Part 4—Genetics and Molecular Biology
Much of the text material is from, “Essential Biology with
Physiology” by Neil A. Campbell, Jane B. Reece, and Eric J. Simon
(2004 and 2008). I don’t claim authorship. Other sources were
also used and are noted.
Nicholas, Alexandra, and Children
• In Mendel’s pea plants, an F 1 hybrid looked like one of the parents
because the dominant allele had the same effect on the organism’s
• In some organisms, however, F1 hybrids can express an intermediate
phenotype between those of the two parents.
• For example, when red and white snapdragons are crossed, all of the
F1 hybrids have pink flowers.
Allele = an alternative form of a gene (one member of a pair)
that is located at a specific position on a specific chromosome.
• High cholesterol, or hypercholesterolemia, is the result of a recessive
allele (we will call it “h”).
• Homozygous dominant individuals (HH) do not have the disorder.
• Heterozygous individuals (Hh)—about one in 500 people—have blood
cholesterol levels about twice normal.
• Homozygous recessive individuals (hh)—about one in a million people—
have much higher elevated cholesterol levels (about five times normal).
• Cholesterol can build-up in the arteries and lead to blockages, a condition
known as atherosclerosis.
Punnett Squares—Cholesterol Levels
Parent 1 Parent 2
h HH h
Cholesterol levels: Hh Hh
Diet and exercise can
hh also affect cholesterol
Hh—moderately high levels
H H h h H h
H HH H h hh h H Hh h
HH HH hh hh Hh Hh
HH hh Hh
• Low-density lipoproteins (LDL) are cholesterol-containing molecules
circulating in the blood.
• The H allele is responsible for the production of LDL receptors in cell
membranes that enable the cells to uptake and breakdown cholesterol.
False color electron micrograph
• The HH genotype assures a full complement of LDL receptors—LDL levels
are generally within normal limits.
• The Hh genotype has about one-half the normal number of LDL receptors,
and LDL levels are twice as high as in the HH genotype.
• The hh genotype lacks LDL receptors, allowing LDL to accumulate at very
• Cholesterol-lowering drugs, such as the statins, can be effective in treating
• In co-dominance, both alleles are expressed, such as in the AB blood
• Co-dominance is different from incomplete dominance, the expression
of an intermediate trait.
• So far we have discussed inheritance patterns involving two alleles (one
on each homologous chromosome pair).
• Multiple alleles also exist for certain phenotypes, such as the ABO blood
group in humans.
• For the ABO blood group, the human blood phenotypes are A, B, AB, and
• The letters refer to two carbohydrates (antigens), known as A and B, on
the surface of red blood cells (RBCs).
• RBCs may contain one carbohydrate (A or B), both carbohydrates (AB),
or neither (O).
Blood Type Compatibility
• Compatible blood types are critical for transfusion of blood from donor to
• If a recipient receives a foreign type (A or B), antibodies in the recipient’s
blood bind to the foreign carbohydrate, causing RBCs to clump together.
• The clumping can damage the filtration mechanisms (nephrons) in the
Incompatibility and Compatibility
The Three Alleles
• The four ABO blood types result from combinations of three alleles, IA, IB,
• IA produces carbohydrate A, IB produces carbohydrate B, and i produces
• One of each of the three possible alleles is inherited from each parent.
Combinations of Alleles
• IA and IB alleles are dominant to the i allele.
• The six combinations are:
– IA * IA and IA * i result in type A blood.
– IB * IB and IB * i result in type B blood.
– IA * IB result in type AB blood where both alleles are expressed.
– i * i result in type O blood, where neither the A nor the B carbohy-
drate is present.
Blood Type Predictor
Try calculating these combinations using your knowledge of
Mendel’s principles, Punnett squares, and the alleles, IA, IB, and i.
Blood Donor Programs
• Whole blood
• National Marrow Donor Program (http://www.marrow.org)
• So far, the examples have involved one or more genes that specify one
• In other instances, a gene can specify a number of characteristics, which
is known as pleiotropy.
• A well-known type of pleiotropy is the genetic disorder, sickle-cell disease.
• The hemoglobin molecules in red blood cells (RBCs) transport oxygen
to the body’s tissues.
• In sickle-cell disease, abnormally-shaped hemoglobin molecules are
produced in the bone marrow.
• These “sickled” RBCs have a greatly-reduced oxygen-carrying capa-
• It is a homozygous recessive disorder—the allele (ss) must be present
on both homologous chromosomes.
• In sickle-cell disease, hemoglobin molecules tend to link together and
• This is more likely to happen when blood oxygen content is low due to
high altitude, overexertion, or respiratory ailments.
• When hemoglobin crystallizes, RBCs deform to a sickle shape, leading
to a number of cascading symptoms.
Clumping of sickle d
Bre akdo of re d RBCs and clogging
sickled RBCs in the
blood cells (RBCs) of small blood
ve sse ls
Physical weakne ss l
He art faiure Sple en damage
He art faiure Pain and fe v e r
Ane mia Brain damage
Othe r organ damage
Ane mia Brain damage Othe r organ damage
Impaire d mental Impaire d mental Pneumonia and
function function othe r infections
• Sickle-cell disease kills about 100,000 people world-wide each year.
• About one in ten African Americans is heterozygous (Ss) for the gene (the
disease is rare in other ancestries).
• It is the most common inherited disorder among African Americans, affect-
ing about one in 500 newborn.
• Although no cure exists, blood transfusions and certain drugs may relieve
some of the symptoms.
