MODX WEEK 1: INTRODUCTION TO

MOLECULAR BIOLOGY AND DIAGNOSTIC

MOLECULAR BIOLOGY

 Branch of biology that studies the

molecular basis of biological activity.

 Study of biochemical nature of the

genetic material and its control
phenotype.

 Study of biochemical mechanism of

inheritance.

HISTORY

 1953: James Dewey Watson and Francis

Harry Compton Crick proposed the
double helical mode of DNA based on
the study of Maurice Wilkins and
Rosalinda Franklin

 1957: Meselson and Stahl confirmed the

Watson and Cricks semiconservative
THE CELL
model of DNA replication
 Coined as the basic unit of all organism.
 1958: F.H.C Crick proposed the central
dogma of molecular biology.  It is the structural and functional unit of
all life
CENTRAL DOGMA
Composed of 4 significant element

1. Hydrogen
2. Carbon
3. Oxygen
4. Nitrogen

HISTORICAL NOTES

 Robert Hook: Discovered the cell. He

referred to it as a small empty chambers
in the structure of cork.

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  Matthias Schleiden and Theodore
Schwan: Concluded that all plants and
animal tissue are composed of the cell.
 Rudolf Virchow: Proposed the theory of
Biogenesis where cell only arise from
preexisting cell.
TWO TYPES OF THE CELL
EUKARYOTIC CELL
STRUCTURE AND FUNCTION
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PROKARYOTIC CELL
 Known to be the most abundant
organism on earth
 Each prokaryotic cell is surrounded
by membrane bound plasma
 The cell has no subcellular
organelles, only folding of the
plasma called mesosomes.
 DNA is condensed within cytosol to
form the nucleoids.
 Some prokaryotes have tail like
flagella for movement.
 In eukaryotes, cells aggregates to form
tissues or organ and these are further
organized to form whole organism.
PLASMA MEMBRANE
STRUCTURE:
 Phospholipid bilayer containing lipids
and proteins and some carbohydrates;
forms a selective permeable boundary
of the cell.
FUNCTION:
 Acts as a physical barrier to enclose cell
contents.
  Regulates material movement into and  Extensive interconnected membrane
out of the cell. network that varies in shape; Ribosomes
attached on the cytoplasmic surfaces
 Functions in cell communication
 Ribosomes are involved in the protein
NUCLEUS synthesis.

STRUCTURE: FUNCTION:

 It is enclosed within a double membrane  Modifies, transport, and stores protein

called nuclear envelope; contains the produced by attached ribosomes.
nucleolus.
B. Smooth Endoplasmic Reticulum:
o Nucleolus: It consist of RNA and protein
STRUCTURE:
which function in ribosomal unit
assembly  Extensive interconnected membrane
network lacking ribosomes
o Nucleoplasm: It surrounds the
Chromatin and the nucleoli FUNCTION:
Function:  Synthesizes, transport and stores lipids.
 It contains the DNA that serves as the  Detoxifies drugs.
genetic material for directing protein
synthesis.  Forms vesicles and peroxisomes.

CYTOPLASM GOLGI APPARATUS

STRUCTURE: STRUCTURE:

 Can be seen between the plasma  Series of several elongated, flattened

membrane and the nucleus where the
other cellular elements are embedded.
 Organelles are membrane-bound
structure which carry out specific
metabolic activities of the cell.
 Cytosol provides support for organelles
and serves as the viscous fluid medium
FUNCTION:
 It is responsible for various cellular
process
 Dissolve solute and move materials
around.
ENDOPLASMIC RETICULUM
A. Rough Endoplasmic Reticulum:
STRUCTURE:
saclike membranous structures.
FUNCTION:
 Modifies, packages, and sort materials
that arrive from the endoplasmic
reticulum in transport vesicles.
MITOCHONDRIA
STRUCTURE:
 Double-membrane bound organelles
containing a circular strand of DNA.
o Outer membrane: Highly permeable
to small molecule due to the
presence of pore-forming protein
called porin.
o Intermembrane: Contains many
protein that participate in oxidative
phosphorylation.

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 o Inner membrane: Has. Multiple o Microtubules: Provides structural
folds projecting in-wards, called support.
cristae.
CELL MEMBRANE TRANSPORT
FUNCTION:
 Refers to the movement of particles
 It is responsible for the production of across or through a membranous
energy in the form of ATP barrier.

