Genome Organization and

Structure of DNA

Medical Faculty 1st Year, Committee III

Dr. Sevgi Gezici

December 27, 2023
 Genome Organization
The heredity material i.e. DNA (deoxyribonucleic acid) of
an organism is composed of a sequence of
four nucleotides in a specific pattern, which encode
information as a function of their order.

Genomic organization refers to the linear order of DNA

elements and their division into chromosomes.

"Genome organization" can also refer to the 3D structure

of chromosomes and the positioning of DNA
sequences within the nucleus.
 Structure of DNA
 DNA is made up of molecules called
nucleotides.
 Each nucleotide contains a phosphate
group, a sugar group and a nitrogen
base.
 The four types of nitrogen bases are
adenine (A), thymine (T), guanine (G)
and cytosine (C).
 The order of these bases is what
determines DNA's instructions, or
genetic code.
 Human DNA has around 3 billion bases,
and more than 99 percent of those bases
are the same in all people, according to
the U.S. National Library of
Medicine (NLM).
 Structure of DNA
• Nucleotides are attached together to form two long strands that spiral to
create a structure called double helix. DNA molecules are long enough, that
they can't fit into cells without the right packaging.
• To fit inside cells, DNA is coiled tightly to form structures are
called chromosomes. Humans have 23 pairs of chromosomes, which are
found inside the cell's nucleus.
 What Cellular Structure Holds the Genetic
Information?
• Chromosomes
– Contain the
genetic material:
DNA, RNA

• Chromatin
– Is the
chromosomal
material in its
decondensed,
threadlike state.
 Mitosis
• Form of asexual
reproduction.
• Occurs when organism
grows or replaces damaged
cells.
• Prior to mitosis, cell
undergoes replication.
– Process in which chromatin is
copied.
• Produces diploid cells.
 Prophase
• Start of mitosis
• Chromatin condenses
into rod-like
chromosomes
– Each chromosome
consists of sister
chromatids, connected
at the centromere
• Nuclear membrane
disappears
 Metaphase
• Chromosomes align
themselves in flat plane
at cell equator.
 Anaphase
• Centromeres split.
• Sister chromatids-now
chromosomes- are
pulled to opposite poles
of the cell.
 Telophase
• Chromosomes unravel,
returning the chromatin
to its non-dividing
threadlike state.
• Nuclear membrane
assembles.
 Cytokinesis
• Division of the
cytoplasm.
• Begins during anaphase
and telophase.
 Cytokinesis
• Differs in animals and
plant cells.
• Plant cells form a cell
plate.
– membranous vesicles
congregate at center of
cell.
– Vesicles contain cell wall
material.
 Cytokinesis
• Animal cells form a
cleavage furrow.
– Forms around the
periphery of the dividing
cell.
– Furrow becomes deeper
and deeper until
membrane pinches off
forming two cells.
 Chromosomes Come in Matched Pairs
• Homologous pairs:
chromosomes that are
closely matched in size
and shape
– Determine the same
traits
– The nucleus is the organelle that
contains our genetic material in
the form of 23 pairs
of chromosomes (46 total). Every
chromosome is a very long strand
of DNA.

• Sex chromosomes: Those that determine the

gender of the organism.
 Chromosomal Theory of Inheritance
• The two members of each pair of a homologous pair
of chromosomes carry alleles for the same genes
and, therefore, affect the same traits.
• Proposed in 1903.
 Chromosomal Theory of Inheritance
The Chromosomal Theory of Inheritance supports Mendel’s laws. Listed below are the
observations of this theory:

• During the process of cell division-meiosis, the pairs of homologous chromosome

move as discrete structures, which are independent of other pairs of
chromosomes.
• There is a random distribution of chromosomes into the pre-gametes from each
homologous pair.
• Each parent synthesizes gametes, which constitute only half of their chromosomal
complement.
• Even though female (egg) and male (sperm) gametes differ in their size and
morphology, they have the same number of chromosomes, submitting equal genetic
contributions from each parent.
• The gametic chromosomes fuse during fertilization to produce offspring with the
same number of a chromosome as their parents.
 Mapping genes

• Locus: location of a gene on a chromosome.

• Currently trying to map all human genes to the appropriate
chromosome.
• Ex: gene responsible for sickle cell anemia is located on
chromosome 11.
 Sexual reproduction
• Type of reproduction in
which genetic
information from
female combines with
male.
• Requires fertilization
– Fusion of gametes (egg
and sperm)
– These cells need to have
half the amount of
genetic information.
 Meiosis
• Produces haploid cells
(gametes-eggs and sperm)
– Posses only one member of
each pair of homologous
chromosomes
• Chromosomes replicate
before meiosis.
• Requires two rounds of
division.
 Prophase I
• Chromatin condenses into
compact chromosomes.
• Nuclear envelope
disappears.
• Synapsis occurs.
– Homologous pairs of
chromosomes closely align
allowing exchange of
chromosome segments
 Metaphase I
• Aligned pairs of
replicated
chromosomes move to
the equator of the
dividing cell.
 Anaphase I
• Members of homologous
pairs of chromosomes
separate from each
other
• They move to opposite
poles of the cell.
– Chromosomes experience
independent assortment.
 Telophase I
• Chromosomes cluster at
opposite poles of cell and
begin to decondense
• Nuclear envelope may
reform.
• Cytokinesis occurs
• Interkinesis: phase between
meiosis I and and II.
• Daughter cells now haploid.
 Prophase II
• Partially unraveled
chromosomes
condense again.
 Metaphase II
• Chromosomes move to
cell equator.
• No longer homologous
pairs, so chromosomes
line up singly in middle
of cell.
 Anaphase II
• Centromeres divide and
chromosomes separate.
• Move to opposite poles
of the cell.
 Telophase II
• Clustered chromosomes
at cell pole begin to
decondense.
• Nuclear membrane
develops.
• Cytokinesis occurs.
• Produces four non-
identical haploid cells.
Mitosis & Meiosis
 Cell Cycle
• Repetitive sequence of events that characterizes life of cell.

