Chapter 6

Genetic materials.
Chromosome structure.
Chromosome variation.
Hang Tong, SBT
1. Genetic materials

Characteristics of genetic materials

Proof that genetic information is stored in
DNA

Structure of DNA and RNA
1.1. Characteristics of genetic material

Contain the complex information
 Information for all trait
 Capacity to vary
 Stable

Replicate faithfully
 Copy correctly to be transferred to
progeny

Encode phenotype
 Determine traits
1.2.The molecular basis of heredity

Many scientists contributed to our understanding

of DNA as/and source of genetic materials
The discovery of transforming principles


In 1928, Griffith studies pneumonia pathogen
Streptococcus pneumonia

S. pneu bacterium exists in 1 of 2 forms: smooth
and rough

Griffith infected mouse with several vials of
bacteria and he got an unusual result
Identification of transforming principle

Avery repeated Griffith experiments and attempted
to find out transforming factor

Avery treated virulent sample train (S) with
different enzymes (protease, RNAse, DNAse) and
then mix with avirulent strain (R )

Avery found that only DNAse-treated sample did
not form the S strain again but other samples did
 S strain is homogenized

… then divided into 3 vials to treat

with different enzymes

The enzyme treated extract are

mixed with R strain

S strains are reformed again in only

protease-treated and RNAse-treated
samples but not in DNAse-treated sample

Conclusion : DNA is
transforming principle
Hershey – Chase experiment

The experiment attempted to study the genetic material
by using T2 phage to infect E.coli bacteria

They used the radioactive P and S to stain DNA and
protein, respectively.

They determined the transforming and coding factors
(protein or DNA)

When infecting, virus

pumps its nucleus into
bacterial cell and protein
remains outside.
Watson – Crick 's discovery

Watson and Crick worked on the structure of DNA
by using all available information (transformable,
coding, chemical properties...) to build up the
handed helix of molecule

At the same time, Wilkins and Franklin also worked
on DNA structure but using X-ray diffraction

Together, 4 scientists have found the double helix
structure of DNA and have awarded Nobel Prize in
1962
1.3. DNA structure
Nucleotides- Base
Nucleotides- Sugars and phosphate groups
Linkage
Secondary structure

B-DNA structure consists of
anpha helix with
approximately 10 bases per
turn
Special structure in DNA and RNA
• Double stranded DNA with pairing of base proves
stability and produces the helical structure of the
molecules
• Single stranded DNA and RNA lack the stabilizing
influence of the pairing nucleotides so they exhibit
the un common structures
• The internal base pairing impact the single strand
to specific secondary structure
Consist of the region of
paired bases (stem) and
region of unpaired bases
(loop)

A stem with no loop

Secondary structure showing
many hairpins (found in
RNAse P of E.coli)
A cruciform structure
Bending in DNA
DNA can be bended by binding of the protein to specific
DNA sequences
2. Chromosome structures

• Bacterial chromosomes
• Eukaryotic chromosomes
2.1. Bacterial chromosomes
• Normally consists of a single circular DNA molecule
• Bacterial DNA is complexed with proteins to
compact it
• If the bacterial cell is broken open gently, DNA spills
out in a series of loops. The ends of loops are mostly
held by proteins that makes DNA condensed
• May bacteria contain the additional circular DNA
molecules called plasmids which replicate
independently of the chromosome
Bacterial long chromosome is folded in loops
- By DNA binding proteins (or histone-like protein): HU protein,
integration host factor (IHF), protein H1, protein HLP1, protein H
By twisting the loop to form supercoil
Bacterial plasmids
- In addition to having chromosome, many bacteria
contain small circular DNA molecules called
plasmids
- Plasmids present in the cell in different copy numbers
- In general, plasmid carries genes that are not
necessary to bacterial function but some may play
roll in host life cycle or growth….
- Plasmid possesses its own origin of replication and
can replicate independently of the chromosome
2.2. The eukaryotic chromosomes
- an eukaryote has number of chromosomes, each
contains a single, extremely long DNA
molecule.
- to fit DNA into nucleus, this DNA molecule
should change its structure through time.
- in the course of cell cycle, DNA packaging
changes from highly condensed to released state
Chromatin

To pack into the high condensed state, DNA is associated
with number of protein histone → chromatin

There are 2 types of chromatin: euchromatin (which
undergoes the normal process of condensation and
decondensation in the cell cycle – found as the major
genetic material of the cell) and heterochromatin (stayed in
the high condensed state through out cell cycle – found at
the centromeres and telomeres of all chromosomes))
 Proteins

The most abundant protein found in chromatin structure is
histon: small, positive charged of 5 types

The assortment of nonhiston chromosomal protein makes up

about a half of protein mass in chromosome structure

Other protein component includes scaffold protein, proteins
that make up the kinetochore, motor proteins that move protein
in mitosis and meiosis
Nucleosomes
- Nucleosome structure
reveals when adding
nuclease to degrade DNA
linking components
- nucleosome contains 8
protein histone molecules of 4
pairs: H2A, H2B, H3, H4
- H1 works to place DNA and
lock it with other histones
- structure of nucleosome and
H1 is called chromatosome
 30-40 bp