LYSOSOMES  The movement of compound across this

STRUCTURE:
 Spherical shaped membrane bound
organelles formed from the Golgi
apparatus; contains digestive enzyme.
PASSIVE TRANSPORT PROCESS:
 The fluid inside the lysosomes is much
more acidic, it is about 8.4, than the
normal ph of about 7.0-7.3
FUNCTION
 Digest microbes or material by the cell
PEROXISOMES
STRUCTURE:
and other intracellular membranes
depends on the chemistry of molecule
often requires specialized transport
mechanism.
 Diffusion is the movement of a
substance from higher concentration to
an are of its lower concentration
 Simple diffusion: dissolves solute
through the plasma membrane
 Facilitated Diffusion: Requires a protein
carrier

 Small vesicle surrounded by a  Osmosis: It is the diffusion of water

membrane.
FUNCTION:
 Involved in the biosynthesis
cholesterol (peroxidase enzymes)
CYTOSKELETON:
STRUCTURE:
Organized network of protein filament.
FUNCTION:
 Maintains the integral structural support
and organization of the cell.
o Microfilaments: maintains cell shape.
o Intermediate filaments: give
mechanical support to structures like
nucleus and plasma membrane
point across a selectively permeable
membrane.
ACTIVE TRANSPORT PROCESS:
of
 This type of cell membrane transport
uses energy (ATP) provided by the cell.
o exocytosis: refers bulk movement of
substance out of the cell by fusion of
secretory vesicle with the plasma
membrane
o Endocytosis: Refers to bulk movement
of substance into the cells by vesicles
forming at the plasma membrane.

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W1 TOPIC: INTRODUCTION TO CYTOGENETICS (diseased condition accounting for the
appearance of newborns with congenital
HISTORY
disorders or deformities)
 8000 and 1000 B.C
- could be altered in individuals before
o Domestication of horses,
they were passed on to offspring (how
camels, oxen & various breeds
newborns could “inherit” traits that their
of dogs
parents had “acquired” because of their
 5000 B.C. environment)
o Cultivation of maize, wheat, rice
- Aristotle
• Golden Age of Greek culture
- Studied with Plato (20 years)
oHippocratic School of Medicine
(500–400 B.C.) - Extended hippocrates idea
 On the Seed) active
- embryo developed not because it
“humors” in various
already contained the parts in
parts of the male body
miniature (as some Hippocratics had
served as the bearers of
thought) but because of the shaping
hereditary traits
power of the vital heat
 could be healthy or
diseased and can be - “vital heat”- heat produced within the
altered body
 Aristotle (384–322 B.C.)
- Sperm and eggs in mammals had not
o generative power of male
been observed not until 1800s.
semen resided in a “vital heat”
contained within it History
 capacity to produce
offspring of the same  William Harvey (1578–1657)
“form” as the parent o theory of epigenesis
 heat cooked and shaped • organism is derived
menstrual blood which from substances
was the “physical present in the egg that
substance” that gave differentiate into adult
rise to an offspring structures during
Additional notes: embryonic
development
1. -derived from the wolf family have been
domesticated, selective breeding • body organs are not
initially present in the
Hippocratic early embryo but
instead are formed de
- “humors” from male body to the semen
novo (anew)
and passed on to offspring

