A
chromosome is an organized structure of
DNA and
protein that is found in
cells. It is a single piece of coiled DNA containing many
genes,
regulatory elements and other
nucleotide sequences. Chromosomes also contain DNA-bound proteins, which serve to package the DNA and control its functions. The word
chromosome comes from the
Greek (
chroma, color) and (
soma, body) due to their property of being very strongly stained by particular
dyes.
thumb|250px|Diagram of a duplicated and condensed [[metaphase eukaryotic chromosome. (1)
Chromatid – one of the two identical parts of the chromosome after
S phase. (2)
Centromere – the point where the two chromatids touch, and where the microtubules attach. (3) Short arm. (4) Long arm.]]
Chromosomes vary widely between different
organisms. The DNA molecule may be circular or linear, and can be composed of 10,000 to 1,000,000,000
nucleotides in a long chain. Typically
eukaryotic cells (cells with nuclei) have large linear chromosomes and
prokaryotic cells (cells without defined nuclei) have 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 chromosomes.
In eukaryotes, nuclear chromosomes are packaged by proteins into a condensed structure called
chromatin. This allows the very long DNA molecules to fit into the
cell nucleus. The structure of chromosomes and chromatin varies through the
cell cycle. Chromosomes are the essential unit for cellular division and must be replicated, divided, and passed successfully to their daughter cells so as to ensure the genetic diversity and survival of their
progeny. Chromosomes may exist as either duplicated or unduplicated—unduplicated chromosomes are single linear strands, whereas duplicated chromosomes (copied during
synthesis phase) contain two copies joined by a
centromere. Compaction of the duplicated chromosomes during
mitosis and
meiosis results in the classic four-arm structure (pictured to the right). Chromosomal recombination plays a vital role in genetic diversity. If these structures are manipulated incorrectly, through processes known as chromosomal instability and translocation, the cell may undergo
mitotic catastrophe and die, or it may aberrantly evade
apoptosis leading to the progression of cancer.
In practice "chromosome" is a rather loosely defined term. In prokaryotes and
viruses, the term
genophore is more appropriate when no chromatin is present. However, a large body of work uses the term chromosome regardless of chromatin content. In prokaryotes DNA is usually arranged as a circle, which is tightly coiled in on itself, sometimes accompanied by one or more smaller circular DNA molecule called a
plasmid. These small circular genomes are also found in mitochondria and chloroplasts, reflecting their bacterial origins. The simplest genophores are found in viruses: these DNA or RNA molecules are short linear or circular genophores that often lack structural proteins.
History
Nucleus as the seat of heredity
The origin of this groundbreaking idea lies in a few sentences tucked away in
Ernst Haeckel's
Generelle Morphologie of 1866. The evidence for this insight gradually accumulated until, after twenty or so years, two of the greatest in a line of great German scientists spelled out the concept.
August Weismann proposed that the
germ line is separate from the
soma, and that the cell nucleus is the repository of the hereditary material, which, he proposed, is arranged along the chromosomes in a linear manner. Further, he proposed that at fertilisation a new combination of chromosomes (and their hereditary material) would be formed. This was the explanation for the reduction division of
meiosis (first described by van Beneden).
Chromosomes as vectors of heredity
In a series of experiments,
Theodor Boveri gave the definitive demonstration that chromosomes are the
vectors of heredity. His two principles were based upon the
continuity of chromosomes and the
individuality of chromosomes.
It is the second of these principles that was so original. Boveri was able to test the proposal put forward by
Wilhelm Roux, that each chromosome carries a different
genetic load, and showed that Roux was right. Upon the rediscovery of Mendel, Boveri was able to point out the connection between the rules of inheritance and the behaviour of the chromosomes. It is interesting to see that Boveri influenced two generations of American cytologists:
Edmund Beecher Wilson,
Walter Sutton and
Theophilus Painter were all influenced by Boveri (Wilson and Painter actually worked with him).
In his famous textbook
The Cell, Wilson linked Boveri and Sutton together by the
Boveri-Sutton theory. Mayr remarks that the theory was hotly contested by some famous geneticists:
William Bateson,
Wilhelm Johannsen,
Richard Goldschmidt and
T.H. Morgan, all of a rather dogmatic turn-of-mind. Eventually complete proof came from chromosome maps in Morgan's own lab.
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
thumb|right|350px|Fig. 2: The major structures in DNA compaction; [[DNA, the
nucleosome, the 10nm "beads-on-a-string" fibre, the 30nm fibre and the
metaphase chromosome.]]
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., 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 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
thumb|200px|right|Human chromosomes during metaphase.
