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Transcript
Ch. 18:
The Genetics of
Viruses and Bacteria
I. Intro
A. Bacteria and viruses are the simplest
biological systems. Most protein synthesis
research was done on bacteria.
B. Bacteria and viruses are also of interest
so that we can better understand the
diseases they cause.
C. Bacteria are prokaryotic organisms, and are
much smaller and simpler than eukaryotes.
D. Viruses are smaller and simpler still, lacking
the structure and most metabolic
machinery in cells.
-Viruses are made
up of nucleic acids
and a protein coat.
II. The Genetics of Viruses
A. Researchers discovered viruses by studying
a plant disease.
1. In 1883, Adolf Mayer studied tobacco
mosaic disease.
a. This disease causes stunted growth
and mottled plant leaves in tobacco
plant.
b. Mayer found that the disease was
infectious when he sprayed sap
from diseased leaves onto healthy
plants and caused healthy plants to
become diseased.
2. He said that a bacteria caused the
disease until Dimitri Ivanovsky
demonstrated that the sap was still
infectious even after passing through
a filter designed to remove bacteria.
3. In 1897, Martinus Beijerinck showed that
sap from one generation could infect a
second generation of plants – he showed
that the pathogen had heredity.
a. Beijerinck also determined that the
pathogen could reproduce only within
a host.
4. In 1935, Wendell Stanley crystallized the
pathogen, the tobacco mosaic virus
(TMV).
B. A virus is a genome enclosed in a protective
coat.
1. Since cells cannot be crystallized,
Stanley’s crystallization of viruses was an
indicator that viruses are not made up of
cells.
2. Viruses are infectious particles made up
of nucleic acids encased in a protein coat,
and sometimes a membranous envelope.
3. Viruses range in size from 20nm to barely
resolvable under a light microscope.
4. Viral nucleic acids can be:
-double-stranded DNA
-single-stranded DNA
-double-stranded RNA
-single-stranded RNA
 depending on the specific type of virus.
5. Some viruses only have a few genes,
while others have hundreds.
6. The capsid: the protein shell
a. Capsids are built from a large number
of protein subunits called capsomeres.
b. The tobacco mosaic virus has over
1,000 copies of the same protein
to make the capsid.
c. An adenovirus
has 252
identical
proteins
arranged
into a
polyhedral
capsid as an
icosahedron.
d. Some viruses have
viral envelopes that
are membranes
derived from a host
cell.
e. They can also have
viral proteins and
glycoproteins.
f. The most complex capsids are found
on the phages that infect bacteria.
-The T-even phages
that infect E. coli
have a 20-sided
capsid head that
encloses their DNA
and protein tail
piece that attaches
the phage to the
host and injects
the phage DNA inside.
C. Viruses can only reproduce within a host:
overview
1. Viruses are obligate intracellular
parasites; they can only reproduce within
a host cell.
a. They lack enzymes and ribosomes.
2. They can only infect a limited range of
hosts.
3. Some viruses identify host cells by a
“lock-and-key” fit between proteins on
the outside of virus and specific receptor
molecules on the host’s surface OR
some viruses have a wide range of hosts
(ex. Rabies virus).
4. Most viruses target specific tissues.
Example: Human cold viruses infect only
the cells lining the upper respiratory tract.
The AIDS virus binds only to certain
white blood cells.
5. Infection begins when the viral nucleic
acid is inserted into the host.
6. Once inside, the viral genome takes over
its host, reprogramming
the cell to copy viral nucleic acid and
manufacture proteins from the viral
genome.
7. The nucleic
acid molecules
and
capsomeres
then selfassemble into
viral particles
and exit the
cell.
D. Phages reproduce using lytic and lysogenic
cycles
1. The lytic cycle: the phage reproductive
cycle culminates in the death of the host.
a. Virulent phages reproduce only by a
lytic cycle.
b. Some bacteria have defense
mechanisms against viruses:
-Some bacterial mutants have
receptors sites that are no longer
recognized by a particular type of
phage.