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 • 17th century
 “homunculus”
 sex cells contain a complete,
miniature adult, perfect in every
form
Additional notes:
 Englisg anatomist
o Wrote treatise on reproduction
and development patterned
after Aristotle’s work
History
• 1830, Matthias Schleiden & Theodor
Schwann
o cell theory (all organisms are
composed of basic units called
cells, which are derived from
similar preexisting structures
• Louis Pasteur
o disapproved spontaneous
generation
o living organisms were
considered to be derived from
preexisting organisms and to
consist of cells
o creation of living organisms
from nonliving components
• Carolus Linnaeus (1707–1778)
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 doctrine of fixity of species
 animal and plant groups have
remained unchanged in form
since the moment of their
appearance on Earth
Additional notes:
Spontaneous generation (supposed production
of living organisms from nonliving matter)
This doctrine was particularly embraced by those
who believed in special creation, including the
Swedish physician and plant taxonomist, Carolus
Linnaeus (1707–1778), who is better known for
devising the binomial system of species
classification.
History
 Charles Darwin
o The Origin of Species (1859)
o theory of natural selection
o causes of evolutionary change
 Alfred Russel Wallace
o natural selection was based on
the observation that
populations tend to consist of
more offspring than the
environment can support,
leading to a struggle for survival
among them.
Additional notes:
Alfred Russel Wallace
 Those organisms with heritable traits
that allow them to adapt to their
environment are better able to survive
and reproduce than those with less
adaptive traits. Over a long period of
time, slight but advantageous variations
will accumulate. If a population bearing
these inherited variations becomes
 reproductively isolated, a new species 2. He applied quantitative data analysis to his
may result. results and showed that traits are passed from
parents to offspring in predictable ways.
History
3. gamete formation (sperm and egg cells
 Gregor Mendel (1860)
formation); other. His work was published in
o true starting point of our
1866
understanding of genetics
5b. Chromosomes in diploid cells exist in pairs,
o conducted a decade-long series
called homologous chromosomes.
of experiments using pea plants
- members of a pair are identical in size
o concluded that each trait in the
and location of the centromere, a
plant is controlled by a pair of
structure to which spindle fibers attach
genes and that during gamete
during cell division.
formation members of a gene
pair separate from each other - mitosis and meiosis.

o forms the foundation for Mitosis

genetics, which is defined as the
o chromosomes are copied and
branch of biology concerned
distributed so that each daughter cell
with the study of heredity and
receives a diploid set of chromosomes.
variation
Meiosis
o conducted his experiments
before the structure and role of o associated with gamete formation.
chromosomes were known o Cells produced by meiosis receive only
one chromosome from each
• 20 years after his work
chromosome pair, in which case the
was published,
resulting number of chromosomes is
advances in microscopy
called the haploid (n) number. This
allowed researchers to
reduction in chromosome number is
identify chromosomes
essential if the offspring arising from the
• members of each union of two parental gametes are to
species have a maintain, over the generations, a
characteristic number constant number of chromosomes
of chromosomes called characteristic of their parents and other
the diploid number (2n) members of their species.

• Mitosis and meiosis

were discovered on the
late decades of 19th
century.

Additional notes:

1. Augustinian monk;

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 – independently proposed that
genes are carried on
chromosomes

– basis of the chromosome theory

of inheritance

• inherited traits are

controlled by genes
residing on
chromosomes faithfully
transmitted through
gametes, maintaining
genetic continuity from
generation to
generation.

Additional notes:

1. as hypothesized by Mendel

After 2, 1. genes and chromosomes

Additional notes:
o Colorized image of human male
chromosome set. Karyotype notation.
o Humans have a diploid number of 46
exist in pairs and 2. members of a
gene pair and members of a
chromosome pair separate from
each other during gamete
formation
After 3, Chromosome I of
Drosophila melanogaster (fruit fly)

History

• Walter Sutton and Theodor Boveri

– noted that genes and

chromosomes, as observed
under the microscope, have
several properties in common

– behaviour of chromosomes
during meiosis is identical to the
presumed behavior of genes
during gamete formation
described by Mendel

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Terminologies:
• Genes
– unit of heredity
– Defined as units of inheritance;
Carried on chromosomes
– Found as sections of DNA
strands which codes for a type of
protein
– DNA is the hereditary material
that is passed on from one
generation to the next
– Each cell in an organism has one
or two sets of the basic DNA
complement called a genome
• Genome
– complete set of genetic
instructions characteristic of an
organism
• Allele
– variants of genes
– alternate form of a gene. It
produces different observable
features or phenotype.
• Genotype
– alleles that are present(
underlying traits)
– set of alleles for a given trait.
The genotype of an organism is
the inherited instructions it
carries within its genetic code.
• Phenotype
– alleles that are expressed(
visible traits)
– observable feature
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• Dominant alleles
– has an effect when present in
just one copy
• Recessive alleles
– must be present in both to be
expressed
History
• Genetic variation
– Drosophila melanogaster
– variation produced by a
mutation in one of the genes
controlling eye color.
– mutations
• defined as any heritable
change
• source of all genetic
variation.
– showed that the mutant trait
could be traced to a single
chromosome, confirming the
idea that genes are carried on
chromosomes
Additional notes:
2. Allele of a gene (white eyed-mutant)
 History the nucleus and cytoplasm, many researchers
thought proteins would be shown to be the
• Chemical component of chromosomes
carriers of genetic information
– 1920s, scientists were aware
that proteins and DNA were the
major chemical components of
chromosomes

– 1928, Frederick Griffith

• discovered the
phenomenon of
transformation, dead
bacteria could transfer
genetic material to
"transform" other still-
living bacteria.