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
The prokaryotes –
bacteria and
archaea – typically have a single circular chromosome, but many variations do exist. Most bacteria have a single circular chromosome that can range in size from only 160,000
base pairs in the
endosymbiotic bacterium
Candidatus Carsonella ruddii, to 12,200,000 base pairs in the soil-dwelling bacterium
Sorangium cellulosum.
Spirochaetes of the
genus Borrelia are a notable exception to this arrangement, with bacteria such as
Borrelia burgdorferi, the cause of
Lyme disease, containing a single linear chromosome.
Structure in sequences
Prokaryotic chromosomes have less sequence-based structure than eukaryotes. Bacteria typically have a single point (the
origin of replication) from which replication starts, whereas some archaea contain multiple replication origins. The genes in prokaryotes are often organized in
operons, and do not usually contain
introns, unlike eukaryotes.
DNA packaging
Prokaryotes do not possess nuclei. Instead, their DNA is organized into a structure called the
nucleoid. 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. In
archaea, the DNA in chromosomes is even more organized, with the DNA packaged within structures similar to eukaryotic nucleosomes.
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).
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
These tables give the total number of chromosomes (including sex chromosomes) in a cell nucleus. For example, human cells are
diploid and have 22 different types of
autosome, each present as two copies, and two
sex chromosomes. This gives 46 chromosomes in total. Other organisms have more than two copies of their chromosomes, such as
bread wheat, which is
hexaploid and has six copies of seven different chromosomes – 42 chromosomes in total.
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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.
thumb|200px|left|The 24 human chromosome territories during prometaphase in fibroblast cells.
Asexually reproducing species have one set of chromosomes, which are the same in all body cells. However, asexual species can be either haploid or diploid.
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. Plants important in agriculture 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.
Prokaryotes
Prokaryote species generally have one copy of each major chromosome, but most cells can easily survive with multiple copies. For example,
Buchnera, a
symbiont of
aphids has multiple copies of its chromosome, ranging from 10–400 copies per cell. However, in some large bacteria, such as
Epulopiscium fishelsoni up to 100,000 copies of the chromosome can be present. Plasmids and plasmid-like small chromosomes are, as 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
thumb|right|200px|Figure 3: Karyogram of a human maleIn general, the
karyotype is the characteristic chromosome complement of a
eukaryote species. The preparation and study of karyotypes is part of
cytogenetics.
Although the
replication and
transcription of
DNA 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 the
germ-line and
soma (between
gametes and the rest of the body); 3. variation between members of a population, due to
balanced genetic polymorphism; 4.
geographical variation between
races; 5.
mosaics or otherwise abnormal individuals. Also, variation in karyotype may occur during development from the fertilised egg.
The technique of determining the karyotype is usually called
karyotyping. 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
karyogram, with the set of chromosomes arranged, autosomes in order of length, and sex chromosomes (here X/Y) at the end: Fig. 3.
Like many sexually reproducing species, humans have special
gonosomes (sex chromosomes, in contrast to
autosomes). These are XX in females and XY in males.
Historical note
Investigation into the human karyotype took many years to settle the most basic question. How many chromosomes does a normal
diploid human cell contain? In 1912,
Hans von Winiwarter reported 47 chromosomes in
spermatogonia and 48 in
oogonia, concluding an
XX/XO sex determination mechanism.
Painter in 1922 was not certain whether the diploid number of man is 46 or 48, at first favouring 46. He revised his opinion later from 46 to 48, and he correctly insisted on man's having an
XX/XY system.
New techniques were needed to definitively solve the problem:
1. Using cells in culture
2. Pretreating cells in a
hypotonic solution, which swells them and spreads the chromosomes
4. Squashing the preparation on the slide forcing the chromosomes into a single plane
5. Cutting up a photomicrograph and arranging the result into an indisputable karyogram.
It took until the mid-1950s for it to become generally accepted that the human karyotype include only 46 chromosomes. Considering the techniques of Winiwarter and Painter, their results were quite remarkable. Chimpanzees (the closest living relatives to modern humans) have 48 chromosomes.
Chromosomal aberrations
thumb|right|The three major single chromosome mutations; deletion (1), duplication (2) and inversion (3).thumb|right|The two major two-chromosome mutations; insertion (1) and translocation (2).In Down syndrome, there are three copies of chromosome 21|thumbChromosomal 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 birthing 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 DNA from chromosomes 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 those of 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 syndrome, usually is 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 mental retardation.
- Edwards syndrome, which is the second-most-common trisomy; Down syndrome is the most common. 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 that live past their first birthday usually are quite healthy thereafter. They have a characteristic 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. 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.
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.
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. 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.
File:Genes and bases on chromosomes.png See also
- Locus (explains gene location nomenclature)
