The Chemical Basis

of Heredity
Yvonne Hazel M. Fortun

MScied-Biology 1
 Please identify and
name the following: Centromere
Histones

Telomere

Sugar Phosphate Backbone

denine
uanine
Nucleotides
ystoine
hymine

Illustration from Al-khafaji, H. K., & Qader, N. N. (2014). Motif discovery and Wheel of Names
data mining in bioinformatics, 13(1), 4082-4086. DOI:10.24297/ijct.v13i1.2932
Let’s Review

Wheel of Names
Let’s Review
What are the three types of Ribonucleic Acids?

Messenger RNA
1. ___________________ Transfer RNA
2. ______________________ Ribosomal RNA
3. ____________________

Wheel of Names
 Let’s Review
5’ Capping
1._______________________

What are the three

process involve in
the pre-mRNA
before proceeding to Polyadenylation
2._______________________

translation?
Splicing
3._______________

Wheel of Names
What we know…
Gene
• A segment of DNA.
• It is a genetic factor (region of
DNA) that helps determine a
characteristic.
• It codes for specific protein and
RNA
• Composed of Deoxyribonucleic
acid, with a combination of four
different nucleotide bases.
Deoxyribonucleic acid
• A double helix strand which is the • Chromosomes are thread-like
fundamental unit of genetic
material.
• DNA contains the instructions
needed for an organism to develop,
survive and reproduce. 
• Made up of sugar-phosphate
backbone and nitrogenous bases
( Adenine, Thymine, Cytosine and
Guanine).
Chromosome
structures located inside the
nucleus of animal and plant cells.
• Transmission and expression of
genetic information.
• Made of protein called histones
and a molecule of
deoxyribonucleic acid (DNA).
What is the relationship between
Chromosomes, DNA and Genes?

Wheel of Names
 The Link Between
Chromosomes, DNA, and
Genes

• Chromosomes carry DNA in cells.

• DNA is responsible for building and
maintaining your human structure.
• Genes are segments of your DNA, which
give you physical characteristics
The Concept of Gene
 1909, Discovery: The Word Gene is Coined
• Danish botanist Wilhelm Johannsen

• Greek word genos, meaning "birth“.

• Genes were coined to describe the

fundamental physical and functional
units of heredity.

• Later Johannsen also coined the

terms “phenotype” and “genotype”.
 Concept of Genes
Classical Concept Modern Concept
Differences Similarities Differences
• Mendelian genetics (1800’s) • Studies how genes pass information
• Solely expressed based on the from parent to offspring on the basis of
phenotypes. molecular chemistry (1950 to present).
• Two important branches of
• Did not analyze the molecules • Allows the direct investigation of
Genetics.
responsible for inheritance. genotypes together with phenotypes.
• Both concepts look at the
• Heredity is particulate and the • Studies the function and behavior of
heredity.
inheritance patterns of traits can be nucleic acids and genes.
• Classical Genetics provides
explained through simple rules and
basis for Modern Genetics.
ratios.
What is a Gene?
• A unit of genetic
information that
controls a specific
aspect of the
phenotype.
• The gene is the unit of
genetic information
that specifies the
synthesis of one
polypeptide.
Gene Theory

It was proposed by Thomas Hunt

Morgan in 1911
• Won a Nobel Prize
• Chromosomes contain heredity units
and each chromosomes carries
hundreds of thousands of genes.
• The genes are arranged on the
chromosomes in the linear order and
on the special regions of locus.
 Duchenne Muscular Dystrophy

• First recognized in 1852

• Benjamin A. Duchenne in
1861.
• Fata disease that strikes
nearly 1 in 3500 males.
 Duchenne Muscular
Dystrophy

• Muscular dystrophies are a

group of genetic disorders
characterized by muscle
weakness
• X-linked recessive
inheritance.
Duchenne Muscular Dystrophy

Louis M. Kunkel
 “Gene as a set of
nucleotides that specifies
the amino acid sequence in
proteins.”

