LECTURE 5: THE CHEMICAL BASIS OF HEREDITY

A. THE CONCEPT OF THE GENE

Ronald A. Fisher – quantitative geneticist, who aptly put forward in 1930 that the
gene could be regarded from two viewpoints:
1. As a hypothetical entity by which one could explain the results of breeding
experiments.
2. As a chemical compound of molecule.
B. THE CHEMICAL COMPOSITION OF THE CHROMOSOME
 Chromosome are the carriers of genetic material.
 Chemical components of the chromosomes: nucleic acids, protein and lipids.
Nucleic Acids – DNA AND RNA
Proteins- basic proteins: Histones or protamine / Non-histone chromosomal
proteins (generally acid proteins)
Lipids
C. DNA AS THE GENETIC MATERIAL
Herman Joseph Muller (1922) – considering a molecule to be the genetic
material, he pointed out that it should have the following characteristics: (see
page 82)
 Studies have shown that the genetic materials of the chromosome are not
lipid and protein but the DNA. (see page 82)
Frederick Griffith (1928) – reported the first work on transformation using the
bacterium diplococcus pneumpniae.
Two major forms of this organism:
1. The virulent (S) type, which forms smooth and shiny colonies on account of
the polysaccharide capsule of the cell.
2. The avirulent, rough (R) type, which is without capsules and therefore forms
rough and dull-surfaced colonies.
Oswald Avery, Colin MacLeod and Maclyn MacCarty (1944)
 Reported the successful repetition of Griffith’s work in vitro.
 Isolate and identify the transforming substance.
 Tested fractions of the heat-killed cells for transforming ability.
 Negative results were obtained only with fractions containing polysaccharide
capsule, cell protein or RNA.
 Extract containing DNA exhibited transformation, thus providing that DNA was
the genetic marerial.
Norton Zinder and Joshua Liderberg (1952) – results of transduction in
salmonella typhimurium further proved that the DNA was the genetic material. In
transduction, the bacterium-infecting virus served as the vector transferring DNA
from one bacterial cell to another.
 Bacteriophage – virus infecting bacteria where the DNA is enclosed by a protein
coat.
The RNA content of the tobacco mosaic virus (TMV), not the protein
envelope, was shown to cause infection.
D. CHEMICAL COMPOSITION OF DNA
James D. Watson and Francis H.C Crick - propose the molecular structure of
DNA. This molecular structure showed how the gene could carry out its varied
activities.
The DNA is a polymer composed of repeating nucleotides.
Each nucleotides consists of:
1. Phosphate group
2. Nucleoside
 2-deoxy-Dribose
 Nitrogenous bases
a. Purines – Adenine & Guanine
b. Pyrimidine – thymine & Cytosine

E. MOLECULAR STRUCTURE OF DNA

 The organization of the DNA chain as a linear sequence of nucleotides
(primary structure) is one aspect of the molecular structure. The molecular
structure of the DNA was proposed by Watson and Crick IN 1953. They also
proposed the double helix structure for DNA.