• Mendel studied genetic characteristics that occur on an “either-or” basis.
• Many characteristics, such as human skin color, vary along a continuum
in the general population.
• Polygenic inheritance involves the additive effects of two or more genes
on a single phenotype characteristic.
• This is the converse of pleiotropy, where a single gene can affect several
• Say, hypothetically, skin color is completely determined by three genes,
each inherited separately.
• The dark-skin alleles (A, B, and C) each contributes one unit of darkness.
• The light-skin alleles (a, b, and c) each contributes one unit of lightness.
• Each dark-skin allele is incompletely dominant to the light-skin alleles.
Units of skin darkness:
A= B = C
Units of skin lightness:
Combinations of Alleles
• A person who has AABBCC would have very dark skin, while a person
who has aabbcc would have very light skin.
• A person who has AaBbCc would have skin of an intermediate shade.
• Because the six alleles have a simple additive effect, AaBbCc would
produce the same skin color as AABbcc.
• Sixty-four genotype combinations would be possible, resulting in seven
shades of skin color.
A Simplified Inheritance Model
P generation AABBCC x aabbcc
1 intermediate skin shade
1/64 (very light skin)
Histogram and bell- 15/64
shaped distribution of 20/64 (intermediate skin shade)
skin shades 15/64
1/64 (very dark skin)
http://fig.cox.miami.edu Total = 64/64
• Many more shades of skin color are possible than the seven depicted in
• Intermediate shades of skin color are also determined by environmental
factors such as sunlight exposure.
• Therefore, the genetic basis of skin color will not tell the entire story no
matter how well the genes are described.
Genetics and the Environment
• Many human characteristics result from the interactions of genetics and
• Some characteristics, such as eye color, are fully genetically determined.
• Other characteristics, such as height, have an environmental component
(such as diet during childhood).
• Human gender identity and sexual orientation are part of the ongoing
debate about the role of genetics versus environment, or “nature versus
• Some dominant alleles aren’t always consistently expressed.
• The probability that a person having a dominant allele will display the
associated phenotype is known as its penetrance.
• In complete penetrance, the associated phenotype is always displayed
(p = 1.00).
• In incomplete penetrance, the phenotype may or may not be shown (p
• The BRCA1 gene associated with one form of breast cancer is incom-
• About 70 percent of women with this relatively-rare, disease-causing
gene will develop breast cancer by age 70.
• The breast cancer gene is said to be 70 percent penetrant.
• Women with this gene should be screened regularly for early detection
of the disease.
• The degree to which an allele expresses a particular phenotype can
vary from individual-to-individual.
• Polydactyly is a genetic condition involving an individual having more
than ten fingers or toes.
• This condition shows variable expressivity—some persons with the
allele have additional fully-functional fingers or toes while others have
Chromosomal Basis of Inheritance
• Mendel published his research in 1866, researchers, however, were only
able to establish the genetic processes several decades later.
• They noticed parallels between chromosomes and Mendel’s inheritance
factors at the beginning of the 20th century.
• The chromosomal basis of inheritance, a major axiom in biology, emerged.
The axiom states:
1. All genes are located on the chromosomes.
2. The behavior of homologous chromosomes during meiosis
and fertilization accounts for the inheritance patterns from
parents to their offspring.
Axiom = an established rule, principle, or law.
Homologous Chromosomes, Revisited
Electron micrograph (false color image)
• Two or more genes located close together on a chromosome tend to
be inherited together.
• One notable case in Mendel’s work involved flower color and pollen
shape in pea plants.
• The F2 plants did not show the expected ratio predicted for a dihybrid
• The observed ratio is supported by examining the crossing-over pat-
terns of chromatids during meiosis I.
• “Linked genes” that cross-over together produce phenotypes that can-
not be predicted by Mendel’s principles alone.
• The fruit fly, Drosophila melanogaster, is often used in genetics research
because it can be inexpensively grown, and can produce several genera-
tions within a few months.
• The farther apart two genes are on homologous chromosomes, the more
likely they will display genetic recombination since there are more points
where crossing-over can occur.
• The results of crossing-over patterns can be used to determine the
relative location of genes on chromosomes and develop linkage maps.
• Prior to genome mapping, observation of crossing-over patterns was the
primary method for developing maps of genes residing on chromosomes.
• We briefly discussed the role of the X and Y chromosomes in sexual
differentiation as female or male.
• The X chromosome also carries genes for characteristics unrelated to
• A gene located on the X chromosome is known as a sex-linked gene.
Role of the X Chromosome
• The X chromosome, because of its larger size, has many more genes
than the Y chromosome.
• The X chromosome has sex-linked genes unrelated to sexual differen-
• The Y chromosome carries very few genes, in large part because it is so
• Experiments have been conducted with fruit flies to determine how sex-
linked genes determine the genotypes and phenotypes of their offspring.
Genes on the X Chromosome
• The X chromosome has between 900 and 1,200 genes—many of the
genes are involved in human development in both sexes.
• Only one of the genes (DAX1) is involved in female sexual differentia-
• The other genes involved in determining the female phenotype are on
the autosomal chromosomes.
Genes on the Y Chromosome
• The few genes on the Y chromosome—including the SRY gene—
are mostly involved in male sexual differentiation.
• Other genes on the Y chromosome are also involved in male sex-
ual function and fertility.
