Transcript Chapter 18.
Chapter 18
Viral and Bacterial Genetics
AP Biology
Hepatitis
Viral diseases
Polio
Measles
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Chicken
pox
2005-2006
Influenza: 1918 epidemic
30-40 million deaths world-wide
RNA virus
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2005-2006
Smallpox
Eradicated in 1976
vaccinations ceased in 1980
at risk population?
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2005-2006
Emerging viruses
Viruses that “jump” host
switch species
Ebola, SARS, bird flu,
hantavirus
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Ebola
SARS
hantavirus
A sense of size
Comparing size
eukaryotic cell
bacterium
virus
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2005-2006
What is a virus? Is it alive?
DNA or RNA enclosed in a protein coat
Viruses are not cells
Extremely tiny
electron microscope size
smaller than ribosomes
~20–50 nm
1st discovered in plants (1800s)
tobacco mosaic virus
couldn’t filter out
couldn’t reproduce on media
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like bacteria
2005-2006
Variation in viruses
Parasites
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plant virus
pink eye
lack enzymes for
metabolism
lack ribosomes for
protein synthesis
need host
“machinery”
2005-2006
Variation in viruses
A package of
influenza
bacteriophage
genes in transit
from one host
cell to another
“A piece of bad news
wrapped in protein”
– Peter Medawar
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2005-2006
Viral genomes
Viral nucleic acids
DNA
double-stranded
single-stranded
RNA
double-stranded
single-stranded
Linear or circular
smallest viruses
have only 4 genes,
while largest have
several hundred
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2005-2006
Viral protein coat
Capsid
crystal-like protein
shell
1-2 types of proteins
many copies of same
protein
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2005-2006
Viral envelope
Lipid bilayer membranes
cloaking viral capsid
envelopes are derived from
host cell membrane
glycoproteins on surface
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HIV
2005-2006
Generalized viral lifecycle
Entry
virus DNA/RNA enters host cell
Assimilation
viral DNA/RNA takes over host
reprograms host cell to copy
viral nucleic acid & build viral
proteins
Self assembly
nucleic acid molecules &
capsomeres then selfassemble into viral particles
exit cell
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2005-2006
Symptoms of viral infection
Link between infection & symptoms varies
kills cells by lysis
cause infected cell to produce toxins
fever, aches, bleeding…
viral components may be toxic
envelope proteins
Damage?
depends…
lung epithelium after the flu is repaired
nerve cell damage from polio is permanent
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Viral hosts
Host range
most types of virus can infect & parasitize
only a limited range of host cells
identify host cells via “lock & key” fit
between proteins on viral coat &
receptors on host cell surface
broad host range
rabies = can infect all mammals
narrow host range
human cold virus = only cells lining upper
respiratory tract of humans
HIV = binds only to specific white blood cells
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Bacteriophages
Viruses that infect bacteria
ex. phages that infect E. coli
lambda phage
20-sided capsid head
encloses DNA
protein tail attaches phage to
host & injects phage DNA
inside
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2005-2006
Bacteriophage lifecycles
Lytic
reproduce virus in
bacteria
release virus by
rupturing bacterial
host
Lysogenic
integrate viral DNA
into bacterial DNA
reproduce with
bacteria
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Lytic lifecycle of phages
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2005-2006
Lysogenic lifecycle of phages
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2005-2006
Defense against viruses
Bacteria have defenses against phages
bacterial mutants with receptors that are no
longer recognized by a phage
natural selection favors these mutants
bacteria produce restriction enzymes
recognize & cut up foreign DNA
It’s an escalating war!
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natural selection favors phage mutants
resistant to bacterial defenses
When do
we need to
cut DNA?
This will be
important!
RNA viruses
Retroviruses
have to copy viral RNA into host DNA
enzyme = reverse transcriptase
RNA DNA mRNA
host’s RNA polymerase now transcribes
viral DNA into viral mRNA
mRNA codes for viral components
host’s ribosomes produce new viral proteins
transcription
DNA
replication
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RNA
translation
protein
Why is this
significant?
Retroviruses
HIV
Human ImmunoDeficiency Virus
causes AIDS
Acquired ImmunoDeficiency
Syndrome
opportunistic diseases
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envelope with glycoproteins
for binding to specific WBC
capsid containing 2 RNA
strands & 2 copies of
reverse transcriptase
2005-2006
HIV infection
HIV enters host cell
macrophage & CD4 WBCs
cell-surface receptor
reverse transcriptase
synthesizes double stranded
DNA from viral RNA
high mutation rate
Transcription produces more
copies of viral RNA
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translated into viral proteins
proteins & vRNA self-assemble
into virus particles
released from cell by “budding”
or by lysis
2005-2006
HIV treatments
inhibit vRNA replication
AZT
thymine mimic
protease inhibitors
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stops cleavage of polyprotein into
capsid & enzyme proteins
2005-2006
Potential HIV treatments
Block receptors
chemokines
bind to & block cell-surface receptors
11% of Caucasians have mutant receptor allele
Block vRNA replication
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CAF replication factor
2005-2006
Cancer viruses
Viruses appear to cause certain human
cancers
hepatitis B virus
linked to liver cancer
Epstein-Barr virus = infectious mono
linked to lymphoma
papilloma viruses
linked with cervical cancers
HTLV-1 retrovirus
linked to adult leukemia
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Cancer viruses
Transform cells into cancer cells after
integration of viral DNA into host DNA
carry oncogenes that trigger cancerous
characteristics in cells
version of human gene that normally
controls cell cycle or cell growth
Most tumor viruses probably cause
cancer only in combination with other
mutagenic events
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Prions
Misfolded proteins
infectious
make plaques
(clumps) &
holes in brain
as neurons die
Creutzfeldt-Jakob disease
“mad
cow” disease
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2005-2006
1982 | 1997
Protein as information molecule?!