-Some bacteria produce restriction
nucleases that recognize and cut up
foreign DNA.
2. Lysogenic cycle: the phage genome
replicates without destroying the host cell.
a. Temperate phages, like phage
lambda, use both lytic and lysogenic
cycles.
b. In the lysogenic cycle, the viral DNA
molecule, during the lysogenic cycle, is
incorporated by genetic recombination
into a specific site on the host cell’s
chromosome.
c. At this stage, the phage is called a
prophage, and one of its genes codes
for a protein that represses most other
prophage genes to “silent” the genome.
d. Each time the bacterial cell divides,
it will replicates its own DNA, including
the viral DNA. Each time the bacteria
divides, it will pass on the viral DNA
to the daughter cells.
e. Sometimes the viral genome exits the
bacterial chromosome and initiates a
lytic cycle.
This switch from lysogenic to lytic
may be initiated by an environmental
trigger.
The prophage in a lysogenic cycle will exit the
bacteria genome and cause a lytic cycle.
E. Animal viruses are
diverse in their
modes of infection
and replication.
1. Viruses differ in
the type of
nucleic acid
they have.
2. They also differ
on the presence
or absence of
a protein capsid.
3. Viruses with an outer envelope use the
envelope to enter a host cell.
a. Glycoproteins on the envelope bind
to specific receptors on the host’s
membrane.
b. The envelope fuses with the host’s
membrane, transporting the capsid
and viral genome inside.
c. The viral
genome
duplicates
and directs
the host’s
protein
synthesis
machinery to
synthesize
capsomeres
with free
ribosomes &
glycoproteins
with bound
ribosomes.
d. After the
capsid and
viral genome
self-assemble,
they bud from
the host cell
covered with
an envelope
derived from
the host’s
cell membrane,
including viral
glycoproteins.
These viruses do
not always kill the host.
4. Some viruses have envelopes that are
not derived from plasma membrane.
a. The herpesvirus is derived from the
nuclear envelope of the host.
b. The herpesvirus has double-stranded
DNA and they reproduce within the
cell nucleus using viral and cellular
enzymes to replicate and transcribe
their DNA.
c. Their DNA can be incorporated into
host DNA. When they do, they are
called a provirus.
d. The provirus remains latent within
the nucleus until triggered by stress
to leave the genome and initiate
active viral production.
F. Viruses that have RNA as genetic material:
1. Some viruses have single-stranded RNA
(class IV), the genome acts as mRNA
and is translated directly.
2. In other cases, (class V), the RNA
genome serves as a template for mRNA
and for a complementary RNA (to make
more of the RNA genome).
3. All viruses that require RNA -> RNA
synthesis to make mRNA use a viral
enzyme that is packaged with the
genome inside the capsid.
4. Retroviruses (class IV) have the most
complicated reproductive cycles:
a. These viruses carry an enzyme,
reverse transcriptase, which
transcribes DNA from an RNA
template.
b. The newly made DNA is then inserted
into the animal genome as a provirus.
Proviruses never leave the host
genome, unlike prophages.
c. The host’s RNA polymerase transcribes
the viral DNA into more RNA molecules.
The RNA strands can serve as
mRNA for viral proteins, or as
genomes for new virus particles
released from the cell.
d. HIV (Human immunodeficiency
virus (HIV), the virus that causes
AIDS (acquired immunodeficiency
syndrome) is a retrovirus.
-viral envelope
w/ glycoproteins
-a capsid
-two identical
RNA strands
-two reverse
transcriptase
enzymes
How does HIV infect a
white blood cell?
1. HIV fuses with host
cell membrane.
2. Reverse transcriptase
synthesizes a
complementary DNA
strand to the viral RNA.
3. Reverse transcriptase
synthesizes a second
DNA strand
complementary to the
first DNA strand.
4. The new double strand
DNA is incorporated as a
provirus into the host DNA.