• All Y-linked traits will be expressed since the Y chromosome is
hemizygous (having only one copy of the allele passed from the
Genes on the Y Chromosome (continued)
• Hairy ears is one of a small number of Y-linked traits that is not re-
lated to sexual function— the allele is incompletely penetrant since
not all hairy-eared men sire sons with hairy ears.
• The amount of ear hair can vary from slightly- to very-hairy due to
• Some human genetic disorders are the result of recessive alleles on the
• A male need only inherit one of these sex-linked alleles from his mother,
while a female would need one from each parent, a much rarer situation.
• Thus, males are far more often afflicted by these disorders.
• Sex-linked disorders include red-green color blindness, hemophilia, and
Duchenne muscular dystrophy.
Rods and Cones
the retina of the human
Red-Green Color Blindness
• Red-green color blindness is a relatively common sex-linked disorder in
males, although the severity can vary (presumably due to expressivity).
• In some affected people, red or green hues may appear to be gray, while in
other people, confusion may exist over different shades of these colors.
• The disorder results from the malfunctioning of cones (color receptors) in
the retina of the eye.
• Although males are usually affected, a very small number of females may
have similar problems.
Ishihara Color Plate
What embedded figure do you see?
• Hemophilia is a sex-linked recessive disorder—it almost always affects
• Individuals bleed excessively when injured because of an abnormal allele
on the X chromosome for factors VII and IX that enable blood clotting.
Victoria, Queen of England
A Famous Case Study
• In the 18th century, hemophilia plagued the royal families of Europe who
were often closely related through intermarriage.
• The first royal family member who was known to have hemophilia was
the son of Queen Victoria of England.
• The allele may have occurred as a spontaneous mutation in one of the
gametes of Victoria’s mother or father, which was passed by Victoria to
Nicholas and Alexandra
• Hemophilia was introduced into the royal families of Prussia, Russia, and
Spain through the marriage of two of Victoria’s daughters, who carried the
• Queen Victoria’s granddaughter, Alexandra, was married to the last Czar
of Russia, Nicholas.
• Through an analysis of family pedigree, it was later demonstrated that
Alexandra was a carrier of the recessive gene, as were her mother and
• Alexandra and Nicholas’s son, Alexis, had hemophilia—the family met a
tragic end in the overthrow of the czar and White Russia in the early 20th
Solid-circle-within-a-circle—carrier of X-linked recessive gene.
Blue square—afflicted with hemophilia.
Molecular Biology of the Gene
Deoxyribonucleic Acid (DNA)
A Brief History of DNA
• Although DNA was known as a molecule in cells by the end of the 19th
century, biologists and geneticists did not recognize its role in heredity.
• In the 1930s, scientific attention focused on chromosomes, which were
known to carry genes.
• During the 1940s, scientists established that chromosomes consisted of
DNA and protein molecules.
• By the early 1950s, much of the scientific world was convinced that DNA
was the hereditary material for all forms of life, although the details were
• In 1953, the structure of DNA was deduced from scientific observations,
as we will discuss.
• DNA and RNA are nucleic acids consisting of long chains of monomers
known as nucleotides.
• The nucleotides are joined by covalent bonds through dehydration syn-
• The structure has a sugar-phosphate backbone in a repeating pattern of
DNA Nucleotide Structure
Thymine (T) and cytosine (C)
have single-ring structures
(known as pyrimidines).
CH2 Adenine (A) and guanine (G)
have double-ring structures
(known as purines).
Deoxyribose + phosphate group = sugar-phosphate backbone
DNA base pairing rules: A with T, and G with C in a double helix
• The nitrogenous base defines the nucleotide since all nucleotides have
identical sugar and phosphate groups.
• For DNA, the nitrogenous bases are adenine (A), cytosine (C), guanine
(G), and thymine (T).
• The bases form molecular appendages along the sugar-phosphate back-
• DNA and RNA have similar but not identical molecular structures—RNA
contains the nitrogenous base, uracil (U), instead of thymine.
Appendage = a part that is added or attached to
Discoverers of DNA’s Double Helix
and Francis Crick
• James Watson, an American, visited Cambridge University in the early-
1950s where Francis Crick was studying protein structure using a tech-
nique known as X-ray crystallography.
• They “happened” to view an x-ray crystallographic image produced by
Rosalind Franklin of King’s College that revealed the structure of DNA
as a double helix.
Rosalind Franklin’s X-ray crystallography image of DNA.
Exploration and Discovery
• The general configuration of DNA suggested that the molecule consists
of two strands of nucleotides in a double helix arrangement.
• Watson and Crick puzzled over the consistent spacing between the two
• With help from others, they concluded the four nitrogenous bases can
only be arranged in specific ways: A always pairs with T, and G always
pairs with C.
Exploration and Discovery (continued)
• A single-ring (pyrimidine) base (T or C) pairs with a double-ring (purine)
base (A or G) to maintain a consistent spacing between the two strands
in the double helix.
• Watson and Crick created a three-dimensional model of the DNA double
helix based on their inductions, with much help from Franklin, unbeknown
Inductive reasoning = reasoning from detailed facts to
• Each DNA strand serves as a molecular template to guide the reproduc-
tion of a complementary strand.
• The sequence of nucleotide bases in a strand determines the sequence
of bases in the other strand by applying the base-pairing rules (A with T
and G with C).
• If one strand has the sequence, ACTGA, then the complementary strand
has the sequence, TGACT.
Complementary = in this context, relating to the specific pairing of
nucleotides between strands of a DNA or an RNA molecule.
