CHROMOSOME STRUCTURE
Chromosomes were first observed in plant cells by Karl Wilhelm von Nageli in 1842. Their
behavior in animal (Salmander) cells was described by Walter Flemming, the discoverer of
Mitosis, in 1882. The name was coined by another Germen anatomist, von Waldeyer in 1888.
But it took until the mid 1950s to became generally accepted that the karyotype of man
included only 46 chromosomes.
A chromosome is, minimally, a very long, continuous piece of DNA and so it is responsible
for transmitting genetic information. In chromosomes of eukaryotes, uncondensed DNA
exists in a quasi-ordered structure inside the nucleus, where it wraps around histones
(structural proteins and where the composition material is called chromatin). During mitosis
(cell division), the chromosomes are condensed and called metaphasic chromosomes. This is
the only natural context in which individual chromosomes are visible with and optical
microscope.
Chromosomes in Bacteria
Bacterial chromosomes are often circular but sometimes linear. Some bacteria have one
chromosome, while other have few. Bacterial DNA also exists as plasmids.
Eukaryotic Chromosome Structure
The length of DNA in the nucleus is far greater than the size of the compartment in which it
is contained. To fit into this compartment the DNA has to be condensed in some manner. The
degree to which DNA is condensed is expressed as its packing ratio.
To achieve the overall packing ratio, DNA is not packaged directly into final structure of
chromatin. Instead, it contains several hierarchies of organization. The first level of packing
is achieved by the winding of DNA around a protein core to produce a "bead-like" structure
called a nucleosome. This structure is invariant in both the euchromatin and heterochromatin
of all chromosomes. The second level of packing is the coiling of beads in a helical structure
called the 30 nm fiber that is found in both interphase chromatin and mitotic chromosomes.
The final packaging occurs when the fiber is organized in loops, scaffolds and domains that
give a final packing ratio of about 1000 in interphase chromosomes and about 10,000 in
mitotic chromosomes.
Eukaryotic chromosomes consist of a DNA-protein complex that is organized in a compact
manner which permits the large amount of DNA to be stored in the nucleus of the cell. The
subunit designation of the chromosome is chromatin. The fundamental unit of chromatin is
the nucleosome.
Chromatin - the unit of analysis of the chromosome; chromatin reflects the general structure
of the chromosome but is not unique to any particular chromosome
Nucleosome - simplest packaging structure of DNA that is found in all eukaryotic
chromosomes; DNA is wrapped around an octamer of small basic proteins called histones;
146 bp is wrapped around the core and the remaining bases link to the next nucleosome; this
structure causes negative supercoiling
The nucleosome consists of about 200 bp wrapped around a histone octamer that contains
two copies of histone proteins H2A, H2B, H3 and H4. These are known as the core histones.
Histones are basic proteins that have an affinity for DNA and are the most abundant proteins
associated with DNA. The amino acid sequence of these four histones is conserved
suggesting a similar function for all.
The length of DNA that is associated with the nucleosome unit varies between species. But
regardless of the size, two DNA components are involved. Core DNA is the DNA that is
actually associated with the histone octamer. This value is invariant and is 146 base pairs.
The core DNA forms two loops around the octamer, and this permits two regions that are 80
bp apart to be brought into close proximity. Thus, two sequences that are far apart can
interact with the same regulatory protein to control gene expression. The DNA that is
between each histone octamer is called the linker DNA and can vary in length from 8 to 114
base pairs. This variation is species specific, but variation in linker DNA length has also been
associated with the developmental stage of the organism or specific regions of the genome.
The next level of organization of the chromatin is the 30 nm fiber. This appears to be a
solenoid structure with about 6 nucleosomes per turn. This gives a packing ratio of 40, which
means that every 1 µm along the axis contains 40 µm of DNA. The stability of this structure
requires the presence of the last member of the histone gene family, histone H1. Because
experiments that strip H1 from chromatin maintain the nucleosome, but not the 30 nm
structure, it was concluded that H1 is important for the stabilization of the 30 nm structure.
The final level of packaging is characterized by the 700 nm structure seen in the metaphase
chromosome. The condensed piece of chromatin has a characteristic scaffolding structure that
can be detected in metaphase chromosomes. This appears to be the result of extensive
looping of the DNA in the chromosome.
A solenoid model of chromatin with 10nm nu bodies linked by spacer DNA;
binding of H1 makes the nucleotide thread into coiled threads
Chromatin consists of DNA molecules that are spooled around a cylindrical structure made
of histone proteins. There are four so-called “core histones” that compose the cylinders and
the DNA winds around these histone cores. Then a non-core histone called H1 pulls the
histone cylinders with their DNA wound about them together to form higher-order structures.
The histone cylinders wound about with DNA are called “nucleosomes” or “core particles.”
The assembled clusters to nucleosomes are called “30 nanometer solenoids.