• Consists of two main phases:

– Interphase
• Period that cells are in when not dividing.
• 90% of cell cycle
– M phase
• Includes mitosis and cytokinesis
 Cell Cycle
• Interphase has three subphases
– G1 (first gap)
• Cell makes copies of organelles and grows larger
– S (synthesis)
• Genetic material is copied
• End of this phase, cells chromosomes are doubled
– Copies are attached; thus total number of chromosomes
remains the same
– G2 (second gap)
• Cell prepares upcoming M phase
 Regulation of Cell Cycle
• Cell cycle must be regulated or can result in
cancer
– Uncontrolled cell growth
• Metastasize: cell breaks free from original cancerous
mass and resides in new area in the body
 Regulation of Cell Cycle
• Two checkpoints
– First between G1 and S
– Second between G2 and M
• To pass checkpoints, cell
must possess appropriate
amount of protein in
cytoplasm.
– These proteins activate other
proteins necessary for
production of genetic
material and mitosis
 Regulation of Cell Cycle
• To pass checkpoints, cell must possess
appropriate amount of regulating protein in
cytoplasm.
– When regulator concentration is high, cell cycle
progresses.
– When low, cell cycle is suspended at that stage.

• External and internal regulatory agents also

influence passage through checkpoints.
Why So Some Genetic Traits Tend to Travel
Together?
• Chromosomes contain genes
– Chromosomes follow law of independent assortment, not genes
• If two genes are on the same chromosome,
– the two genes are inherited together or are said to be linked or in
linkage groups
– Linkage explains why certain characteristics are frequently inherited
together, e.g. genes for hair color and eye color are linked
– What other human traits seem to occur together? Do you think they
might be controlled by linked genes?
Why So Some Genetic Traits Tend to Travel
Together? Sex-linked genes
• Example: sex linkage
• Sex chromosomes
– Contain other genes
aside from those to
determine gender.
• Example: eye color and
gender in fruit flies

• Linkage map for the

human X chromosome
 Chromosomes Can Exchange Segments
During Meiosis
• Crossing over
– Exchange of genetic
material between
chromatids of
homologous
chromosomes.
– Occurs at the chiasmata.
 Chromosomes Can Exchange Segments During Meiosis

• Crossing over
– Important mechanism
for creating new
combinations of genes.
– Disrupts linkage groups.

Crossover between homologous

chromosomes: Crossover occurs
between non-sister chromatids of
homologous chromosomes. The result
is an exchange of genetic material
between homologous chromosomes.
What Is the Chemical Nature of the Gene?

• 1860s
– Frederich Meisner studied fundamental
constituents of life
• Discovered unknown substance contains carbon,
nitrogen, oxygen, and phosphorus.
• Found it came from nucleus of cell.
• Named it nucelin
– His students renamed substance nucleic acid after
finding it was acidic.
What Is the Chemical Nature of the Gene?

• 1881
– Discovered nucleic acids were contained in
chromatin.
• Question: Was the genetic material made of
proteins or nucleic acids????
 DNA is the Genetic Material
• 1928
– Fred Griffiths, medical officer for British Ministry
of Health
• Studied the bacteria pneumoncoccus
– Two kinds
» Smooth: Virulent form that appears smooth and shiny
when grown on agar plate
» Rough: harmless form that appears rough when grown
on agar plate.
• Experimented by injecting the two types in mice.
 DNA is the Genetic Material
• Griffiths identified the material as the
transforming principle
• Avery, MacLeod and McCartney
– Study transforming principle for 20 years.
– They determined that the transforming agent was
DNA.
 DNA is the Genetic Material
• Alfred Hershey and Martha Chase
– Studied viruses that infect bacteria
• Viruses are called bacteriophages
 DNA is the Genetic Material
• Viruses are made of
• Protein coat and nucleic acid
• Viruses mix their genes with host genes
– hijack cell machinery and use it to produces new
viruses
– Usually kills host cell
 DNA is the Genetic Material
• Hershey and Chase labeled protein and DNA
differently with isotopes
– Variants of elements that share same chemical properties
but differ in number of neutrons
• Label DNA with 32P and protein with 35S
Why genetics is so
important?
Genetic conditions

Sometimes an intellectual disability is

caused by abnormal genes inherited from
parents, errors when genes combine, or
other reasons. Examples of genetic
conditions are Down syndrome, Fragile X
syndrome, and phenylketonuria (PKU).
Information capacity
Where is the genetic information
stored?
Some organelles have their own
distinct DNA
Information storage
Nucleic acids as information carriers
 Nucleosides vs Nucleotides
Nucleosides have a nitrogenous base and a five-
carbon carbohydrate group, usually a ribose
molecule.
Nucleotides are simply a nucleoside with one or
more phosphate groups attached.
The resulting molecule is found in ribonucleic
acid or RNA.
Clinical and laboratory uses of
modified nucleosides
Polynucleotides
 Conformations of DNA

http://www.bch.cuhk.edu.hk/vr_biomolecules/different-form-of-dna.html
Environmental effects of DNA
conformation
Comparisons of DNA conformers
Complementarities of nucleotides in
DNA
Supercoiling can occur in different directions
Stability of Polynucleotide backbone
Denaturant agents can cause DNA
strands to separate
Introns and exons
Eukaryotic genes do not overlap, while prokaryotic
genes are overlapped.

Splicing mechanisms occur in eukaryotes.

Most prokaryotic DNAs have overlapping genes