Complimentary = encouraging, approving, or pleasing.
• The breakage of the three hydrogen bonds between the paired nitro-
genous bases enables the two strands of DNA to unwind to allow for
• Each strand serves as a template to produce a complementary strand.
• Nucleotide molecules line-up along each template in accordance with
the base-pairing rules (A with T and G with C).
• Enzymes link the nucleotides through dehydration synthesis to form
new complementary strands.
• The two daughter DNA strands wind to form a double helix, just like the
• Although the general mechanism for DNA replication is simple in concept,
the actual process is complex, involving more than a dozen enzymes and
• Enzymes that form the covalent bonds between nucleotides are known as
• The replication process is fast, and proceeds at a rate of about 50 nucleo-
tides per second—despite the speed, replication is usually very accurate.
• DNA replication occurs at many points along the separated strands of
• These replication bubbles greatly shorten the time for replication since
DNA has billions of nucleotides.
Damage to DNA
• Polymerases and proteins are also involved in repairing damaged DNA.
• Damage can be caused by environmental sources including toxic chem-
icals and high-energy electromagnetic radiation in x-rays and ultraviolet
• UV-B radiation in sunlight, especially in large doses, can damage DNA in
10-5 nm 10-3 nm 1 nm 103 nm 106 nm 1m 103 m Wavelength
Electromagnetic Gamma X-rays Ultra- Infrared Microwaves Radio waves
radiation rays violet
Visible light (380 to 750 nm)
Sunlight is about 45 percent visible light,
46 percent infrared, and 9 percent ultraviolet.
Beyond limiting excessive exposure to
sunlight, the best protection from UV
radiation is wearing sunglasses and
protective clothing, and using a proven,
high-SPF sunscreen. http://content.answers.com
Genotype and Phenotype Revisited
• The genotype of an organism is its genetic makeup, and the pheno-
type is its physical traits.
• The molecular basis of the phenotype is the result of many proteins,
each with a specific function to perform.
• The genes in DNA do not synthesize proteins directly, but dispatch
instructions in the form of RNA.
• RNA directs the protein synthesis process within the ribosomes and
cytoplasm of cells.
• DNA and RNA, as we already discussed, are polymers synthesized from
long strings of monomers known as nucleotides.
• In DNA, the “alphabet” is A, T, G, and C—in RNA, it consists of A, U, G,
• Thus, the language of DNA and RNA are written in a linear sequence of
only four bases.
• The sequence of these bases, along with a beginning and end, make-up
DNA and RNA strands.
G = guanine
Transcription and Translation
• The processes from DNA to RNA is known as transcription, and from RNA
to proteins as translation.
• In transcription, the nitrogenous bases in DNA are rewritten as a sequence
of bases in RNA.
• In translation, the bases in RNA specify sequences of amino acids for syn-
thesizing polypeptides to form protein molecules.
• Although DNA and RNA have just four bases, they direct the synthesis of
20 amino acids.
• How can only four nucleotide bases specify the 20 amino acids found in
all known life?
• If each base uniquely coded for one amino acid, only four amino acids
would be possible.
• In actuality, the bases are read during translation as three-letter “words”
known as base triplets or codons
• Triplets allow for 43 or 64 possible combinations, more than the number
of amino acids.
• Many experiments have verified that the flow of information from DNA to
RNA, and then to protein formation, is based on codons of three bases.•
• Sixty-one of the 64 codons contain the genetic code for 20 amino acids
(some amino acids can be specified by more than one codon).
• Although redundancy exists in the genetic code, there is no ambiguity
since each codon can specify only one amino acid.
• AUG has the dual role of coding for the amino acid, methionine, and
serving as the start signal for translating the RNA instructions to form
proteins from amino acids.
• UAA, UAG, and UGA serve as stop signals in the translation process.
• Transcription from DNA to RNA occurs in the nucleus of eukaryotic cells.
• The strands of DNA separate at nodes where the transcription process
• Only one of the DNA strands serves as the template for the formation of
• Nucleotides to form an RNA strand are paired one at a time with the DNA
bases—the base pairings are A with U, T with A, G with C, and C with G.
Transcription Process (continued)
• The nucleotides in the RNA chain are linked by the transcription enzyme,
• Transcription ends when the RNA polymerase reaches the stop codon in
the DNA template.
• The single-strand of RNA is a complementary copy of the DNA template.
• RNA is spliced to remove non-coding regions (introns) while in the cell
• A cap and tail are also added.
• The resulting molecule, now known as messenger RNA or mRNA, con-
tains “exons” of genetic instructions.
• mRNA passes through the pores of the nuclear membrane for translation
in the cytoplasm.
• Transfer RNA (tRNA) serves as the interpreter for translating the codons
in mRNA into instructions for forming polypeptides (proteins) from amino
• tRNA is found in the vicinity of the ribosomes, which synthesize polypep-
• The tRNA molecule is small, consisting of about 80 nucleotides—in com-
parison, mRNA can be very long.
Translation Process (continued)
• tRNA selects the correct amino acids by “reading” the sequence of mRNA
• Ribosomes in the cytoplasm coordinate the functions of mRNA and tRNA
in synthesizing polypeptides that will be further processed to form complex
Formation of covalent bond
through dehydration synthesis
Amino acid Polypeptide
Transfer RNA amino acid
• Any change in the normal DNA nucleotide sequence is known as a mu-
• Mutations can involve large regions of a chromosome, or just a single
nucleotide pair as in sickle-cell disease.