F. ORGANIZATION OF DNA IN CHROMOSOMES

1. Prokaryotic Chromosomes
 The e. coli circular DNA molecule is also its only chromosome 20 A^0 in
diameter and about 10^7 A^0 long.
 The DNA molecule cannot exist as along chain in the cell. Rather it must be in
a much more condensed state known as nucleod.
 Nucleod - it is formed by having the DNA molecule folded into a number of
loops held in place by RNA molecule.
2. Eukaryotic Chromosomes
 The DNA is only one of the components of the eukaryotic chromosome.
 The DNA molecule in the eukaryotes is generally much larger than the
bacterial DNA.
 Nucleosome – is the basic structural unit of the eukaryotic chromosome. It is
composed of an octamer and DNA.
 Solenoid – helical coil that is formed by stabilizing the association of the
nucleosome.
G. Replication or Synthesis of DNA
1. Mode of DNA Replication
1.1 Conservative Mode – parental molecule is fully conserved and the
daughter molecules are composed wholly of newly synthesized
molecules.
1.2 Dispersive Mode – when the parental molecule is degraded into its
component nucleotides and becomes part of the newly synthesized
daughter molecules.
1.3 Semi-conservative Mode – each daughter molecule is composed of one
conserved strand from the parental molecule and one newly synthesized
complementary strand.
 Matthew Meselson And Franklin Stahl – presented the experimental
evidence to the semi-conservative mode of replication in 1958.
 John Cairns (1963) – developed a technique of isolating E. Coli
chromosomes and labelling them with radioactive thymidine.
2. Process of DNA Replication
DNA replication or synthesis will require the following:
2.1 Parental or Template DNA – functions as the master copy upon which
the synthesis of daughter DNA molecules occurs.
2.2 Deoxyribonucleotide triphosphates (dATP, dGTP, dTTP, dCTP) –
Function as substrates.
2.3 DNA Helicase (Helix-unwinding protein) – is responsible for the
unwinding of the parental strands to create two template strands.
2.4 Single-strand DNA binding proteins (SSBP) - is responsible for
preventing the separated parental strands from re-annealing. This is
accomplished by binding of SSBP to the single-stranded DNA at the
replication fork.
2.5 DNA topoisomerase or DNA Gyrase – functions in relaxing the tension
of supercoiled twists created in unwinding the parental double helix
without rotation. This is done by breaking a phosphodiester bond in one of
the parental strands ahead of the replication fork.
2.6 DNA polymerase III or DNA Replicase – catalyzes the synthesis of
daughter DNA. It is a multimeric enzyme with a molecular mass about
900,000 daltons in its holoenzyme or complete form.
2.7 Primase – initiates the synthesis of RNA primer strands. RNA primer is
composed of 10-60 nucleotides.
2.8 DNA polymerase I which has 5’ – 3’ (primer renewal) and 3’-5’ (proof
reading) exonucleases activity cleaves the RNA primer from the
elongating DNA strands.
2.9 DNA Ligase – is joining enzyme catalyzing the formation of a covalent
phosphodiester bond between adjacent nucleotides that have been
separated by a nick (absence of covalent bond between a 3’ –OH end
and a 5’-PO4 end).
*DNA double-helix serves as the template as the template for DNA synthesis.
Replication fork – is formed when the double-helix unwinds and separates to
create two single-stranded templates.
Leading Strand – two growing strands synthesized continuously.
Lagging Strand – is antiparallel, synthesized discontinuously.
Okazaki Fragments – short RNA strand, which in turn primes the synthesis
of DNA fragments.
DNA Polymerase III – synthesizes complementing portion of the lagging
strand, still following the 5’-3’ direction.
Nick – absence of phosphodiester bond. It will be closed by DNA Ligase
which creates a covalent phosphodiester bond between a 3’-OH end and 5’-
PO4 end.
Replisome – is the complete replication apparatus moving along the DNA
molecule at the replication fork. It is composed of the holoenzyme DNA
polymerase III.
Primosome – composed of DNA helicase and DNA primase.
Prokaryotic DNA Polymerase and their functions:
DNA Polymerase I
 Removal of nucleotides during DNA repair (5’-3’ exonuclease).
 Synthesis of DNA during repair.
 Synthesis of short gaps in DNA.
 Primer removal (3’-5’ exonuclease)
 Proofreading (3’-5’ exonuclease)

DNA Polymerase II
 Syntheis of DNA during repair.
 Proofreading (3’-5’ exonuclease)

DNA Polymerase III

 DNA synthesis
 Proofreading (5’-3’ exonuclease)

DNA Polymerase IV and V

 Replication of damaged DNA.
 Eukaryotic DNA Polymerases and their Functions
Pol I
 Synthesis of lagging strand
 Primer synthesis
Pol II
 Synthesis of DNA during repair
 Proofreading (3’-5’ exonuclease)

Pol III
 Synthesis of leading strand
 Proofreading (3’-5’ exonucleases)

