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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