• Mutations can involve: 1) base substitutions, 2) base insertions, or 3)
• In a base substitution, a nucleotide is replaced by another, creating a
different RNA codon—GGC for the amino acid, glycine, could become
AGC for serine.
• If the RNA codon is changed from GAA to GAG, no change would result
since both code for glutamine—this type of change is known as a silent
• Occasionally, a base substitution can lead to an improved protein—one
with new capabilities that improves the adaptation of the organism and
• More often, however, a genetic mutation can be harmful to the organism.
Base Insertions and Deletions
• Mutations involving the insertion or deletion of one or more nucleotides
in a gene can have disastrous effects.
• Adding or deleting even one nucleotide alters all subsequent codons in
the “three letter” tRNA reading frame.
• An mRNA molecule with the sequence AAG-UUU-GGC-GCA codes for
the polypeptide sequence, lysine-phenylalanine-glycine-alanine.
• If a U is deleted from the second codon (UUU), the mRNA sequence
shifts to the left, and now becomes AAG-UUG-GCG-CAU (assuming
that the last amino acid happens to be U).
• This polypeptide sequence codes for lysine-leucine-alanine-histidine.
• The protein is not likely to be functional since the polypeptide will not
have the correct configuration.
More on Mutations
• The replication, transcription, and translation processes are usually very
• Mutations occasionally have beneficial effects that produce the diversity
of genes in the living world—however, they typically have undesired con-
• Mutations occurring without known cause are called spontaneous events.
• Other sources of mutations are physical and chemical agents, which are
known as mutagens.
Sources of Mutagens
• Some chemical mutagens can produce incorrect base-pairings in DNA.
• Mutagens that cause cancer are known as carcinogens.
• These include smoking, dietary factors, and excessive exposure to UV-B
• Viruses exist in a fuzzy zone between what is considered life and non-
• A virus consists of a small amount of genetic material wrapped in a pro-
tective coat of protein.
• However, they do not have a metabolism, and are unable to reproduce
on their own.
• A virus survives by infecting a cell with its genetic material (RNA or DNA)
and directing the cell to produce more viral copies.
• The influenza (flu) virus, like many other animal viruses, has RNA as its
• Other RNA viruses cause the common cold, measles, mumps, and polio-
• Some RNA viruses affect only plants, such as the tobacco mosaic virus.
False color electron
• A RNA virus fuses with the plasma membrane of a cell, and release its
genetic material into the cytoplasm.
• The virus’s RNA serves as the template for synthesizing new strands of
• The viral strands serve as mRNA for the synthesis of new viral proteins.
• The proteins assemble themselves around the new viral RNA to provide
a protective coat.
• Numerous copies of the virus exit through the cell’s plasma membrane
to infect other cells.
• Viruses in the herpes family include chicken pox, shingles, cold sores,
herpes simplex, and genital herpes.
• These viruses have DNA, which reproduces in the host cell nucleus.
• DNA viruses obtain their envelopes from the cell’s nuclear membrane.
• Copies of DNA in the herpes virus can remain as genetic material in the
nuclei of some nerve cells (neurons)
• They remain latent until a physical stress—such as cold, sunburn, or
emotional stress—triggers the viral DNA to begin producing the virus
• Thus, a herpes viral infection can repeatedly flare-up during a lifetime.
Herpes Virus (continued)
False color electron
Recovery from a Virus
• The amount of damage from a virus depends in part on how rapidly the
immune system responds to the threat.
• The severity of damage also depends on the ability of the infected tissue
to repair itself through mitosis.
• Tissues in the respiratory tract replace cells damaged in a common cold.
• In poliomyelitis, the virus targets motor neurons, which do not divide, and
there-fore the damage is permanent.
• Motor neurons control skeletal muscles of the body including those that
in the 1950s
Rancho Los Amigos,
Antiviral Drugs and Vaccines
• Antibiotics, used for treating bacterial infections, are ineffective against
• However, antibiotics can be used to treat secondary bacterial infections
that result from a viral infection.
• Antiviral vaccines, developed using dead or attenuated virus strains, are
used to build-up the body’s immune defenses.
• Development of antiviral drugs has been slow since destroying the virus
often kills its host cells.
• Every cell in an organism started with one zygote that had gone through
many rounds of mitosis.
• Each body cell contains an identical DNA pattern because mitosis dupli-
cates the entire genome.
• During embryonic development, genes regulate how unspecialized cells
develop into different structures and functions.
• These cells are known as stem cells, and the process is known as cell-
An ovum 1-to-3 hours after sperm
penetration, just prior to the fusion of
genetic material from the mother and
• In transcription, the genes in DNA determine the nucleotide sequences in
• In translation, mRNA determines the amino acid sequences to synthesize
the polypeptides that form proteins.
• The flow of genetic information from genes to proteins—from genotype to
phenotype—is known as genetic expression.
• Cells follow different pathways to develop as different tissues during early
• These include neurons, muscle cells, blood cells, and skin cells, among
Genetic Potential of Cells
• Although different cells have different functions, they each have identical
• Every body cell has the potential to act like any other body cell if the pat-
tern of gene expression could somehow be altered.
Patterns of Gene Expression
Lens cells of the
Gene Pancreas cells Neurons
Glycolysis enzyme Active Active Active
Crystallin Inactive Active Inactive
Insulin Active Inactive Inactive
Hemoglobin Inactive Inactive Inactive
Four genes are shown in three types of cells—different
combinations of the genes are expressed.