Mitochondrial DNA Polymerase

 Mitochondrial DNA synthesis
 Proofreading (3’-5’ exonuclease)

3. Conformations of DNA Replication

 The process involved in DNA replication would be the same in all organisms.
 Conformation of DNA replication may vary depending on the form they exist
in nature as well as the type of life cycle of the organisms.
Three General Conformations of DNA Replication
3.1 Linear DNA Replication – along the length of the linear DNA molecules
are specific points where DNA replication is initiated. This is done by the
formation of replication bubbles.
3.2 Circular DNA: Theta conformation – specific replication forks on the
circular DNA are identified. Replication is initiated by the formation of a
replication bubble at this point as replication proceeds toward both
directions around the chromosome, the replication bubbles grows in size.
3.3 Circular DNA: Rolling Circle Conformation – the rolling circle, is the
model for the replication of the single stranded DNA viruses. The whole
process can be divided into three main stages with reference to the viral
life cycle.
3.3.1 Conversion of the viral DNA to a circular duplex called a
replicative form molecule. Sometimes called single-stranded
(SS) to RF synthesis. It involves the synthesis of the
complementary strand in a reaction that require no phage-specific
proteins.
 3.3.2 The next stage is RF to RF synthesis. It begins when the phage
–encoded protein breaks the RF molecule at a specific positionon
its strand.
3.3.3 The third stage of replication ( RF to SS synthesis) occurs at later
time in infection when synthesis of (-) strands on the displaced (+)
strand is blocked by viral proteins that encapsidate the (+) strand.

BIOSYNTHESIS OF PRIMER MOLECULES

 Synthesis from single-stranded circular phage DNA templates to RF requires
de novo initiation of DNA synthesis
 Priming - an event that allows subsequent DNA elongation.

DNA Elongation after Priming

Elongation occurs once a primer is synthesized in a single-stranded cicular
phage DNA or any single stranded DNA.

H. Error Correction in DNA Replication

 The precision in DNA replication is best appreciated when one considers the
frequency of error during replication.
 In Prokaryotes, DNA synthesis rate is at 1000 nucleotides per second.
Expect the error every 277.8 hours (11.6 days0 – 2,777.8 hours (115.7 days).
 In Eukaryotes, DNA Synthesis rate is at 100 nucleotides per second, one
error should be expected every 2,777.8 hours ( 115.7days) to 27.777.8 hours
(1,157.4 days)
 High fidelity in DNA replication has been attributed to the specificity of
hydrogen bonding between the template base and the complementary base
of the incoming deoxyribunucleoside triphosphate.

Factors Responsible for DNA Replication

1. The proofreading function of the DNA polymerases
 The DNA polymerases possess 3’-5’ exonucleolytic activity.
2. Repair Mechanism
2.1 Repair of thymine dimers – thymine dimerization can be induced
between adjacent thymine bases in a DNA strand by ultraviolet light.
2.2 N-glycosidase activity – N-glycosidase hydrolysis the bond linking a
damaged base to deoxyribose in the backbone of the DNA strand.

I. RNA as the Genetic Material

 RNA seems to have a genetic role in some viruses. (ex. Tobacco
mosaic virus)
 The role of RNA in the genetic system is as intermediate between DNA
and gene expression.
  Distinctive features: special ribose sugar and the substitution of the
pyrimidine base, uracil, for thymine.
 There is no equality between the purine and pyrimidine ratios
indicating the absence of double helix.
 Maintain a single-stranded structure.
 Its stability seems to be aided by its ability to fall back on itself.

LECTURE 6. GENE FUNCTION: PROTEINS AND ENZYMES

A. Genetic Control of Proteins
1. Gene-enzyme relationship: inborn errors of metabolism.
 The function of a gene is to control/influence the phenotype.
Archibald Garrod
 English physician, first suggested the specific connection between genes and
enzymes when he studied the disease alcaptonuria in 1902.
 He established the fact that alcaptunurics excreted homogentisic acid or
alcapton, an intermediate product in a metabolic pathway.
*inherited diseases are “inborn errors of metabolism” where a person can’t make
an enzyme.
Alcaptonuria – inherited as a Mendelian recessive, urine blackening upon
exposure to air and causes arthritis.