167 bp in
chromatosome
Higher order chromatin structure

Fiber: nucleosomes fold on themselves to form the
dense, highly packed structure

Loops: fiber of nucleosome fold with nuclear scaffold
proteins to form 300 nm loops


Loops continue coiling to form 250 nm wide fiber.
The highly coiling of this fiber makes the
chromosome structure that seen in metaphase.
Changes in chromatin structure

Polytene chromosome:

Giant chromosomes found in the certain tissue
of some dipteran organisms (two-wings)

Arise when chromosomal replication takes
place without cell division producing thousand
of DNA copies lying side by side

Contain the active regions of transcription, this
associates with gene activity (specially when
exposed to specific hormones)

The structure change with gene activity
property is sensitive to DNAse
Polytene chromosomes of Drosophila
melanogaster with 4 giant
chromosomes attached
 NA

DNAseI cuts DNA molecules

when DNA is in relaxed form
(which does not associate with
protein – chromosome is active
and ready for gene expression)
 Centromere structure

Centromere is the region of chromosome where spindle
fibers attach and it is essential for chromosome movement
in cell division (See more the experiment that proved the
role of centromere) and help to control the cell cycle

The molecular structure has recently been revealed

Some organisms have localized centromere on
chromosome (which allows spindle fiber attached to
specific position in chromosome) while others have
chromosome with diffuse centromere (spindle attaches
along the entire length of chromosome)

Two major classes of localzed centromere are point
centromere and regional centromere

Point centromeres are generally small (point centromere
of budding yeast consists of 125 bp)

Regional centromeres are found in fission yeast and most
of plant and animal

Consist of particular sequences repeated many times but
there is no unique sequence

Centromere sequence of budding yeast Saccharomyces cerevisae)

Telomere structure

Telomere: the natural ends of chromosome that serve
as cap to stabilize chromosome structure

Telomere DNA is not replicated by normal DNA
synthesis DNA enzyme, so each time replicate,
chromosome is shortened, and cell can divide for
limited times.

In germ cells, the enzyme telomerase work to replicate
telomere, so these cells can devide continuously

Telomere sequences usually consist of a series of
nucleotide C followed by several nucleotide A or T or
both. Sequence may be repeated from 250 to 1500
times
 3. Chromosome variation
- chromosomes exist in one of the 4 normal forms and number
(as seen in karyotype)

- variation in chromosome structure and number results in

function and expression
 1p31.1

https://www.ncbi.nlm.nih.gov/Class/MLACourse/Modules/Genomes/map_cytogenetic_bands.html

For example:
- gene for ACADM (acyl-Coenzyme A dehydrogenase, C-4 to C-12 straight chain)
locates at 1p31.1
- Gene for Magnesium transporter protein 1 locates at Xq21.1
Types of chromosome mutations


Chromosome rearrangement: alter the structure of
chromosome (repeat, delete or invert chromosome
fragments)

Aneuploidy: number of chromosome altered,
chromosome is added or deleted

Polyploidy: one or more complete sets of
chromosome are added
3.1. Chromosome rearrangement

Duplication

Part of chromosome is duplicated

Duplication might be tandem (duplicated region
adjacent to origin region), or displaced (not
adjacent), or reversed (duplicated region is inverted)

Duplication may have major effect on phenotypes

Deletion

Loss of chromosome segments,
chromosome s shortened.

Depending on which genes are lost, the
effect may varied, but generally it is
serious, many are lethal
Notch gene is deleted,
results in changed wing
structure

Inversion

Chromosome segment is inverted

No gain or loss gene function

Effect may occur with gene that position
specific

Translocation

Movement of genetic material between
nonhomologous chromosomes or within
the same chromosome
3.2. Aneuploidy

Number of individual chromosome changed

Chromosomes may be lost in mitosis if they
can not divide equally into daughter cells

Types of aneuploidy

Nullisomy: loss of both member of
homologous chromosomes (2n – 2)

Monosomy: loss of single chromosome (2n –
1)

Trisomy: gain of single chromosome (2n+1)

Tetrasomy: gain of 2 homologous
chromosomes (2n + 2)

Effect of aneuploidy

Alter the phenotype drastically, in most of
plant and animal, this is lethal due to abnomal
gene dossage
3.3. Polyploidy

The whole set of chromosome is replicated
leading to polyploidy

Includes: triploid (3n), tetraploid (4n),
pentaploid (5n) and even higher number of
chromosome set

Common seen in plants and is major
mechanism by which new plants envolve

Autopolyploidy: results when accidence of mitosis or meiosis
produce extra set of chromosomes

Allopolyploidy: arise from
hybridization between 2 species
resulting the polyploidy set carry
chromosomes from 2 species
3.4. Chromosome mutations and cancer