Archibald Garrod
 Concept of Colinearity

“There is a direct
correspondence between
the nucleotide sequence of
DNA and the amino acid
sequence of a protein”

Francis Crick
Is the coding sequence in a gene always
continuous in both prokaryotes and
eukaryotes?
The experiment led to the
discovery of the coding
and noncoding regions in
the eukaryotic genes.
Gene Structure
 Gene Structure

Exons (vertical rectangles)

Introns (black line)
Gene Structure
Gene Structure
 Four Major Types of Introns
Type of Intron Location Type of Splicing

Group I Some rRNA gene Self-splicing

Group II Protein-encoding genes Self-splicing

in mitochondria and
chloroplasts
Nuclear pre-mRNA Protein-encoding genes Spliceosomal
in the nucleus.

tRNA tRNA genes Enzymatic

Four Major Types of Introns
 General Characteristics of Splicing

1. The splicing of all pre-mRNA introns takes

place in the nucleus and is probably
required for RNA to move to the
cytoplasm.
2. The order of exons in DNA is usually
maintained in the spliced RNA — the
coding sequences of a gene may be split
up, but they are not usually jumbled up.
How does the presence of introns affect our
concept of a gene?
 Concepts

Gene as a set of nucleotides

Gene is an inherited factor that specifies the amino
Gene is a DNA sequence
that determined a trait. acid sequence in proteins. that encodes for an RNA
 RNA Molecules and RNA Processing
Types of RNA

Messenger RNA Transfer RNA Ribosomal RNA

The Structure of Messenger RNA

Structure for Prokaryotes

Structure for Eukaryotes

 Pre-mRNA Processing
Take note!
Prokaryotes Eukaryotes
• Transcription and • Transcription and
Translation take place Translation are
simultaneously. separated.

• Transcription and • Transcription

Translation occur in occur inside the
the Cytoplasm nucleus.
• Translation occur
mostly in the
cytoplasm.
• Ribosomes attach to • Ribosomes bind to
the Shine-Dalgarno. a modified 5’ end
of mRNA.
What are these processes?
 1. The Addition of
the 5’ Cap

The process is called

Capping at the 5’ end.
Three Capping enzymes
1. Methyl Transferase
2. Triphosphatase
3. Guanylyltransferase
Step 1. The growing mRNA Curls up placing the 5’ end to a
proximal direction near the capping complex.
Step 2. The Triphosphatase chops off one Phosphate group.
Step 3. The Guanylyltranseferase transfers the guanine
to the end of the RNA at the 5’ end.
Step 4. The methyl transferase transfers the methyl group at the
7th position of the guanine.
 Significance of Capping

1. Exonuclease protection

2.Translation promotion.
Significance of Capping

3.Nuclear export regulation

2. The Addition of
the Poly(A) Tail
 2. The Addition of the Poly(A) Tail
Polyadenylation
 Step 1: Determining the
cleavage site.

• Consensus Sequence (AAUAAA)

-upstream of the cleavage site
-determines the point at which
cleavage site will occur.
• U-rich sequence is the downstream of
the cleavage site.

Step 2: Binding of several

proteins to the upstream
and downstream cleavage site.

• CPSF
• CstF
• 2 CF
• PAP
 Step 3: The pre-mRNA is
cleaved and degradation
of the cleaved 3’.

• CstF and the CF also degraded

Step 4: Addition of adenine

nucleotides.

• CPSF and PAP adds the new

Adenine nucleotides
 Step 5: Binding of a poly
(A)-binding protein.

• PABII increases the rate of

polyadenylation.
 Significance of Polyadenylation

1. Poly(A) tail increase

stability on many mRNA.

2.Improve nuclear export.

 Significance of Polyadenylation

3. Improves the translation

process
Are there instances that some Eukaryotic
mRNA’s lack a Poly (A) tail?
• Formation of hairpin
structure
• Presence of U7
snRNA
 3. RNA Splicing
• Removal of introns in
the pre-mRNA.
• Occurs in the nucleus.
Click below to see videos
of the 3 processes.
mRNA 5’ capping and
Polyadenylation

RNA Splicing

Overall mRNA Process

Structures Needed for Splicing

• 5’ splice site
• 3’ splice site
• Branch point
• Spliceosome
Process of splicing
 Process of splicing

• Formation of
Lariat.
• Transesterification
• RNA splicing takes place in the
nucleus and must occur before
the RNA can move into the
cytoplasm.
Self-splicing
Introns
Self-splicing
Introns
 2 Alternative Process Pathways
General Idea: The same pre-mRNA can be spliced in
different ways to yield different proteins from the same gene.