2. One Gene-one Enzyme hypothesis

George w. Beadle and Edward L. Tatum – formulated the one-gene one
enzyme hypothesis in 1042. They stated that every gene controls a particular
enzyme and that the ultimate product of a metabolic process was affected by a
stepwise succession of enzymes, each produced by a particular gene.
Auxotroph mutants of Neurospora-crasaa – namely: pab, pdx and thi , these
mutants requires supplements of p-aminobenzoic acid, pyridoxine and thiamine.
 * subsequent studies modified this hypothesis to one-gene one enzyme
polypeptide hypothesis.
3. Protein Structure
 enzymes are proteins and their specificity is directly attributable to their
protein structure.
Proteins – are large molecules consisting of amino acids connected by peptide
linkages. May consist of one or more polypeptide chains.
Primary Structure – refers to the number and sequence of amino acids that
constitute it.
Secondary structure – is the configuration imposed upon the protein by the
peptide linkages which takes the form of a screw-like alpha helix.
Tertiary structure – the alpha helix bends and folds at various places to produce
a new configuration.
Quaternary structure – when the protein consist of two or more polypeptides. It
is the overall configuration of the protein resulting from the specific association of
its component polypeptides.
i. Rapid destruction of sickle cells
Anemia results in:
a. Over-activity of the bone marrow – increase in amount of bone marrow
(tower skull)
b. Weakness and lassitude
c. Impaired mental function
d. Poor physical development
e. Dilation of the heart – heart failure
ii. Clumping of cells and interference with blood circulation
Local failure in blood supply results in:
a. Heart damage – heart failure
b. Lung damage – pneumonia
c. Muscle and joints damage – rheumatism
d. Brain damage – paralysis
e. Gastrointestinal tract damage – abdominal pain
f. Kidney – kidney failure
iii. Collection of sickle cells in the spleen, resulting in the enlargement,
then fibrosis of the spleen
 Not all amino acids substitutions in protein lead to acute diseases.

4. Colinearity of DNA and Protein

1958 – Crick proposed that the DNA determined the amino acids sequence in
a polypeptide.
  Both the gene and polypeptide are linear structures
 The gene (DNA) is the sequence of nucleotides and the polypeptide of
amino acids
Two consequences of this relationship are:
a. A linear sequence of nucleotides should determine a specific amino acid
b. A mutational change in a particular position of the nucleotide sequence
should produce a change in a corresponding linear position in the amino acid
sequence.

Colinear – the position where the nucleotide and amino acid sequences
should be. A genetic map of nucleotide changes should correspond with a
mutational map of amino acid changes.
Charles Yanofsky et. al (1964) – provided proofs to the colinearity of the
gene and the polypeptide using tryptophan synthetase mutants of E. coli.
They observed that each mutations produced an alteration in one or any other
amino acid in the sequence in normal polypeptide A.

B. Protein Syntehsis
 The DNA is not directly involved in the protein synthesis.
 Cell continues to synthesize proteins even after its nucleus have been
removed.
 RNA synthesis is immediately affected by the loss of DNA in the cell.
 Cells that actively synthesize proteins have corresponding high RNA
content, while their DNA content would be the same as those cells that do
not synthesize protein.
 The major RNA amount of high proteins-producing cells is found in the
cytoplasm specifically in the ribosome – the site of protein synthesis.
Central Dogma of Molecular Biology – details the flow of informationin
biological systems.
The flow of information may be classified as:
1. General transfers or those that can happen in all cells :
 DNA makes DNA (replication)
 RNA (transcription); RNA make Protein (translation)
2. Special transfers or those that may happen in some cells under special
circumstances:
 RNA makes RNA (replication in viruses whose genetic material is RNA
eg. TMV)
 DNA (reverse transcription, which occurs only in animal cells infected
by certain single-stranded RNA viruses)
 DNA makes protein (DNA translation was observed in vitro in the
laboratory).
1. General transfers – happens in the cell
1.1 DNA replication (DNA-DNA) – during semi-conservative DNA
replication information is transferred from DNA to DNA.
1.2 Transcription (DNA-RNA) – RNA synthesis is the transcription
process where the transfer of information is from a double-
stranded DNA molecule to a single-stranded RNA molecule.
RNA Polymerase- an enzyme that polymerized the single-
stranded RNA from ribonucleic triphosphate on only one of the
strands of DNA as the template.
Double helix – is unwound only near the point of RNA synthesis
to provide a template strand, which is read in the direction 3’-5’.
Single RNA Polymerase – carries out all transcription in most
prokaryotes.