Prions challenge Central Dogma
transmit information to other proteins
Pn
Pd
Stanley Prusiner
UC School of Medicine
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proteinaceous infectious 2005-2006
molecule
Ch. 18: Control of
Prokaryotic (Bacterial) Genes
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2007-2008
Prokaryotic Gene Control
Bacteria need to respond quickly to
changes in their environment
Transcription and translation happen
simultaneously…they are “coupled!”
Transcription is what is regulated.
Lack of nucleus makes this very efficient!
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Bacterial metabolism
Bacteria need to respond quickly to
changes in their environment
if they have enough of a product,
need to stop production
why? waste of energy to produce more
STOP
GO
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how? stop production of enzymes for synthesis
if they find new food/energy source,
need to utilize it quickly
why? metabolism, growth, reproduction
how? start production of enzymes for digestion
Remember Regulating Metabolism?
Feedback inhibition
- = inhibition
product acts
as an allosteric inhibitor
of
1st enzyme in
tryptophan pathway
but this is wasteful
production of enzymes
Oh, I
remember this
from our
Metabolism Unit!
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-
Different way to Regulate Metabolism
Gene regulation
- = inhibition
instead of blocking
enzyme function,
block transcription of
genes for all enzymes
in tryptophan
pathway
saves energy by
not wasting it on
unnecessary
protein synthesis
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Now, that’s a
good idea from a
lowly bacterium!
-
-
Gene regulation in bacteria
Cells vary amount of specific enzymes
by regulating gene transcription
turn genes on or turn genes off
turn genes OFF example
if bacterium has enough tryptophan then it
STOP doesn’t need to make enzymes used to build
tryptophan
turn genes ON example
if bacterium encounters new sugar (energy
GO source), like lactose, then it needs to start
making enzymes used to digest lactose
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Bacteria group genes together
Operon
genes grouped together with related functions
example: all enzymes in a metabolic pathway
Two types: INDUCIBLE and REPRESSIBLE
promoter = RNA polymerase binding site
single promoter controls transcription of all genes in operon
transcribed as one unit & a single mRNA is made
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operator = DNA binding site of repressor protein
Operon model
Operon:
operator, promoter & genes they control
serve as a model for gene regulation
RNA
polymerase
RNA repressor
polymerase
gene1
gene2
gene3
gene4
1
2
3
4
enzyme1
enzyme2
enzyme3
enzyme4
mRNA
promoter
DNA
operator
Repressor protein turns off gene by
blocking
AP BiologyRNA polymerase binding site.
repressor
= repressor protein
Repressible operon: tryptophan
Synthesis pathway model
When excess tryptophan is present,
it binds to tryp repressor protein &
triggers repressor to bind to DNA
RNA
polymerase
RNA
trp repressor
polymerase
gene1
gene2
gene3
gene4
1
2
3
4
enzyme1
enzyme2
enzyme3
enzyme4
mRNA
promoter
blocks (represses) transcription
DNA
trp
operator
trp
trp
repressor
repressor protein
trp
trp
trp
trp
trp
trp
conformational change in
AP Biologyprotein!
repressor
trp
repressor
tryptophan
trp
tryptophan – repressor protein
complex
Tryptophan operon
What happens when tryptophan is present?
Don’t need to make tryptophan-building
enzymes
Tryptophan
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is allosteric regulator of repressor protein
Inducible operon: lactose
lac
lac
RNA
polymerase
lac
Digestive pathway model
lac
When lactose is present, binds to
lac repressor protein & triggers
repressor to release DNA
lac
lac
lac
RNA
lac repressor
TATA
polymerase
induces transcription
gene1
gene2
gene3
gene4
1
2
3
4
enzyme1
enzyme2
enzyme3
enzyme4
mRNA
promoter
operator
repressor
lac
conformational change in
AP Biologyprotein!
repressor
lac
repressor
DNA
repressor protein
lactose
lactose – repressor protein
complex
Lactose operon
What happens when lactose is present?
Need to make lactose-digesting enzymes
Lactose is allosteric regulator of repressor protein
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So how can these genes be turned off?
Repressor protein
binds to DNA at operator site
blocking RNA polymerase
blocks transcription
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UpRegulation – increase the rate!
Ex: CAP/cAMP system
When lactose is present
and glucose is low:
cAMP is high
cAMP activates
Catabolite Activator
Protein (CAP)
Increases the rate of
transcription by
100x!
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1961 | 1965
Jacob & Monod: lac Operon
Francois Jacob & Jacques Monod
first to describe operon system
coined the phrase “operon”
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Jacques Monod
Francois Jacob
Operon summary
Repressible operon
usually functions in anabolic pathways
synthesizing end products
when end product is present in excess,
cell allocates resources to other uses
Inducible operon
usually functions in catabolic pathways,
digesting nutrients to simpler molecules
produce enzymes only when nutrient is
available
cell avoids making proteins that have nothing to do,
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cell allocates resources to other uses
Don’t be repressed!
How can I induce you
to ask Questions?
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