5. Proviral genes are
transcribed into RNA.
6. The RNA serves as
mRNA for translation
of HIV proteins. It is
also used as genomes
for the next generation
of viruses.
7. Capsids are assembled
around viral genomes
and reverse
transcriptase molecules.
8. The viruses bud off the
host cell.
G. Causes and prevention of viral diseases in
animals:
1. Some viruses cause animal cell
lysosomes to release their hydrolytic
enzymes, thus destroying the cell.
2. Some viral proteins are toxic to cells.
3. Some viruses cause the cell to produce
toxins that can kill the cell.
4. Viral damage can be permanent (polio
causes nerve damage) or temporary
(the cold virus).
5. Many temporary symptoms, such as
fever, aches, and inflammation is due to
the body’s own efforts at defending itself
against infection.
6. Vaccines are harmless variants or
derivatives of pathogens that stimulate
the immune system to act against an
actual pathogen.
a. The first vaccine was developed in the
late 1700s by Edward Jenner to fight
smallpox.
b. He found that milkmaids who were
exposed to cowpox (milder and similar
to smallpox) were resistant to
smallpox.
c. In 1796, Jenner infected a farmboy
with cowpox. Later, the boy was
exposed to smallpox and seemed to
resist the disease.
d. Because cowpox is so similar to smallpox, an exposure to cowpox causes
the immune system to react vigorously
against smallpox.
e. Vaccines can prevent disease, but they
cannot treat or cure disease.
f. Antibiotics only work against bacteria.
They work by inhibiting bacterial
enzymes. Viruses have few or no
enzymes.
g. However, AZT inhibits HIV reproduction
by interfering with reverse transcriptase. Acyclovir inhibits herpesvirus
DNA synthesis.
H. Emerging viruses:
1. HIV (1980’s)
2. New strains of the influenza (flu) virus
3. Ebola (fever, severe bleeding)
The causes of these viruses:
-Mutations
-spread from one species to another
(3/4 of new human viruses come from
other animal species – Ex. Hantavirus
comes from deer mice)
-spread from a small population to the
rest of the world (HIV from Africa)
I. Some viruses cause cancer:
1. First to discover this was Peyton Rous
when in 1911, he discovered that a virus
causes cancer in chickens.
2. Tumor viruses: retrovirus, papovavirus,
adenovirus, and herpesvirus types.
3. Hepatitis B can cause liver cancer.
4. Epstein-Barr virus, which causes
infectious mononucleosis, has been linked
to several types of cancer in parts of
Africa, notably Burkitt’s lymphoma.
5. Papilloma viruses are associated with
cervical cancers.
6. The HTLV-1 retrovirus causes a type of
adult leukemia.
7. Viruses may carry oncogenes that
trigger cancerous characteristics in cells.
(Oncogenes = genes that causes cancer.)
-Viruses can also turn on
proto-oncogenes (genes that code for
growth factors that regulate the cell
cycle).
J. Viroids and Prions:
1. Viroids are small pieces of circular
RNA that infect plants. These viroids can
stunt plant growth.
2. Prions are infectious proteins that spread
a disease.
a. Prions cause several degenerative
brain diseases including scrapie in
sheep, “mad cow disease”, and
Creutzfeldt-Jacob disease in humans.
b. Scientists hypothesize that prions are
forms brain proteins that are
misfolded.
c. They can convert a normal protein
into the prion version, creating a chain
reaction that increases their numbers.
K. Virus evolution:
1. Because viruses need cells to survive, it
is thought that they evolved after cells.
2. It is hypothesized that viruses originated
from fragments of cellular nucleic acids
that could move from one cell to another.
3. Viruses probably came from plasmids
and transposons.
a. Plasmids are small, circular DNA
molecules found in bacteria and yeast
that are separate from chromosomes.
b. Transposons are DNA segments that
can move from one location to another
within a cell’s genome.
III.The Genetics of Bacteria
A. The short generation span of bacteria help
them to adapt to changing environments.