In eukaryotes there are three RNA Polymerases:

RNA Polymerase I – transcribe the larger rRNA genes.
RNA Polymerase II – transcribe genes that code for mRNA.
RNA Polymerase III – transcribe tRNA genes and genes that
code for other small RNAs, including the small rRNAs.

1.2.1 Messenger RNA (mRNA) – single stranded molecule

composed of nucleotides, the size ranging from 300 to
12,000 nucleotide with high molecular weight.
1.2.2 Transfer RNA (tRNA) – a molecule consisting of 75-80
nucleotides, with a molecular weight of 2.5 x 104. Has
“clover leaf tertiary” structure.
Amino acid arm – unpaired bases A-C-C at the 3’ end.
Anticodon arm – three unpaired bases in the loop that is
diametrically opposite the amino acid.
Anticodon – where the unpaired bases in the anticodon arm
constitute.

1.2.3 Ribosomal RNA (rRNA) - most RNA of the cytoplasm are

rRNA. 3 kinds may be distinguished, light (5S), medium
(16S) and heavy (23S). Each kind is single-stranded, but
some folding occurs because of hydrogen bonding between
complementary bases, giving the molecule an irregular
structure.
1.2.4 Other RNAs – in eukaryotic nuclei other kind of RNA are
observed. Some are precursor tRNA and some are
precursor rRNA.
1.3 Translation (RNA_Protein) - after transcription, the different
RNAs enter the cytoplasm where the translation process takes
place.
1.3.1 Amino acid activation – amino acids to be used for protein
synthesis are first activated.
Amino acyl synthetase – is an enzyme that exist in specific
form of each kind of amino acid and that amino acid
corresponding tRNA.
1.3.2 Polypeptide chain initiator – the first a.a = tRNA to enter
the polypeptif=de synthesis is formyl-methionone transfer
RNA.
Initiator – prevents the peptide bonding at its amino end,
therefore makes it the “lead off” amino acid.
1.3.3 Positioning of mRNA – mRNA is tangled because of
internal hydrogen bonding; except a long one short stretch
located near the 5’ end.
1.3.4 Binding of aa = tRNA – two binding sites are established in
the 70 S ribosome complex.
Amino-acyl-site (A-site of Acceptor Site) - a binding site
that receives a.a = tRNA from the cytoplasm and binds it in
position for complementary base pairing with the
corresponding codon of bound mRNA.
Tranferase – a binding enzyme which derives its energy
from conversion of GTP to GDP.
1.3.5 Peptide bond formation - Peptidyl site (P-site or Donor
site)- is shared between two ribosomal subunits and is
bound on the 30 S side by mRNA.
Peptidyl tranferase – enzyme that catalyze the formation of
a peptide bond between the carboxyl groups of the amino
acid residue.
1.3.6 Chain Elongation – codon by codon translation occurs as
the mRNA moves across the ribosome codon by codon.
1.3.7 Chain Termination – the translation process continues as
long as there are a.a. = tRNAs that are complementary to
the successive codons of the mRNA as the latter moves
across the ribosome.
Terminator codons – activate one or more protein release
factors.
Protein release factors – release the terminal amino acids
residue of the polypeptide chain.
Polycistronic mRNA – some mRNA molecules are good for
only one polypeptide chain while others are messages for
several.
 Polyribosome or Polysome – a single-strand of mRNA is
seen associated with many ribosomes forming cluster.
1.3.8 The ribosomal cycle – cycling of ribosomal subunits occurs
during translation.
2. Special Transfers
2.1 RNA Replication (RNA-RNA) – exhibited by viruses whose
genetic material is RNA.
2.2 Reverse Transcription (RNA-DNA) – is observed in animal cells
infected by certain RNA viruses that could cause tumor on their
host organisms.
Reverse transcriptase – enzyme which uses the single-stranded
viral RNA as template for the synthesis of complementary single
stranded DNA.
2.3 DNA Translation (DNA-Protein) – occurred in vitro in laboratory
experiments by introducing antibiotics.

