes were first observed in plant cells by a Swiss botanist named Karl Wilhelm von Nägeli in 1842, and independently in Ascaris worms by Belgian scientist Edouard Van Beneden (1846-1910). The use of basophilic aniline dyes was a fundamentally new technique for effectively staining the chromatin material in the nucleus. Their behavior in animal (salamander) cells was later described in detail by German cytologist and professor of anatomy Walther Flemming, the discoverer of mitosis, in 1882. The name was invented later by another German anatomist, Heinrich von Waldeyer in 1888.

Chromosomes in eukaryotes

Eukaryotes (cells with nuclei such as plants, yeast, and animals) possess multiple large linear chromosomes contained in the cell's nucleus. Each chromosome has one centromere, 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 circular mitochondrial genome, and some eukaryotes may have additional small circular or linear cytoplasmic chromosomes.

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

Chromatin

Main article: Chromatin

Chromatin is the complex of DNA and protein found in the eukaryotic nucleus which packages chromosomes. The structure of chromatin varies significantly between different stages of the cell cycle, according to the requirements of the DNA.

Interphase chromatin

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

• Euchromatin, which consists of DNA that is active, e.g., 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 contains repetitive sequences.
• Facultative heterochromatin, which is sometimes expressed.

Individual chromosomes cannot be distinguished at this stage - they appear in the nucleus as a homogeneous tangled mix of DNA and protein.

Metaphase chromatin and division

In the early stages of mitosis or meiosis (cell division), the chromatin strands become more and more condensed. They cease to function as accessible genetic material (transcription stops) and become a compact transportable form. This compact form makes the individual chromosomes visible, and they form the classic four arm structure, a pair of sister chromatids attached to each other at the centromere. The shorter arms are called p arms (from the French petit, small) and the longer arms are called q arms (q follows p in the Latin alphabet). This is the only natural context in which individual chromosomes are visible with an optical microscope.

During divisions long microtubules attach to the centromere and the two opposite ends of the cell. The microtubules then pull the chromatids apart, so that each daughter cell inherits one set of chromatids. Once the cells have divided, the chromatids are uncoiled and can function again as chromatin. In spite of their appearance, chromosomes are structurally highly condensed which enables these giant DNA structures to be contained within a cell nucleus (Fig. 2).

The self assembled microtubules form the spindle, which attaches to chromosomes at specialized structures called kinetochores, one of which is present on each sister chromatid. A special DNA base sequence in the region of the kinetochores provides, along with special proteins, longer-lasting attachment in this region.

Chromosomes in prokaryotes

Prokaryotes (eg. Bacteria) typically have a single circular chromosome, but many variations do exist. Bacterial DNA also exists as plasmids, essentially miniature chromosomes, which are small circular pieces of DNA that are readily transmitted between bacteria. The distinction between plasmids and chromosomes is poorly defined, though size and necessity are generally taken into account.

Structure in sequences

Prokaryotes chromosomes have less sequence-based structure than eukaryotes. They do, however, typically have a single point, the origin of replication, from which replication starts.

The genes in prokaryotes are often organised in operons, and do not contain introns, unlike eukaryotes.

Location in the cell

Bacterial chromosomes tend to be tethered to the plasma 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).

DNA packaging

Prokaryotes do not possess histones or nuclei, and so do not possess chromatin like eukaryotes. There is, however, thought to be some structural organisation to help condense the large molecule into the small prokaryotic cell.

Prokaryotic chromosomes and plasmids are, like eukaryotic DNA, generally supercoiled. The DNA must first be released into its relaxed state for access for transcription, regulation, and replication.

Number of chromosomes in various organisms

Eukaryotes

Chromosome numbers (2n) in some plants Plant Species # Arabidopsis thaliana 10 Rye 14 Maize 20 Einkorn wheat[1] 14 Durum wheat[1] 28 Bread wheat[1] 42 Wild tobacco 24 Cultivated tobacco 48 Adder's Tongue Fern[2] 1262	Chromosome numbers (2n) in some animals Species # Species # Common fruit fly 8 Guinea Pig 16 Dove 16 Snail 24 Earthworm[3] 36 Tibetan fox 36 Domestic cat 38 Domestic pig 38 Lab mouse 40 Lab rat 42 Rabbit 44 Syrian hamster 44 Hare 46 Human[3] 46 Gorillas, chimpanzees[3] 48 Domestic sheep 54 Elephants[5] 56 Cow 60 Donkey 62 Horse 64 Dog[6] 78 Chicken[7] 39 Goldfish[8] 100-104 Silkworm[9] 28
Chromosome numbers in other organisms Species Large Chromosomes Intermediate Chromosomes Small Chromosomes Trypanosoma brucei 11 6 ~100

Normal members of a particular eukaryotic species all have the same number of nuclear chromosomes (see the table). 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, which is the same in all body cells.