The last definitions that need to be presented are euchromatin and heterochromatin. When
chromosomes are stained with dyes, they appear to have alternating lightly and darkly stained
regions. The lightly-stained regions are euchromatin and contain single-copy, geneticallyactive DNA. The darkly-stained regions are heterochromatin and contain repetitive sequences
that are genetically inactive.
Centromeres and Telomeres
Centromeres and telomeres are two essential features of all eukaryotic chromosomes. Each
provide a unique function that is absolutely necessary for the stability of the chromosome.
Centromeres are required for the segregation of the centromere during meiosis and mitosis,
and teleomeres provide terminal stability to the chromosome and ensure its survival.
Centromeres are those condensed regions within the chromosome that are responsible for
the accurate segregation of the replicated chromosome during mitosis and meiosis. When
chromosomes are stained they typically show a dark-stained region that is the centromere.
During mitosis, the centromere that is shared by the sister chromatids must divide so that the
chromatids can migrate to opposite poles of the cell. On the other hand, during the first
meiotic division the centromere of sister chromatids must remain intact, whereas during
meiosis II they must act as they do during mitosis. Therefore the centromere is an important
component of chromosome structure and segregation.
Within the centromere region, most species have several locations where spindle fibers
attach, and these sites consist of DNA as well as protein. The actual location where the
attachment occurs is called the kinetochore and is composed of both DNA and protein. The
DNA sequence within these regions is called CEN DNA. Because CEN DNA can be moved
from one chromosome to another and still provide the chromosome with the ability to
Telomeres are the region of DNA at the end of the linear eukaryotic chromosome that are
required for the replication and stability of the chromosome.
Types of Chromosomes
Metacentric Chromosomes
Metacentric chromosomes have the centromere in the center, such that both sections are of
equal length. Human chromosome 1 and 3 are metacentric.
Submetacentric Chromosomes
Submetacentric chromosomes have the centromere slightly offset from the center leading to a
slight asymmetry in the length of the two sections. Human chromosomes 4 through 12 are
submetacentric.
Acrocentric Chromosomes
Acrocentric chromosomes have a centromere which is severely offset from the center leading
to one very long and one very short section. Human chromosomes 13,15, 21, and 22 are
acrocentric.
Telocentric Chromosomes
Telocentric chromosomes have the centromere at the very end of the chromosome. Humans
do not possess telocentric chromosomes but they are found in other species such as mice.
Eukaryotic Chromosome Karyotype
Whereas bacteria only have a single chromosome, eukaryotic species have at least one pair of
chromosomes. Most have more than one pair. Another relevant point is that eukaryotic
chromosomes are detected only occur during cell division and not during all stages of the cell
cycle. They are in their most condensed form during metaphase when the sister chromatids
are attached. This is the primary stage when cytogenetic analysis is performed.
Each species is characterized by a karyotype. The karyotype is a description of the number
of chromosomes in the normal diploid cell, as well as their size distribution. For example, the
human chromosome has 23 pairs of chromosome, 22 somatic pairs and one pair of sex
chromosomes. One important aspect of genetic research is correlating changes in the
karyotype with changes in the phenotype of the individual.
One important aspect of genetics is correlating changes in karyotype with changes in
phenotype. For example, humans that have an extra chromosome 21 have Down's syndrome.
Insertions, deletions and changes in chromosome number can be detected by the skilled
cytogeneticist, but correlating these with specific phenotypes is difficult.
The first discriminating parameter when developing a karyotype is the size and number of the
chromosomes. Although this is useful, it does not provide enough detail to be begin the
development of a correlation between structure and function (phenotype). To further
distinguish among chromosomes, they are treated with a dye that stains the DNA in a
reproducible manner. After staining, some of the regions are lightly stained and others are
heavily stained. As described above, the lightly stained regions are called euchromatin, and
the dark stained region is called heterochromatin. The current dye of chose is the Giemsa
stain, and the resulting pattern is called the G-banding pattern.
C-Value Paradox
In addition to describing the genome of an organism by its number of chromosomes, it is also
described by the amount of DNA in a haploid cell. This is usually expressed as the amount of
DNA per haploid cell (usually expressed as picograms) or the number of kilobases per
haploid cell and is called the C value. One immediate feature of eukaryotic organisms
highlights a specific anomaly that was detected early in molecular research. Even though
eukaryotic organisms appear to have 2-10 times as many genes as prokaryotes, they have
many orders of magnitude more DNA in the cell. Furthermore, the amount of DNA per
genome is correlated not with the presumed evolutionary complexity of a species. This is
stated as the C value paradox: the amount of DNA in the haploid cell of an organism is
not related to its evolutionary complexity. (Another important point to keep in mind is that
there is no relationship between the number of chromosomes and the presumed evolutionary
complexity of an organism.)