3. Interrupted Genes – in 1977 interrupted genes where discovered

when the structure of the eukaryotic DNA and the corresponding
messenger RNA where compared.the mRNA always included a
nucleotide sequence that corresponded exactly with the polypeptide
product according to the rules of genetic code.
3.1 Exons – Are coding genes and regions represented in the mRNA.
3.2 Introms – are noncoding genes and missing from the mRNA or
intervening sequence.
RNA Splicing – is a process where the introns must first be
removed.
Spliceosome – is composed of snRNA and proteins, remove the
introns.
5’ capping – a 5’ guanine with a methyl group is attached to the
5’ end by the enzyme guananyl transferase. The cap protects
the RNA molrcule from degradation at the 5’ end.

C. The Genetic Code

1. The triplet code – the genetic codes represented each of the 20 standard
amino acids by nucleotide triplet codon. This was proved in the experiments
of Crick, Barnett, Brenner and Watts-tobin in 1961, with T4 phage mutants.
Nirenberg and Ochoa’s repective groups tried synthetic ribunucleotides
containing mixed bases in determining the general code of the other amino
acids.
1.1 The code contains many synonyms in that almost all amino acids are
represented by more than one codon. The code therefore is degenerate.
 Crick 1961 – explained the degeneracy of the code in his Wobble
Hypothesis.
Wobble Hypothesis – the first two positions of the triplet codon on
mRNA pair precisely with the first two nucleotides on the anticodon of
tRNA, but pairing at the third position may be “wobbly”.
Stop or Termination codon – UAG, UAA, UGA.
2. Universality of the Genetic Code
Von Ehrenstein and Lipmann’s experiment in hemoglobin synthesis
indicated that the code was universal (1961).