Sexually reproducing species have somatic cells (body cells), which are diploid [2n] having two sets of chromosomes, one from the mother and one from the father. Gametes, reproductive cells, are haploid [n]: they have one set of chromosomes. Gametes are produced by meiosis of a diploid germ line cell. During meiosis, 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 (fertilization), a new diploid organism is formed.

Some animal and plant species are polyploid [Xn]: they have more than two sets of homologous chromosomes. Agriculturally important plants such as tobacco or wheat are often polyploid compared to their ancestral species. Wheat has a haploid number of seven chromosomes, still seen in some cultivars as well as the wild progenitors. The more common pasta and bread wheats are polyploid, having 28 (tetraploid) and 42 (hexaploid) chromosomes compared to the 14 (diploid) chromosomes in the wild wheat.^[10]

Historical note: In 1921, Theophilus Painter claimed, based on his observations, that human sex cells had 24 chromosomes each, giving humans 48 chromosomes total. It wasn't until 1955 that the number of chromosomes was clearly shown to be 23.

Prokaryotes

Prokaryote species generally have one copy of each major chromosome, but most cells can easily survive with multiple copies. Plasmids and plasmid-like small chromosomes are, like in eukaryotes, very 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, and vice versa.

Karyotype

Main article: Karyotype

Karyotyping is a technique used to determine the (diploid) number of nuclear chromosomes of a eukaryotic organism, and may be used for determining sex and spotting chromosomal abnormalities. Cells can be locked part way through division (in metaphase) in vitro (in a reaction vial) with colchicine. These cells are then stained, photographed and arranged into a karyotype (an ordered set of chromosomes, Fig. 3), also called karyogram.

Like many sexually reproducing species, humans have special gonosomes (sex chromosomes, in contrast to autosomes). These are XX in females and XY in males, and can be seen in the karyotype, Fig. 3.

Chromosomal aberrations

Main articles: Chromosome abnormalities and aneuploidy

Chromosomal aberrations are disruptions in the normal chromosomal content of a cell, and are a major cause of genetic conditions in humans, such as Down syndrome. Some chromosome abnormalities do not cause disease in carriers, such as translocations, or chromosomal inversions, although they may lead to a higher chance of having a child with a chromosome disorder. Abnormal numbers of chromosomes or chromosome sets, aneuploidy, may be lethal or give rise to genetic disorders. Genetic counseling is offered for families that may carry a chromosome rearrangement.

The gain or loss of chromosome material can lead to a variety of genetic disorders. Human examples include:

• Cri du chat, which is caused by the deletion of part of the short arm of chromosome 5. "Cri du chat" means "cry of the cat" in French, and the condition was so-named because affected babies make high-pitched cries that sound like a cat. Affected individuals have wide-set eyes, a small head and jaw and are moderately to severely mentally retarded and very short.
• Wolf-Hirschhorn syndrome, which is caused by partial deletion of the short arm of chromosome 4. It is characterized by severe growth retardation and severe to profound mental retardation.
• Down's syndrome, usually is caused by an extra copy of chromosome 21 (trisomy 21). Characteristics include decreased muscle tone, asymmetrical skull, slanting eyes and mild to moderate mental retardation.
• Edwards syndrome, which is the second most common trisomy after Down syndrome. It is a trisomy of chromosome 18. Symptoms include mental and motor retardation and numerous congenital anomalies causing serious health problems. Ninety percent die in infancy; however, those who live past their first birthday usually are quite healthy thereafter. They have a characteristic hand appearance with clenched hands and overlapping fingers.
• Patau Syndrome, also called D-Syndrome or trisomy-13. Symptoms are somewhat similar to those of trisomy-18, but they do not have the characteristic hand shape.
• Idic15, abbreviation for Isodicentric 15 on chromosome 15; also called the following names due to various researches, but they all mean the same; IDIC(15), Inverted dupliction 15, extra Marker, Inv dup 15, partial tetrasomy 15
• Jacobsen syndrome, also called the terminal 11q deletion disorder.http://www.11q.org This is a very rare disorder. Those affected have normal intelligence or mild mental retardation, with poor expressive language skills. Most have a bleeding disorder called Paris-Trousseau syndrome.
• Klinefelter's syndrome (XXY). Men with Klinefelter syndrome are usually sterile, and tend to have longer arms and legs and to be taller than their peers. Boys with the syndrome are often shy and quiet, and have a higher incidence of speech delay and dyslexia. During puberty, without testosterone treatment, some of them may develop gynecomastia.
• Turner syndrome (X instead of XX or XY). In Turner syndrome, female sexual characteristics are present but underdeveloped. People with Turner syndrome often have a short stature, low hairline, abnormal eye features and bone development and a "caved-in" appearance to the chest.
• XYY syndrome. XYY boys are usually taller than their siblings. Like XXY boys and XXX girls, they are somewhat more likely to have learning difficulties.
• Triple-X syndrome (XXX). XXX girls tend to be tall and thin. They have a higher incidence of dyslexia.
• Small supernumerary marker chromosome. This means there is an extra, abnormal chromosome. Features depend on the origin of the extra genetic material. Cat-eye syndrome and isodicentric chromosome 15 syndrome (or Idic15) are both caused by a supernumerary marker chromosome, as is Pallister-Killian syndrome.