1. Alternative splicing 2. Multiple 3’ cleavage sites

Purpose: To increase the diversity Purpose: To allow pre-mRNA to be

of mRNAs expressed from the cleaved and polyadenylated at
genome. different sites that can produce
mRNA’s with different lengths.
2 Alternative Process Pathways
 RNA Editing
General Idea: It is a molecular process by which protein-
coding gene change its message.

1. Site Specific Deamination 2. Guide RNA dependent U

-Converts Cytidine to Uridine. insertion
- This leads to frameshift
Site Specific Deamination Example
Site Specific Deamination Example
Guide RNA dependent
U insertion
Guide RNA dependent U insertion
Guide RNA dependent U insertion
 Function of
tRNA
• Serves as a link between
the genetic code in mRNA
and the amino acids that
make up a protein.
• Helps decode mRNA
sequence into a protein
chain.
• Capable of attaching to
only one type of amino
acid.
The Structure of Transfer RNA
The Structure of Transfer RNA
Function of rRNA
• It serves to convert the
instructions found in
messenger RNA into the
chains of amino-acids
that make up proteins.
• The catalytic activity of
the ribosomes creates a
chemical bond between
two amino acids known
as “peptide bonds’.
The Structure of the Ribosomal RNA

• Large Subunit
• Small Subunit
• Aminoacyl site
• Peptidyl site
• Exit site
• mRNA binding site
 Overview of the translation process

• Protein synthesis
• mRNA translation
 Summary of the Concept of Gene
• Wilhelm Johannsen coined the word gene.

• Classical genetics provides basis for Modern genetics.

• The concept of collinearity led to the discovery of the coding known as exons and non-coding regions
known as introns in genes.

• There are four major types of introns known as Group I, Group II, Nuclear pre-mRNA and tRNA.

• With the discovery of introns it affect the definition of the gene which is now defined as a DNA sequence that
encodes for an RNA.

• There are three RNA molecules namely messenger RNA, transfer RNA and ribosomal RNA.

• There are three process before the pre-mRNA can proceed to translation process. (5’ capping, Addition of the Poly(A)
Tail and mRNA splicing.
The Chemical Composition
of Chromosome
What is a Chromosome?

• Threadlike structures
made of protein and a
single molecule of DNA.
• Serve to carry the genomic
information from cell to
cell.
• Can be found in the
nucleus of a cell.
The Discovery of Chromosomes

• Karl Wilhelm von Nägeli observed the rod

shape in the plants and called transitory
cytoblasts.
• Walther Flemming was the first person to Karl Nageli
observed mitosis and the chromosomal
movement in detail.
• Heinrich Wilhelm Gottfried Waldeyer
coined the word “Chromosome”. Walther Flemming
-Chromo means color and Soma means
body.

Wilhelm Waldeyer
 The Prokaryotic vs Eukaryotic Chromosome
Prokaryote Eukaryote
Circular DNA molecule Linear DNA molecule
Naked- no associated proteins Associated with Histone proteins
Plasmids often present No plasmids
One Chromosome only Two or more different Chromosomes
Understanding How DNA is Packaged in a Cell
Understanding How DNA is Packaged in a Cell
Understanding How DNA is Packaged in a Cell
Understanding How DNA is Packaged in a Cell
Covalent post-translational modification
Chromatin Structure
Heterochromatin vs Euchromatin
Heterochromatin Euchromatin
Tightly packed form of DNA in the Loosely packed form of DNA in the
chromosome. chromosome.