D. Genomics and Proteomics

Genomics – molecular analysis of the entire genome of species.
The two main type of genomic research:
1. Structural genomics – direct analysis of the DNA itself.
2. Functional genomics – studying the expression of a genome which genes are
turned on and off in different cells.
Proteomics – the systematics study of the amounts, modifications, interactions,
localization, and functions of all or subsets of all proteins in biological systems at
the whole organism, tissue, cellular and subcellular levels.
E. Regulation of Gene Action
 Genetic information transfer is best illustrated by Central Dogma of
Molecular Biology.
1. Regulation of Gene Action in Prokaryotes
 In prokaryotes, related genes are generally clustered and theses are
transcribed by RNA polymerase as a single, multigenic (polycistronic)
mRNA.
 Two types of Transcriptional Control System
1. Negative Transcriptional control system – regulatory genes
product binds to inhibit transcription. ( the regulatory codes for a
repressor protein)
2. Positive Transcriptional Control System – regulatory genes
codes for an expressor protein, one necessary for the gene to be
expressed.
Definition of Terms:
a. CONSTITUTIVE ENZYMES –synthesize at constants rates and in constant
amounts, regardless of the metabolic states of the cell.
b. Inducible enzymes – normally present on trace amounts but their concentration
can quickly increase a thousand folds or more when their substrate is present in
the medium, particularly when the substrates is the only carbon source of the
cell.
c. Coordinate induction – induction of a group of related enzymes or proteins.
d. Coordinate repression- repression of a group of enzymes catalyzing a
sequence of consecutive biosynthetic reactions. Coordinate repression is
ordinarily evoked by the end product of the series of biosynthetic reaction
catalyze by the repressed enzymes called end product repression.
e. Catabolite repression – enzyme repression signaled by the increase in
intracellular level of glucose.
f. Structural gene – genes that carries the message for the amino acid sequence
of a specific proteins.
g. Regulatory gene – codes for the amino acid sequences of a specific protein
called repressor; this gene determines whether or not the structural gene will be
transcribed.
h. Operator or o locus – the site in the DNA to which the repressor molecule
binds.
i. Promoter (p) – site in the DNA in which the DNA directed RNA polymerase
recognizes as an initiation signal to indicate where transcription of mRNA begins.
j. Repressor – specific protein coded for by the regulatory gene.
k. Co-repressor – small molecule that binds the aporepressore to activate the
aporepressor.
l. Inducer – small molecule that stimulates synthesis of specific proteins by binding
repressor to form repressor-inducer complex incapable of binding the o locus.
m. Operon – group of functionally related structural genes mapping
n. Negative control – inducer binds to the repressor, thereby rendering it unable to
bind to positive activator gene.
o. Positive control – inducer binds to the repressor and imparts to it the ability to
bind to the positive activator gene.
p. Positive activator gene – binding sites for the regulatory protein known as an
activator.
 1.2. Negative transcriptional control – characterized by the production of a
repressor protein by the regulatory gene.
1.2.1 Lactose operon (lac operon) – an inducible negative
transcriptional control system (the lac operon is the example of a
negative inducible system).
1.2.2 Tryptophan Operon: A repressible negative transcriptional
control system – is controlled negatively by the trp regulatory
gene.
Attenuator region – region of mRNA leader near gene E where
transcription usually terminates in the absences of regulatory input.
1.3. Positive Transcriptional Control System - the regulatory gene products
stimulates transcription; it is an expressor rather than a repressor of
transcription.
1.3.1 The Arabinose Operon: An Inducible Positive Transcriptional
Control System – it specifies the enzyme that catalyze the conversion of
l-arabinose to D-xylulose.

2. Regulation of gene action in eukaryotes

2.1 The Davidson-Britten model (1979) of gene regulation in
eukaryotes – the eukaryotic genome contains a large number of
sensors, which recognize various molecular signaling agents.
 Sensor gene regulates the activity of integrator gene which can be
transcribed only when the site is activated, the sensor site are
recognized by agents like hormones and proteins.
 Integrator gene is comparable to the regulator gene and is
responsible for synthesis of an activator RNA that may activates the
Receptor gene.
 Receptor gene is comparable to the operator gene of Lac operon
model, the receptor gene is present adjacent to each producer gene, it
signals to producer gene to synthesize mRNA.
 Producer gene is comparable to the structural gene of Lac operon
model and it synthesize mRNA for protein synthesis.

2.2 Control of Specific Gene expression by hormones

 Hormones play an important role in the regulation of gene action in
higher plants and animals. Each hormones only affects each target
tissues, which are differentiated to receive the hormone’s signals.
 Inside the cell the, hormone binds to specific cytoplasmic receptor,
which is then further processed in a form R’, enabling the H-R’
complex to cross the nuclear membrane.
  In the nucleus, the H-R’ complex is bound to a non-histone
chromosomal protein acceptor at the PO4 groups them aided by
specific phosporylating kinase enzyme.