1. Bacteria are very adaptable.
2. Bacteria have a circular double strand of
DNA.
a. In E. coli, the chromosomal DNA
consists of about 4.6 million nucleotide
pairs with about 4,300 genes.
b. Tight coiling of the DNA results in a
dense region called the nucleoid.
3. In addition to the chromosome, bacteria
have plasmids, which are smaller circles
of DNA.
a. Plasmids have a few genes on them.
4. Bacteria divide
by binary fission.
The chromosome
replicates from a
single origin of
replication.
5. Bacteria replicate very rapidly:
-under optimal conditions, a population
of E. coli can double in 20 minutes, and
producing a colony of 107 to 108 bacteria
in as little as 12 hours.
-In the human colon, E. coli reproduces
rapidly enough to replace the 2 x 1010
bacteria lost each day in feces.
a. Most of the bacteria in a colony are
genetically identical to the parent cell.
b. However, the spontaneous mutation
rate of E. coli is 1 x 10-7 mutations per
gene per cell division.
There are ~2,000 bacteria in the
human colon that have a mutation
in that gene per day.
B. Genetic recombination produces new strains
of bacteria.
1. In addition to mutations, genetic
recombination can add to the diversity of
bacteria.
2. Recombination in bacteria is defined as
the combining of DNA from two
individuals into a single genome.
3. This recombination has 3 processes:
-transformation
-transduction
-conjugation
a. Transformation: is the alteration of a
bacterial cell’s genotype by the uptake
of naked, foreign DNA from the
surrounding environment.
-For example, harmless Streptococcus
pneumoniae bacteria can be
transformed to pneumonia-causing
cells.
-Many bacterial species have surface
proteins that are specialized for the
uptake of naked DNA.
They will only uptake DNA from a
closely related bacteria.
b. Transduction: occurs when a phage
carries bacterial genes from one host
cell to another.
1. General transduction: a small piece
of the host cell’s degraded DNA is
packaged within a capsid, rather than
the phage genome.
2. Specialized transduction: occurs via
a temperate phage.
When the prophage viral genome
exits the host chromosome, it sometimes takes with it a small region of
adjacent bacterial DNA.
This bacterial DNA will be injected
along with the viral DNA when the
virus infects another bacteria.
-Both transduction types use a phage as a vector
to transfer genes between bacteria.
c. Conjugation: transfers genetic
material between two bacterial cells
that are temporarily joined.
1.One cell (“male”) donates DNA and
its “mate” (“female”) receives the
genes.
2.A sex pilus from
the male initially
joins the two cells
and creates a
cytoplasmic
bridge between
cells.
3.The “maleness” is the ability to form
a sex pilus and donate DNA is the
result from an F factor, a section
of the bacterial chromosome or as a
plasmid.
4.Plasmids, including the F plasmid, are
small, circular, self-replicating DNA
molecules.
5.Episomes, like the F plasmid, can
undergo reversible incorporation into
the cell’s chromosome.
6.Plasmids generally benefit the
bacteria. They usually have only a
few genes.
7.The F plasmid consists of about 25
genes, most required for the
production of sex pilli.
8.Cells with an F plasmid are called F+
and they pass this condition to their
offspring.
9.Cells lacking the F plasmid are called
F-, and they function as DNA
recipients.
When an F+ and F- cells meet, the
F+ cell will give the F- cell a copy of
the F plasmid.
10.The F plasmid can integrate into the
bacterial chromosome. The resulting
cell is called an Hfr cell and it acts
as a male during conjugation.
-The Hfr bacterial DNA will replicate (at
arrowhead) and will be transferred to the
F- cell. Most of the time, the conjugation
bridge is destroyed before the entire
chromosome and F plasmid can be
transferred.
Recombination between homologous fragments take place and the DNA not part of
the resulting chromosome is degraded.
C. R Plasmid: The drug resistance plasmid.
1. Genes on the R plasmid codes for
enzymes that specifically destroy certain
antibiotics, like tetracycline or ampicillin.