Genetic Potential of Plant Cells
• Many types of plant cuttings can develop into mature plants because of the
genetic potential of their cells.
• A single cell removed from a carrot root and placed in a growth medium
begins dividing (through mitosis) and eventually grows into a mature plant.
• This technique is used to produce thousands of genetically-identical plants,
or vegetative clones.
• By vegetative cloning, commercial growers can propagate large numbers
of plants that have high yield or are resistant to viral diseases.
• Vegetative cloning illustrates that cellular differentiation does not lead to
irreversible changes in the DNA.
Tomato plants growing
in a hothouse
• Animal cells that do not normally regenerate body parts retain their full
• In the 1950s, the nuclei of frog eggs were replaced with nuclei from the
intestinal cells of tadpoles.
• Under strict methodological control, the embryos developed into tadpoles
and then into frogs.
Dolly, the first cloned sheep, was born in 1996.
First Mammal Cloning
• Dolly was cloned using the nucleus from an adult somatic cell inserted into
an egg cell that had its nucleus removed.
• The cell was grown in a culture medium.
• The developing embryo was then implanted into the uterus of a surrogate
• Dolly resembled her genetic parent—but not the egg donor mother or the
• Nuclear transplantation has also been used in cloning mice, cows, goats,
pigs, cats, and other animals.
• Farm animals with desirable phenotypes have been cloned to produce
complete herds with the same physical traits.
• Researchers have used cloned animals to assure genetically-identical
populations to control for extraneous variables in scientific experiments.
• Pharmaceutical companies have explored the use of cloned animals for
potential medical uses.
• Biologists have explored how cloned animals could help restock popula-
tions of endangered species.
In 2003, a baby banteng was produced
by the cloning of frozen skin cells from an
adult male that died in 1990. The nuclei
from the banteng cells were inserted into
cow eggs, and one was brought to term
by the cow.
• The goal of therapeutic cloning is to generate stem cells for producing
new body tissues.
• Stem cells in early embryonic life produce all of the differentiated cells
in the body—these cells are said to be “pluripotent.”
• Embryonic stem cells can divide seemingly indefinitely when grown in
a laboratory environment.
Embryonic Stem Cells
Eight-cell embryo Blastocyst
Pluripotent stem cells
Red blood cells
• Differentiated cells in a laboratory culture might be used for repair of
injured or diseased organs in humans.
• Embryos might be produced using cell nuclei from a human patient.
• Stem cells from these embryos could be harvested and induced to
develop entire organs that could be transplanted (but still science fic-
• The harvesting of stem cells, and other aspects of reproductive and
therapeutic cloning, are part of an ongoing debate about ethics and
Just because we are able to achieve something technologically,
is it okay to do so?
Adult Stem Cells
• Adult stem cells are partially differentiated, and therefore can only give
rise to a few types of cells.
• Stem cells in bone marrow produce many different types of blood cells.
• Although adult stem cells are more difficult to grow in a lab culture, their
medical use—if it were to become feasible—may result in less debate
than the use of embryonic tissue.
Bone marrow stem cells
(false color electron micrograph)
• The process from genes to the synthesis of functioning proteins is com-
• The process can be regulated to turn-on, turn-off, speed-up, or slow-down
the gene expression.
Lactose and Lactase
• Lactose is a disaccharide (glucose + galactose) found in dairy products.
• Lactase is an enzyme produced by the bacteria, Escherichia coli (E. coli),
in the small intestine.
• A surge of lactose occurs when milk or other dairy products are ingested.
• In response, E. coli express three genes for producing lactase and other
enzymes for the digestion and absorption of lactose.
• Once the lactose is digested, the E. coli stop producing the enzymes by
turning-off the expression of the three genes.
• The on-off mechanism is controlled by a repressor protein that blocks the
activation sites on the genes.
• DNA is densely packed with proteins in chromatin within the cell nucleus.
• The high compaction prevents gene expression since the enzymes for
transcription cannot physically come in contact with the DNA molecules.
• DNA packing is a biological process that enables the long-term inactiva-
tion of certain genes.
DNA shown in orange and proteins in blue.
• Gene regulation can also extend across cell boundaries in multicellular
• A cell can produce and secrete chemicals that regulate other (receptor)
• Genes are transcribed from DNA to RNA in the receptor cell in response
to the chemical signal.
• Cell signaling is a key mechanism in the differentiation and development
a single-cell zygote into a complex organism.
Cell Signaling (continued)
• Cell signaling is also important in the coordination of intercellular activities
in a mature organism.
• A signal molecule binds to a receptor molecule in the plasma membrane,
which activates a signal transduction pathway in the cell.
• Signal molecules include estrogen, testosterone, cortisol, and many other
Genetic Basis of Cancer
• Cancer is a collection of diseases in which cells are no longer effectively
controlled by the mechanisms that normally limit division during mitosis.
• The absence of a normal cell cycle control system is due to changes in
some genes, or possibly in the way that certain genes are expressed.
Cancerous squamous cell with cross-sectional cut
• The abnormal behavior of cancer cells was observed long before much
was known about either the cell control cycle or the role of genes in tumor
• Some viruses carry cancer-causing genes in their DNA or RNA that can be
inserted into host cells.
Oncogenes and Proto-Oncogenes
• A gene that causes a cell to be cancerous is called an oncogene or
• A normal gene that has the potential to become an oncogene is known
as a proto-oncogene.