LECTURE 7: DEVELOPMENTAL GENETICS

Developmental genetics – field that studies the relationships between gene regulation
and cell differentiation during development.
Phenoclones – inherit a stable regulatory differentiation state, as well as a genotype, at
mitosis.
A. Differential gene action: The basis of Cell Differentiation
 Immediately after fertilization, the single-celled zygote will undergo
embryogenesis (development of embryo)
Stages in the formation of different cell types
 Determination – a cell makes an irreversible commitment to follow a
specific developmental path.
 Differentiation – the expression of cell’s specialized role.
 The initial cytoplasmic environment in the embryo is set by the
Maternal Genome.
 Hox genes (homeotic genes) - provides information for anterior and
prosterior…
 Cellular Metabolism – the sum of all chemical and physical processes
which living organized substance is produced and maintained.
Steps in Cellular Metabolism
1. Pre-transcriptional Control – differential replication of certain genes or gene
amplification may result in larger amounts of gene products of genes which
have been amplified.
- Gene Amplification – a cellular process characterized by the production of
copies of a gene or genes to amplify the phenotype that the gene confers on
the cell.
- Condensation – refers to the process of compacting DNA molecules in Vitro
or in Vivo.
- Decondensation – is the process of loosening DNA molecules.
- If the chromatin is highly condensed, it is inactive while if it is decondense, it
is active.
- Euchromatin - is an active chromatin. That state of chromatin in which it
stains slightly, it is considered to be partially or fully uncoiled.
 - Heterochromatin – that state of chromatin in which it is dark staining,
genetically active, and tightly coiled.
- Cytosine – pyrimidine base occurring in plants and animals cell, usually
condensed with ribose or deoxyribose to form the nucleosides. Major
constituents of Nucleic acids.
- Highly methylated DNA is inactive while less methylated DNA is active.

2. Transcriptional Control – DNA transcription may be selectively regulated within

the nucleus through altering the relative rate of synthesis or by the differential
degradation of RNA.
- DNA Transcription is a process that involves transcribing genetic information
from DNA to RNA.
- TATA Boxes – initiation point for transcription process.
3. Translational Control – the rate of protein synthesis in sea urchin was observed
to fluctuate during the course of development.
- It could be dependent in the stability of mRNA. The longer the half-life of the
mRNA, the loner is the time it can be used during translation. The longer the
poly A, the longer the mRNA can exist.
4. Post translational Modification –is the step in the protein biosynthesis are
created by ribosome translating mRNA into polypeptide chains.
Modification may be produced in a variety of ways, such as:
a. Deletion of the part of the peptide chain
b. Changes in the state of oxidation or reduction affecting the structure of the
enzyme.
c. Attachment of small molecular moiety of the enzyme itself.
d. Polymerization and combination with phosphate groups, as in glycogen
phosphorylase.

B. Nucleoplasmic Interaction – cell differentiation based upon the differential

activation of genes.
Cleaving egg – where some destabilizing force must be introduce to set in
motion the train of sequential changes.
Blastomere – is a type of cell produced by cleavage of the zygote after
fertilization and is an essential part of blastula formation.
Cytoplasm – heterozygous mixture of substances organized into many specific
structures.
1. Molecular Exchanges between nucleus and cytoplasm
- A shuttling of information rich protein molecules back and forth between the
nucleus and cytoplasm has been demonstrated on amoeba proteus.
- Goldstein showed that some intact proteins left a radioactive nucleus
migrated into the cytoplasm but then returned either to the original
transplanted nucleus or to the host nucleus.
 2. Control of micromolecular synthesis in the nucleus by cytoplasm
- The dependence of nuclear functions on the nature of the cytoplasm has
been demonstrated in many experiments and in normal events in call
differentiation in certain organisms.

C. Genes and Morphogenesis

1. Gene effects on systems of embryonic induction
The genes may affect the integration of the developmental pattern through:
a. The tissue inducers
b. The tissue that is being induced

Sd – Segregation Disorder, “cheats” during meiosis or gametogenesis and

thus is present in more than half of the functional gametes.

2. Gene effects on endocrine systems

- Best illustrated by the pituitary dwarfism in mice.
3. Genes effects on Migrating Cells
- Genes also affects the differentiation in particular regions of whole cells that
later migrates to other regions where they become part of, or where they
affect the characteristics of other tissues.
4. Gene effects on the regulation of growth and metabolism
The genes affects the regulation of growth and metabolism in two ways:
a. Modifying a metabolic process of direct importance to the whole
organisms
b. Affecting a metabolic process to some degree, there affecting the
characteristics of a particular region at a particular time, thus changing the
growth of this region relative to the other parts of individual.