Darkly stained Lightly stained

Found at the periphery of the
nucleus in eukaryotic cells only,
Show little to no transcriptional
activity
Found in the inner body of the
nucleus of prokaryotic and
eukaryotic cells.
Actively participate in the process of
transcription

Compactly coiled Loosely coiled

Genetically inactive Genetically active
Phenotype remains unchanged of Variation may be seen due to the
an organism affect in DNA during the genetic
process
 Centromere
Function
• Essential for equal
chromosome segregation.
• Responsible for the proper
movement of chromosomes
in mitosis and meiosis.
• Centromeric sequences are
the binding sites for proteins
that function as the
kinetochore to attach the
spindle fibers.
 Centromere Structure

• Centromeric Chromatin
• Inner kinetochore
• Outer kinetochore
• Pericentric
Heterochromatin
• Chromosome arms
-p arm and q arm
Telomere Function

• Serve as a cap that stabilizes

the chromosome.
• Prevents the chromosome
from degradation.
• Has the means to replicate
the ends of the chromosome.
 Telomeric Sequences
• Usually consist of a series
of cytosine nucleotides
followed by several
adenine or thymine
nucleotides or both.
• The length varies from
chromosome to
chromosome and from a
cell to cell.
 Telomere
Structure

• Lagging Strand-
longer strand.
• Leading Strand-
shorter strand.
Telomere Structure
Why is the lagging strand longer than the leading strand?
Cell Death
Telomere in relation to Aging and Cancer
 Telomerase Enzyme

• A helper protein responsible for

reverse transcriptase to convert
RNA to DNA.
 Summary of the Chemical Composition of Chromosomes
• Chromosomes are threadlike structures made of protein and a single molecule of DNA that can carry the
genomic information from cell to cell.
• Walther Flemming was the first person to observed mitosis and the chromosomal movement in detail.
• Heinrich Wilhelm Gottfried Waldeyer coined the word “Chromosome”.
-Chromo means color and Soma means body.
• Prokaryotic chromosome has a circular DNA molecule and Eukaryotic chromosome has a linear DNA
molecule.
• The DNA molecule is supercoiled and wrapped around 8 histone proteins in order to fit inside the
nucleus.
• Heterochromatin are tightly packed form of DNA while the Euchromatin are loosely packed form of
DNA in the chromosomes.
• Centromere is an important structure in the chromosome that is serve as the foundation of the
kinetochores which the spindle fibers will attach and segregate the sister chromatids.
• Telomere serve as a cap to stabilize the chromosome and prevent it from degradation.
DNA as a Genetic Material
 Characteristics of
Genetic Material
• Genetic material must contain
complex information
• Genetic material must Replicate
faithfully
• Genetic material must encode
phenotype.
DNA as the source of Genetic
Information:
The discovery of the transforming
principle
• DNA was responsible for phenomenon
called: Transformation.
• In 1928, he was the first person to
observed the bacterial transformation in
which the form and function of a
bacterium changes, when he attempt to
develop a vaccine against pneumonia.

Fred Griffith
DNA as the source of Genetic Information: Oswald Avery
The Identification of the transforming principle

• They succeeded in isolating and

purifying the transforming substance.
• In 1944, they published their discovery Colin Macleod
that the transforming principle was DNA
in “Studies on the Chemical Nature of
the Substance Inducing Transformation
of Pneumococcal Types,” in the Journal
of Experimental Medicine.
Maclyn McCarty
DNA as the source of Genetic Information:
The Hershey-Chase experiment Alfred Hershey