• A proto-oncogene results from mutations that produce changes in gene
Genes and Growth Factors
• Many of the genes involved in cancer code for growth factors—proteins
that stimulate cell division in the cell control cycle.
• These proteins normally keep the rate of mitotic cell division at the right
• Uncontrolled cell growth can occur when the synthesis of these proteins
Cell control cycle G1 phase
• Other genes may inhibit rampant cell division by suppressing the division
and growth of cancerous cells.
• Tumor-suppressor genes are a focus of research as a promising cancer
A protein produced by a tumor-
suppressor gene shown
surrounding a segment of
• Almost 150,000 people in the United States were diagnosed with colon or
rectal cancer in 2003.
• Colon cancer—a well-understood type of human cancer—illustrates a key
principle of how cancer develops:
More than one mutation is usually needed to produce a
full fledged-cancer cell.
Colon Cancer Cells
False-color electron micrograph
• Colon cancer begins as an unusually-frequent mitotic division of normal-
appearing cells in the lining of the colon wall.
• Cellular changes result in DNA mutations at the initial stage, and at the
later stages too.
• The number of progressive mutations before the cancer is evident—at
least four—explains why some cancers can take a long time to develop.
• The cancerous cells are grossly altered in their physical appearance by
the time of their fourth mutation.
Progressive Mutations (continued)
Role of Heredity
• Cancer is a genetic disease (but usually not inherited) since it results from
mutations in the DNA.
• Most mutations that lead to cancer arise in the organ where the malignant
• Genetic mutations are not passed from parent to child if they do not affect
zygotes (ova or sperm cells).
• In a small number of families, the mutations in one or more genes can be
passed to their children and may predispose them to cancer.
• The cancer usually does not appear unless the person acquires additional
• One out of ten women in the United States will be diagnosed with breast
cancer in their lifetimes.
• The large majority of cases appears to have nothing to do with inherited
• A very small number of breast cancer cases, however, is related to muta-
tions in the BRCA1 gene.
• Research suggests that the protein encoded by a normal BRCA1 gene
serves as a tumor suppressor.
• Clinical tests are available for detecting the presence of mutations in the
• Unfortunately, few options currently exist if a positive test result is found.
• Cancer is the leading cause of death in most developed countries including
the United States.
• Death rates for some types of cancer have declined, but the overall rate is
on the rise.
• Cancer-causing agents—carcinogens—lead to DNA changes and cellular
• In some instances, the mutagenic effects may require years of exposure to
• Lifestyle factors have a role in at least 50 percent of all cases of cancer.
Mutagenic = something capable of causing a gene-change.
Among the known mutagens are radiation, certain chemicals and
Cancer Incidence, United States
Estimate d Estimate d
Rank Cance r en
Known or likely carcinog of factor case s de aths
1 Prostate Testosterone, possibly die tary fat 220,900 28,900
2 Breast Estroge n, possibly die tary fat 212,600 40,200
3 Lun g Tobacco smoke 171,900 157,200
4 Colon and rectum High die tary fat, low dietary fiber 147,500 57,100
5 Lymphatic system Viruses for some typ es 61,000 24,700
6 Skin Ultr aviolet light 58,800 9,800
7 Bladder Tobacco smoke 57,400 12,500
8 Uterus Estroge n 40,100 6,800
9 Kidney Tobacco smoke 31,900 11,900
10 Pancreas Tobacco smoke 30,700 30,000
11 Leukemias X-rays, b enzene, viruses for some types 30,600 21,900
12 Ovary Large number of ovulation cycles 25,400 14,300
13 Stomach Table salt, tob acco smoke 22,400 12,100
14 Mouth and throat Tobacco including smokeless tobacco; alcoho l 20,600 5,500
15 Brain / nervou s system Physical trauma, x-rays 18,300 13,100
16 Liver Alcohol, h epatitis virus 17,300 14,400
17 Cervix Viruses, tobacco smoke 12,200 4,100
All other cancers 154,500 92,000
Totals 1,334,100 556,500
Two past cultural
Healthy versus cancerous lungs
A Possible Outcome
• Some of the chemicals found in first- and second-hand tobacco smoke
are known to be potent carcinogens.
• Excessive exposure to UV light, a carcinogen, can cause skin cancer, or
• Consumption of too much animal fat has been associated with colon
cancer—a reduction in fat consumption is a good idea for a number of
• Consuming about 20 to 30 grams of plant fiber daily—about twice the
U.S. average—can reduce the risk of colon cancer.
• Fruits and vegetables are good sources of soluble and insoluble fiber.
Lifestyle Factors (continued)
• Vitamins including C, E, and A may offer some protection against some
cancers (although some recent research suggests that this may be ques-
• The role of diet in increasing the risk of some cancers is a focus of much
DNA is over 99.9 percent
identical for any two people
of the same sex.
• In the 1940s, researchers demonstrated that the genes from individual
bacteria could be combined in the laboratory without resorting to normal
• Research over a span of 30 years—often using E. coli bacteria—led to
the development of recombinant DNA technology.
• The technology demonstrated that genes from different sources can be
combined into the DNA molecule in a host cell.
• A genetically-modified organism (GMO) is one that carries recombinant
• A transgenic organism is a GMO that carries DNA from different species.
• The two realms are not mutually exclusive (that is, they overlap)
This glow-in-the-dark tobacco plant contains genes
from a bioluminescent organism.
• Insulin is a protein molecule produced by the pancreas to regulate the
level of glucose in the blood.