– 1944, Oswald Theodore Avery,

Collin Mcleod and Maclyn
McCarty

• published experiments
showing that DNA was
History
the carrier of genetic
information in bacteria • Structure of the DNA molecule and
mechanism by which information stored
– 1952 by Alfred Hershey and
in it is expressed to produce phenotype
Martha Chase

• Hershey-Chase
Experiment

• showed that the DNA is

the genetic material of
the viruses that infect
bacteria, providing
further evidence that
the DNA is the molecule
responsible for
inheritance.
Additional notes:
Additional notes:
Nucleotide- Building block of DNA/RNA
1920-* Of the two, proteins are the most
abundant in cells. o Sugar + nitrogen base= nucleoside

There are a large number of different proteins,

and because of their universal distribution in

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Sugar- central component; phosphate- attached
on the 5th carbon of CHO; Nirogen base- 1st
carbon of CHO
Nitrogenous bases- A(adenine), G(guanine),
T(thymine), C(cytosine)
History
• 1953, James D. Watson and Francis
Crick
Additional notes:
One of the great discoveries of the twentieth
century was made in 1953 by James Watson and
Francis Crick, who established that the two
strands of DNA are exact complements of one
another, so that the rungs of the ladder in the
double helix always consist of A “ T and G ‚ C base
pairs.

• Rosalind Franklin and Maurice Wilkins

– double-helix model

– structure showed that genetic

information exist in the
sequence of nucleotides on each
strand of DNA.

• Although the structure of the DNA

showed how inheritance works, it was
still not known how DNA influences the
behavior of cells.

– DNA controls the process of

protein production

– discovered that the cell uses

DNA as a template to create
matching messenger RNA Additional notes:

– nucleotide sequence of In nucleus with transcription,

messenger RNA 1. nucleotide sequence in one strand of
– this translation between DNA is used to construct a
nucleotide and amino acid complementary RNA sequence
sequence is known as the 2. once RNA molecule is produced, it
Genetic Code. moves to the cytoplasm.

3. In protein synthesis, the RNA—called

messenger RNA, or mRNA for short—
binds to a ribosome.

4. Synthesis of proteins under the direction

of mRNA is called translation

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 5. Proteins, the end product of many
genes, are polymers made up of amino
acid monomers.
6. There are 20 different amino acids
commonly found in proteins. How can
information contained in mRNA direct
the addition of specific amino acids into
protein chains as they are synthesized?
The information encoded in mRNA and
called the genetic code consists of a
linear series of nucleotide triplets. Each
triplet, called a codon, is complementary
to the information stored in DNA and
specifies the insertion of a specific amino
acid into a protein. Protein assembly is
accomplished with the aid of adapter
molecules called transfer RNA (tRNA).
Within the ribosome, tRNAs recognize
the information encoded in the mRNA
codons and carry the proper amino acids
for construction of the protein during
translation. As the preceding discussion
shows, DNA makes RNA, which most
often makes protein. This sequence of
events, known as the central dogma of
genetics, occurs with great specificity.
Using an alphabet of only four letters (A,
T, C, and G), genes direct the synthesis of
highly specific proteins that collectively
serve as the basis for all biological
function
Genotype to Phenotype
• Sickle-Cell Anemia
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Additional notes:
single-nucleotide change in the DNA encoding b-
globin (CTC S CAC) leads to an altered mRNA
codon (GAG S GUG) and the insertion of a
different amino acid (glu S val), producing the
altered version of the b-globin protein that is
responsible for sickle-cell anemia. (glutamic acid
to valine)
Development of Recombinant DNA
• early 1970s
• Discovery of bacteria capable of
protecting themselves from viral
infection by producing enzymes that cut
viral DNA at specific sites.
• “restriction enzymes”
– could be used to cut any
organism’s DNA at specific
nucleotide sequences,
producing a reproducible set of
fragments
– development of DNA cloning
• way of making large
numbers of copies of
DNA sequences
Additional notes:
Before 2. When cut by these enzymes, the viral
DNA cannot direct the synthesis of phage
particles.
Soon after researchers discovered that
restriction enzymes produce specific DNA
fragments, methods were developed to insert
these fragments into carrier DNA molecules
called vectors to make recombinant DNA
molecules and transfer them into bacterial cells.
As the bacterial cells reproduce, thousands of
copies, or clones, of the combined vector and
DNA fragments are produced (Figure 1–10).
These cloned copies can be recovered from the
bacterial cells, and large amounts of the cloned
DNA fragment can be isolated