Chromosomal mutations produce changes in whole chromosomes (more than one gene) or in the number of chromosomes present.

• Deletion- loss of part of a chromosome
• Duplication- extra copies of a part of a chromosome
• Inversion- reverse the direction of a part of a chromosome
• Translocation- part of a chromosome breaks off and attaches to another chromosome

Most mutations are neutral- have little or no effect

A detailed graphical display of all human chromosomes and the diseases annotated at the correct spot may be found at [1].

Human chromosomes

Human cells have 23 pairs of large linear nuclear chromosomes, giving a total of 46 per cell. In addition to these, human cells have many hundreds of copies of the mitochondrial genome. Sequencing of the human genome has provided a great deal of information about each of the chromosomes. Below is a table compiling statistics for the chromosomes, based on the Sanger Institute's human genome information in the Vertebrate Genome Annotation (VEGA) database.^[11] Number of genes is an estimate as it is in part based on gene predictions. Total chromosome length is an estimate as well, based on the estimated size of unsequenced heterochromatin regions.

Chromosome	Genes	Total bases	Sequenced bases[12]
1	3,148	247,200,000	224,999,719
2	902	242,750,000	237,712,649
3	1,436	199,450,000	194,704,827
4	453	191,260,000	187,297,063
5	609	180,840,000	177,702,766
6	1,585	170,900,000	167,273,992
7	1,824	158,820,000	154,952,424
8	781	146,270,000	142,612,826
9	1,229	140,440,000	120,312,298
10	1,312	135,370,000	131,624,737
11	405	134,450,000	131,130,853
12	1,330	132,290,000	130,303,534
13	623	114,130,000	95,559,980
14	886	106,360,000	88,290,585
15	676	100,340,000	81,341,915
16	898	88,820,000	78,884,754
17	1,367	78,650,000	77,800,220
18	365	76,120,000	74,656,155
19	1,553	63,810,000	55,785,651
20	816	62,440,000	59,505,254
21	446	46,940,000	34,171,998
22	595	49,530,000	34,893,953
X (sex chromosome)	1,093	154,910,000	151,058,754
Y (sex chromosome)	125	57,740,000	22,429,293

See also

• Locus (explains gene location nomenclature)
• Sex-determination system
• XY sex-determination system
• X chromosome
• X-inactivation
• Y chromosome
• Y-chromosomal Adam
• Y-chromosomal Aaron
• Genetic genealogy
• Genealogical DNA test
• Genetic deletion
• List of number of chromosomes of various organisms

External links

• What Can Our Chromosomes Tell Us?,an accessible and comprehensive look at chromosomes, from the University of Utah's Genetic Science Learning Center
• Try making a karyotype yourself, from the University of Utah's Genetic Science Learning Center
• Kimballs Chromosome pages
• Chromosome News from Genome News Network
• European Chromosome 11q Network
• Eurochromnet, European network for Rare Chromosome Disorders on the Internet
• http://www.ensembl.org Ensembl project, presenting chromosomes, their genes and syntenic loci graphically via the web
• A Yahoo! group for Isodicentric 15

References

Evolution of chromosomes  •  • [ e]
Basic topics: Chromosome | Karyotype | Ploidy | Meiosis
Classification: Autosome | Sex chromosome
Evolution: Chromosomal inversion | Chromosomal translocation | Polyploidy