• Diabetes (diabetes mellitus) results if insufficient insulin is produced.
• A number of unhealthful outcomes can result from untreated diabetes.
Bovine and Porcine Insulin
• Beginning in the 1920s, diabetes was treated using insulin from the
pancreases of cows and pigs (bovine and porcine insulin).
• Allergic reactions sometimes result since their protein structures are
not exactly the same as in human insulin.
• By the 1970s, the supply of bovine and porcine insulin could not keep
up with the demand.
Human insulin (to the left) and
porcine insulin—the difference
in the protein structure is just
one amino acid: alanine versus
• Recombinant DNA technology has enabled the mass production of syn-
• Since the amino acid sequence for human insulin was already known,
researchers could identify the DNA nucleotide sequence that codes for
• Individual segments of DNA were synthesized and linked to form human
• The artificially-produced human genes were inserted into E. coli bacteria
that could rapidly multiply and produce large quantities of insulin protein.
Synthetic Insulin (continued)
Today, more than four million people in the United States
rely on synthetic insulin.
• Agricultural crops—including wheat and corn—have been selectively bred
since antiquity to enhance their uses.
• DNA technology is now replacing traditional breeding programs to improve
• Some corn varieties, for example, have been genetically modified to resist
the European corn borer.
• DNA technology has revolutionized forensics, the scientific analysis of
evidence in crime scene and other legal investigations.
• The DNA sequence of every person is unique except in monozygotic
• DNA “fingerprinting” can determine if genetic material is from the same
person or different people.
• DNA fingerprinting has become a standard method for medical forensics,
law enforcement, and legal proceedings since its introduction in 1986.
• DNA can be obtained from many body sources including blood, tissues,
hair, bone, saliva, and semen.
• The technique is being used in an increasing number of legal and civil
More Recent Applications
• DNA technology continues to be used in identifying small fragments of
human remains from the terror attacks of September 11, 2001.
• DNA has also been used to exonerate prisoners who were innocent of
the charged crimes.
From the website of an appeals
attorney specializing in DNA evidence.
DNA Fingerprinting Process
• The analysis of DNA “fingerprints” consists of several major steps:
1. DNA collection, including maintaining the chain of custody.
2. Amplifying (copying) the DNA to provide a sufficient sample.
3. Cutting the DNA into fragments and arranging them into a pattern.
4. Comparing the DNA markers or fragments from different sources.
• The amplification process continues to be improved to allow the use
of increasingly-smaller samples of DNA.
Establishment of Paternity
• In cases involving the establishment of paternity, blood typing can rule-
out some possibilities—however, it cannot conclusively determine who is
the father of conception.
• Comparing DNA samples from the mother, child, and purported father
can definitively establish paternity.
• Recently, it was shown that Thomas Jefferson (the third U.S. President)
or a close relative fathered at least one of the children of his slave, Sally
Human Genome Project
• The human genome consists of about 3.2 billion nucleotide pairs and
• The human genome project, undertaken by an international consortium
of government-funded research groups, is completed and has published
much of its data.
• An understanding of the human genome has been a challenge due to its
large size, and because only relatively small segments of DNA actually
code for mRNA and tRNA.
• Much of human DNA consists of repetitive patterns of nucleotides (A, C,
• Segments of DNA containing thousands of base repetitions occur at the
centromeres and the ends of chromosomes, possibly for structural sup-
• Other repetitive patterns of up to several hundred nucleotides are found
between individual genes.
• The markers used in DNA fingerprinting are the repetitive patterns since
they are unique to the individual.
• Human gene therapy employs recombinant DNA to treat some types of
disorders and diseases.
• Gene therapy might be used to correct a genetic disorder—possibly
permanently, or in other instances just long enough to treat a medical
Gene Therapy Process
• The gene therapy process involves taking a normal gene from a donor,
and isolating and cloning it using recombinant DNA technology.
• The gene of the recombinant DNA is inserted into a vector—usually a
non-harmful DNA virus.
• The virus is injected into the patient so that the gene can insert itself into
• The newly-introduced gene is transcribed and translated to produce the
• Bone marrow stem cells, which produce cells for the blood and immune
system, are currently good candidates for this type of gene therapy.
http://www.em1.molmed.uni-erlangen.de Fetal Gene Therapy
The University of Southern California is
a pioneer in fetal gene therapy—the
research is conducted just a few miles
from the ELAC campus.
• Early concerns, including that recombinant DNA technology could create
deadly new microbes, are still being addressed by national governments.
• Laboratories must adhere to strict guidelines to ensure the microbes are
not accidentally released.
• They must adhere to strict procedures
to prevent worker contamination and
• The microbes are genetically-crippled
so that cannot reproduce and survive
outside the laboratory.
• Potentially dangerous experiments
have been restricted or banned.
Science fiction film from the early-1970s
Ethical and Moral Issues
• DNA technology raises legal, ethical, and moral questions, and often
with few clear answers.
• Should genetic engineering of gametes and zygotes be permitted for
desirable physical and mental characteristics in children?
• Should we allow genetic changes that could be beneficial today, but
possibly detrimental to the long-term health and survival of a species
including our own?
Ethical and Moral Issues (continued)
• Should we record the DNA fingerprint of every person, possibly as
early as birth?
• Should employers and insurance companies be allowed to screen
job applicants for potentially harmful genes?
• Should we take on a creator role for producing offspring including
• The list of questions is long—the issues need debate and careful
deliberation by society.