Additional notes:

Biotechnology is also being used to enhance the

nutritional value of crop plants.

More than one-third of the world’s population

uses rice as a dietary staple, but most varieties of
rice contain little or no vitamin A. Vitamin A
deficiency causes more than 500,000 cases of
blindness in children each year. A genetically
engineered strain, called golden rice, has high
levels of two compounds that the body converts
to vitamin A. Golden rice should reduce the
burden of this disease. Other crops, including
wheat, corn, beans, and cassava, are also being
modified to enhance nutritional value by
increasing their vitamin and mineral content.
Additional notes:
For medical applications, researchers have
In cloning, a vector and a DNA fragment
transferred human genes into animals—so-
produced by cutting with a restriction enzyme
called transgenic animals—that as adults,
are joined to produce a recombinant DNA
produce human proteins in their milk. By
molecule. The recombinant DNA is transferred
selecting and cloning such animals,
into a bacterial cell, where it is cloned into many
biopharmaceutical companies can produce a
copies by replication of the recombinant
herd with uniformly high rates of protein
molecule and by division of the bacterial cell.
production. Human proteins from transgenic
animals are now being tested as drug treatments
for diseases such as emphysema. If successful,

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these proteins will soon be commercially produce human proteins in their milk. By
available. selecting and cloning such animals,
biopharmaceutical companies can
produce a herd with uniformly high rates
of protein production. Human proteins
from transgenic animals are now being
tested as drug treatments for diseases
such as emphysema. If successful, these
proteins will soon be commercially
available.

PICTURE AT THE END OF NOTES:

Additional notes:

Livestock such as sheep and cattle have been

commercially cloned for more than 30 years,
mainly by a method called embryo splitting. In
1996, Dolly the sheep was cloned by nuclear
transfer, a method in which the nucleus of an
adult cell is transferred into an egg that has had
its nucleus removed

Additional notes:

- first genetically altered organism to be Additional notes:

patented, the onc strain of mouse,
genetically engineered to be susceptible Genetic Studies Rely on the Use of Model
to many forms of cancer. These mice Organisms
were created for studying cancer
1st gen model organisms-mus musculus,
development and the design of new
drosophila melanogaster;
anticancer drugs.
Microbes- Saccharomyces cerevisiae, E.coli
- researchers have transferred human
genes into animals—so-called Nematode- Caenorhabditis elegans
transgenic animals—that as adults,
Dario rerio- zebra fish

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 Additional notes:

A timeline showing the development of

genetics from Gregor Mendel’s work on pea
plants to the current era of genomics and its
many applications in research, medicine, and
society. Having a sense of the history of
discovery in genetics should provide you with
a useful framework as you proceed through
this textbook.

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Additional notes:

The molecular basis for hundreds of genetic

disorders is now known (Figure 1–13). Genes for
sickle-cell anemia, cystic fibrosis, hemophilia,
muscular dystrophy, phenylketonuria, and many
other metabolic disorders have been cloned and
are used for the prenatal detection of affected
fetuses. In addition, tests are now available to
inform parents of their status as “carriers” of a
large number of inherited disorders. The
combination of genetic testing and genetic
counseling gives couples objective information
on which they can base decisions about
childbearing. At present, genetic testing is
available for several hundred inherited
disorders, and this number will grow as more
genes are identified, isolated, and cloned. The
use of genetic testing and other technologies,
including gene therapy, raises ethical concerns
that have yet to be resolved.

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