2. R plasmids also contain genes that code
for sex pili, allowing for R plasmids to be
transferred from bacteria to bacteria.
When a bacterial population is exposed
to an antibiotic, individuals with the
R plasmid will survive and increase in
the overall population.
D. Transposons: piece of DNA that can move
from one location to another in a cell’s
genome.
1. Transposons can bring multiple copies for
antibiotic resistance into a single R
plasmid by moving genes to that location
from different plasmids.
Explanation for multiple resistance
genes on a single R plasmid.
2. Two types of transposon movement:
a. “Cut-and-paste transposition” – when a
transposon “jumps” from one location
to another location on the genome.
b. “Replicative transposons:” transposon
replicates and its copy inserts elsewhere
in the genome.
3. Insertion sequences: The simplest
bacterial transposon, an insertion
sequence, consists only of the DNA
necessary for the act of transposition.
a. The only gene in the sequence codes for
an enzyme called transposase, which
catalyzes movement of the transposon.
b. Tranposase recognizes the inverted
repeats as the edges of the transposon.
c. Transposase cuts the transposon from its
initial site and inserts it into the target
site.
d. Gaps in the DNA
strands are filled in
by DNA polymerase,
creating direct
repeats, and then
DNA ligase seals
the old and new
material.
Insertion sequences
cause mutations
when they happen
to land within the
coding sequence of
a gene or within a
DNA region that
regulates gene expression.
4. Composite transposons (complex
transposons): include extra genes sandwiched between two insertion sequences.
Composite transposons may help
bacteria adapt to new environments.
5. Transposons were first
discovered in the 1940’s by
Barbara McClintock who
studied color changes in
maize (corn) kernels.
She hypothesized that the
changes in kernel color only
made sense if mobile genetic
element moved from other
locations in the genome to the
genes for kernel color.
When transposons moved next to genes for
kernal color, they either activated or
inactivated those genes.
E. The control of gene expression enables
individual bacteria to adjust their
metabolism to environmental change.
1. Cells can regulate which genes are
expressed. Cells can adjust the activity
of enzymes by feedback inhibition.
2. In 1961, Francois Jacob and Jacques
Monod proposed the operon model for
the control of gene expression in bacteria.
The operon model consists of 3 parts:
a.The genes the operon controls.
b.A promoter region where RNA polymerase binds to.
c.An operator region between the
promotor and the first gene which acts
as an “on-off switch”.
3. The Operon Model:
a. If there is no repressor, the operon is
turned on and the genes will be
expressed.
b. However, if a repressor protein, a
product of a regulatory gene, binds
to the operator, it can prevent
transcription of the operon’s genes.
c. Regulatory genes are continuously
expressed at low rates.
d. Many repressors contain allosteric sites
where molecules bind to activate it.
Ex.: Tryptophan acts as a corepressor,
activating the repressor so that the
operon is turned off. At low levels of
tryptophan, most of the repressors are
inactivated, and the operon is on.
When the operon is on, the genes are
turned on. The tryp operon contains
genes that code for enzymes that make
the amino acid tryptophan.
Important!: How is this an example
of feedback inhibition?
e. The tryp operon is an example of a
repressible operon. In contrast, there
are inducible operons; operons that are
turned on when molecules react with
the regulatory protein.
-In inducible operons, an inducer molecule binds to the repressor and
inactivates it, turning on the operon.
f. An example of an inducible operon:
the lac operon.
-Contains genes for enzymes that
help metabolize lactose sugar.
-In the absence of lactose, the operon
is turned off as the repessor binds to
the operator.
-When lactose is present, allolactase, an
isomer of lactose, binds to the repressor,
inactivating it.
-Inducible enzymes usually function in
catabolic pathways, digesting nutrients to
simpler molecules (lac operon).
-Repressible enzymes generally function in
anabolic pathways, synthesizing end
products (tryp operon).