• They used radioactive forms (isotopes) of

phosphorus and sulfur
• They showed that only the DNA of a virus
needs to enter a bacterium to infect it. Which
led that their experiment providing strong
support for the idea that genes are made of
DNA. They firmly restated the conclusion that Martha Chase
Avery, et al. had more tentatively proposed in
1944.
Early Studies of DNA
Johann Friedrich Miescher
• Swiss physician and biologist.
• He experimented and isolated a new
molecule - nuclein - from the cell nucleus.
• He determined that nuclein was made up
of hydrogen, oxygen, nitrogen and
phosphorus and there was an unique ratio
of phosphorus to nitrogen.
• The substance was later renamed nucleic
acid by one of his students.
 Albrecht
Kossel
• He won a Nobel Prize in Physiology or
Medicine in 1910.
• He began to investigate the chemical
compositions and properties of nucleic
acids.
• Between 1885 and 1901, he discovered
that these acids were composed of five
nitrogen bases: adenine, cytosine,
guanine, thymine, and uracil.
Phoebus Aaron Levene
• He is an organic chemist in the
early 1900’s.
• He discovered that DNA consists
of a large number of linked,
repeating units, each containing
a sugar, a phosphate, and a base
(together forming a nucleotide).
• He is perhaps best known for his
incorrect tetranucleotide theory
of DNA.
Erwin Chargaff and his colleagues
• He is an Austrian Biochemist.
• They found that DNA from different
organisms varies greatly in base
composition.
• Their findings disproved the
tetranucleotide theory.
• They discovered that in DNA, the ratios of
adenine (A) to thymine (T) and guanine (G)
to cytosine (C) are equal.
• Now known as the Chargaff’s rule.
Watson and Crick’s Discovery of
the 3-Dimensional Structure

• In 1953, James Watson and Francis Crick

discovered the three-dimensional
structure of DNA.
• Chargaff’s Rule was the key in solving the
3 dimensional structure of DNA.
• Won a Nobel Prize in 1962.
 RNA as a genetic material

• Frankel-Conrat and B. Singer (1957) Heinz- Fraenkel-Conrat

performed an experiment with tobacco
mosaic virus (TMV) and demonstrated
that in some cases RNA acts as a
genetic material. Tobacco mosaic virus
(TMV) does not contain any DNA. It
consists of RNA surrounded by a hollow
cylinder of protein subunits.
Bea Singer
 Summary for the DNA as a Genetic Material

• There are three characteristics of a genetic material, it must contain complex information, must
replicate faithfully and must encode phenotype.
• The discovery of transforming principle by Griffith, Avery, Macleod and McCarty proved that genes
are made up of DNA.
• The Hershey-Chase experiment provided a strong support for the idea that genes are made of
DNA.
• Johann Friedrich Miescher determined that nuclein was made up of hydrogen, oxygen, nitrogen and
phosphorus and there was an unique ratio of phosphorus to nitrogen.
• Albrecht Kossel discovered the five nitrogenous bases in the DNA.
• Phoebus Levene best known for his incorrect tetranucleotide theory of DNA.
• Chargaff’s rule states that in DNA, the ratios of adenine (A) to thymine (T) and guanine (G) to
cytosine (C) are equal.
• In 1953, James Watson and Francis Crick discovered the three-dimensional structure of DNA with the
help of existing information especially the Chargaff’s rule.
• Frankel-Conrat and B. Singer’s experiment demonstrated that in some cases RNA acts as a
genetic material.
Chemical Composition
of DNA
 Primary Structure of DNA

• The primary structure of DNA

consists of a string of nucleotides.
Each nucleotide consists of the
following:
• a five carbon sugar.
• A nitrogen- containing base.
• a phosphate
Primary Structure of DNA

• There are two types of

nitrogen-containing
bases:
• 1. Purines (adenine and
guanine)
• 2. Pyrimidines
(thymine, uracil and
cytosine).
• Attached to the 1’-
carbon atom of the
pentose sugar.
 Primary Structure of DNA

• Phosphate group consists of a phosphorus atom bonded to four oxygen atoms.

• Carries a negative charge, which makes DNA acidic.
• Phosphate always bonded to the 5 carbon atom of the sugar in a nucleotide through the help of
phosphodiester bond.
Polynucleotide Strands

• Made up of many nucleotides

linked by covalent bonds
known as the Phosphodiester
linkages which attached the
• 5-phosphate group of one
nucleotide to the 3-carbon
atom of the next nucleotide.
Secondary Structure of
DNA
• It is the three dimensional
configuration known as its
fundamental helical structure.
• The two polynucleotide strands run
in opposite directions—they are
antiparallel, which means that the 5
end of one strand is opposite the 3
end of the second.
• Hydrogen bonds link the bases on
opposite strands.
Different Secondary Structures
• B-DNA form, exists when plenty of
water surrounds the molecule and
there is no unusual base sequence
in the DNA—conditions that are
likely to be present in cells.
• A-DNA form, exists when less
water is present. It is shorter and
wider.
• Z-DNA form, the sugar–phosphate
backbones zigzag back and forth.
Different Secondary Structures
 Special Structures in DNA and RNA

