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Chromosome Organization and
Molecular Structure
• Chromosomes are the structures that contain the
genetic material
– They are complexes of DNA and proteins
• The genome comprises all the genetic material
that an organism possesses
– In bacteria, it is typically a single circular chromosome
– In eukaryotes, it refers to one complete set of nuclear
chromosomes
– Note:
• Eukaryotes possess a mitochondrial genome
• Plants also have a chloroplast genome
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• The main function of the genetic material is to store
information required to produce an organism
– The DNA molecule does that through its base sequence
• DNA sequences are necessary for
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–
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1.
2.
3.
4.
Synthesis of RNA and cellular proteins
Replication of chromosomes
Proper segregation of chromosomes
Compaction of chromosomes
• So they can fit within living cells
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VIRAL GENOMES
• Viruses are small infectious particles containing
nucleic acid surrounded by a capsid of proteins
• For replication, viruses rely on their host cells
– ie., the cells they infect
• Most viruses exhibit a limited host range
– They typically infect only specific types of cells of one
host species
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
Bacteriophages may also contain a sheath, base plate and
tail fibers
General structure of viruses
• During an infection process, mature viral particles
need to be assembled

Viruses with a
simple structure
may self-assemble

Genetic material
and capsid proteins
spontaneously bind
to each other

Example: Tobacco
mosaic virus
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• Bacterial chromosomal DNA is usually a circular
molecule that is a few million nucleotides in length
– Escherichia coli  ~ 4.6 million base pairs
– Haemophilus influenzae  ~ 1.8 million base pairs
• A typical bacterial chromosome contains a few
thousand different genes
– Structural gene sequences (encoding proteins) account
for the majority of bacterial DNA
– The nontranscribed DNA between adjacent genes are
termed intergenic regions
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A few hundred
nucleotides in length
These play roles in DNA
folding, DNA replication, gene
regulation, and genetic
recombination
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• To fit within the bacterial cell, the chromosomal DNA must
be compacted about a 1000-fold
– This involves the formation of loop domains
The looped structure compacts
the chromosome about 10-fold

The number of loops varies according to the size of the
bacterial chromosome and the species

E. coli has 50-100 with 40,000 to 80,000 bp of DNA in each
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• DNA supercoiling is a second important way to
compact the bacterial chromosome
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EUKARYOTIC CHROMOSOMES
• Eukaryotic species contain one or more sets of
chromosomes
Each set is composed of several different linear
chromosomes
• The total amount of DNA in eukaryotic species is typically
greater than that in bacterial cells
• Chromosomes in eukaryotes are located in the nucleus
– To fit in there, they must be highly compacted
• This is accomplished by the binding of many proteins
• The DNA-protein complex is termed chromatin
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Has a genome that is more than
twice as large as that of
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Eukaryotic chromosomes
contain many origins of
replication approximately
100,000 bp apart
Required for proper
segregation during
mitosis and meiosis
Kinetochore proteins
link the centromere to
the spindle apparatus
Prevent chromosome sticky ends
which could lead to
translocations and shortening
Repetitive Sequences
• Sequence complexity refers to the number of
times a particular base sequence appears in
the genome
• There are three main types of repetitive
sequences
– Unique or non-repetitive
– Moderately repetitive
– Highly repetitive
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Repetitive Sequences
• Unique or non-repetitive sequences
– Found once or a few times in the genome
– Includes structural genes as well as intergenic areas
– In humans, make up roughly 41% of the genome
• Moderately repetitive
– Found a few hundred to a few thousand times
– Includes
•
•
•
•
Genes for rRNA and histones
Origins of replication
Sequences that regulate gene expression and translation
Transposable elements
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Repetitive Sequences
• Highly repetitive
– Found tens of thousands to millions of times
– Each copy is relatively short (a few nucleotides to several
hundred in length)
– Some sequences are interspersed throughout the genome
• Example: Alu family in humans
– Represents 10% of human genome
– Found every 5-6000 bp
– Other sequences are clustered together in tandem arrays
• Example: AATAT and AATATAT sequences in Drosophila
• These are commonly found in the centromeric regions
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Introduction to chromatin structure
• Chromatin is a complex made up of DNA and
proteins.
– The proteins consist of the basic histone proteins
and some nonhistone proteins.

Histone proteins are basic
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They contain many positively-charged amino acids
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Lysine and arginine
These bind with the phosphates along the DNA backbone
Histone proteins have a globular domain and a flexible,
charged amino terminus or ‘tail’
There are five types of histones
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H2A, H2B, H3 and H4 are the core histones
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Two of each make up the octamer
H1 is the linker histone
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
Binds to linker DNA
Also binds to nucleosomes

But not as tightly as are the core histones
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Vary in length between 20 to 100 bp,
depending on species and cell type
Diameter of the
nucleosome

Overall structure of connected nucleosomes resembles “beads on a string”
 This structure shortens the DNA length about seven-fold
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Play a role in the organization
and compaction of the
chromosome
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Irregular
configuration where
nucleosomes have
little face-to-face
contact
Regular, spiral
configuration
containing six
nucleosomes
per turn
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The nuclear matrix is
hypothesized to be an
intricate fine network of
irregular protein fibers
plus many other
proteins bound to these
fibers. This structure is
very dynamic and
complex.
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
The third mechanism of DNA compaction involves the
formation of radial loop domains
Matrix-attachment
regions
or
Scaffold-attachment
regions (SARs)
25,000 to
200,000 bp
MARs are anchored
to the nuclear matrix,
thus creating radial
loops
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Further Compaction of the Chromosome
1
1
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2
3
2
3
2
4
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5
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3
6
Z
5
2
4
Z
(a) Metaphase chromosomes
1
3
Z
5
(b) Chromosomes in the cell nucleus during interphase
Each of seven types of chicken chromosomes is labeled a
different color. Each occupies a specific territory during
interphase.
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2mm
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There are two types of heterochromatin
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Constitutive heterochromatin
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Regions that are always heterochromatic
Permanently inactive with regard to transcription
Usually contain highly repetitive sequences
Facultative heterochromatin
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Regions that can interconvert between euchromatin and
heterochromatin
Example: Barr body formation during development in female
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The levels of
compaction
leading to a
metaphase
chromosome
Compaction level
in euchromatin
During interphase
most chromosomal
regions are
euchromatic
Compaction level
in heterochromatin
Metaphase Chromosomes
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The number of loops has not changed
However, the diameter of each loop is smaller
During interphase,
condensin is in the
cytoplasm
Condensin binds
to chromosomes
and compacts the
radial loops
Condensin
travels into the
nucleus
The condensation of a metaphase chromosome by condensin
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Cohesins along
chromosome arms are
released
The alignment of sister chromatids via cohesin
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