• In DNA and RNA, base pairing between

nucleotides on the same strand produces special
secondary structures such as hairpins and
cruciforms.
• Hairpins form when sequences of nucleotides
on the same strand are inverted complements
 Special Structures in DNA and RNA

• In double stranded DNA, sequences that are

inverted replicas of each other are called
inverted repeats.

• An inverted repeat that is complementary to

itself is called palindrome.

• Cruciform is formed from an inverted repeat when a hairpin

forms within each of the two single-stranded sequences.
 DNA Methylation
• Addition of methyl groups (-CH3) to certain
positions on the nucleotide bases.
• Most DNA methylation is essential for
normal development.
• It plays a very important role in a including
genomic imprinting, X-chromosome
inactivation, and suppression of repetitive
element transcription and transposition.
• DNA methylation in different genomic
regions may exert different influences on
gene activities based on the underlying
genetic sequence.
 Bends in DNA
• A series of four or more adenine –
thymine base pairs—cause the DNA
double helix to bend.
• The DNA helix can also be made to
bend by the binding of proteins to
specific DNA sequences.
• One example is the SRY protein,
which is encoded by a Y-linked gene
and is responsible for sex
determination in mammals.
 Venn Diagram for DNA and RNA
Deoxyribonucleic Acid Ribonucleic Acid
Differences Differences
Similarities
• Single stranded
• Double stranded
• Ribose(More oxygen atoms)
• Deoxyribose (Fewer oxygen atoms)
• Modified 5’ cap and 3’ poly-A tail.
• Structured into Chromosomes.
• Uses Adenine, Cytosine • Uses uracil
• Uses thymine
and Guanine • Stores information about protein structure
• Stores genetic information
• Has sugar and phosphate • Read by ribosomes
• Read by polymerases
backbone. • Can’t self replicate but it can have multiple
• Can self replicate via DNA replication
structures (mRNA, tRNA, rRNA)
• Can last for a long time
• Doesn’t last for a long time
• Read from 3’ to 5’
• Formed from 5’ to 3’
 Summary for the Chemical Composition of DNA
• The primary structure of DNA consists of a five carbon sugar, nitrogen- containing base, and a phosphate.
• There are two types of nitrogen-containing bases namely, Purines (adenine and guanine) and
Pyrimidines (thymine, uracil and cytosine).
• Phosphate always bonded to the 5 carbon atom of the sugar in a nucleotide through the help of
phosphodiester bond.
• Secondary Structure of DNA is the three dimensional configuration known as the helical structure.
• Hydrogen bonds link the bases on opposite strands.
• Hairpins are another secondary structure that forms when sequences of nucleotides on the same strand
are inverted complements.
• Cruciform is a secondary structrethat formed from an inverted repeat when a hairpin forms within each
of the two single-stranded sequences.
• The primary structure of DNA can be modified by addition of methyl groups (-CH3) to certain positions on
the nucleotide bases.
• Bending affects how the DNA binds to certain proteins and may be important in controlling the
transcription of some genes.
References
• Pierce, Benjamin A. , Genetics: A Conceptual Approach
• Cold Spring Harbor Laboratory DNA learning Center Resources
• National Genome Research Institute
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containing gigantic introns in a unique gene expression program
during Drosophila spermatogenesis. Plos Genetics,
https://doi.org/10.1371/journal.pgen.1008028
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10.3390/genes12081272
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• https://resources.quizalize.com/view/youtube/prokaryotic-vs-eukaryotic-chr
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• https://www.gistsupport.org/resources/cells-cancer-and-more/how-dna-is-p
ackaged-in-a-cell/

• https://www.nature.com/scitable/topicpage/dna-packaging-nucleosomes-a
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.
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