22% Pre-2001 (HGP) Cases of genetic pre-determinism are rare. Gene regulation allows for adaptation...
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Transcript of 22% Pre-2001 (HGP) Cases of genetic pre-determinism are rare. Gene regulation allows for adaptation...
unknown25%
gene expression22%
metabolism17%
defense12%
communication12%
structure (motility)8%
Cell Division4%
Function of Human Genes
22%
Pre-2001 (HGP)Cases of genetic pre-determinism are rare.
Gene regulation allows for adaptation to environmental changes for an individual organism in the present.
Mutations allow for adapatation to environmental changes for a species over generations
Epigenetic changes allows for adaptation to current environmental changes for an individual organism to be passed on to its offspring.
Phage15 coat proteins
Infects E. coli50,000 bp ds DNA
E Coli cell
Phage binds to Cell membrane....
...... and inserts dsDNA into cell
In the lytic phase the cell replicates the phage DNA
New phage particles are created ….
Then the cell is lysed and the virus is released to the environment to seek new hosts.
Petri Dish with Nutrients
With bacterial growth Add phage – plaque forms
E Coli cell
Lysogenic Phase
DNA inserted into bacterial chromosome
Dormant phage’s DNA Copied with each bacterial cell division cycle.
Petri Dish plaquesE. Coli cells (lysogenic) reclaim plaque areas, but give ‘turbid’ appearance.
Lysogenic E Coli cells are immune to l phage infection.
DNA damage can be induced by UV light and causes switch from lysogenic to lytic phase.
yes
yes
Lytic
Is host DNA Damaged? (UV) no
no
Lysogenic
Dormancy
phage infects E coli Cell
very early phase (N/cro)
early phase (cII/cIII)
Is host well fed?
|=12=10|=10=cIII=N=OL=cI=OR=cro=cII=2=Q=3=| att
|=10=cIII=N=OL=cI=OR=cro=cII=2=Q=3=|=12=10| cos
attahed to host chromosome
in host unattached
in virus particle
2 = Replication genes3 = Lysis genes12 = Tail Protein genes10 = Head Protein genes
Lytic Phase
10: = 8 == Int == Xis == Lysogenic phase
PI
|=10=cIII=N= OL=cI=OR=cro=cII=2=Q=3=|=12=10| cos
PRM PR
PRE
PI
PL
REGULATORY GENES
cI: ( Repressor) & Activator (favors lysogenic phase)
cII: Activator (favors cI production over cro & Int)
cro: activator & repressor (favors lytic phase)
cIII: protects cII from proteases
N & Q: antiterminators – bypass transcription stop signal
|=10=cIII=N= OL=cI=OR=cro=cII=2=Q=3=|=12=10| cos
PRM PR
PRE
PI
PL
PI PL PRM PR PRE PR’
LYS = cIII = N = OL = cI = OR = cro = cII = Q=Lyt
cro+-cro-
PI PL PRM PR PRE PR’
LYS = cIII = N = OL = cI = OR = cro = cII = Q=Lyt
cI-cI+-
cII+
lysogenic
lytic
yes
Lytic
no
Lysogenic
Dormancy
phage infects E coli Cell
very early phase (N/cro)
early phase (cII/cIII)
Is host well fed?
↓[bacetrial protease] allows cIII time to protect cII. cI eventually dominates cro, and Int production. Int inserts phage DNA into host chromosome.
↑[bacetrial protease] destroys cII and cro dominance over cI is maintained.
PI PL PRM PR PRE PR’
LYS = cIII = N = OL = cI = OR = cro = cII = Q=Lyt
<<< PRM PR >>>
OR1OR
2OR3
DNAdouble helix B Form
majorgroove
minor groove
N
NN
N NN
NO
OH
CH
3 A
T
Major Groove
Minor Groove
H H
N
NN
N N
N
NO
OH
CH
3
T
H H
GlnCH2
NH H
O=C
CH2
R
RR
Hydrophobic Contact H-bonds to
Major Groove
-TurnHTH Motif
Lambda Phage Repressor Protein
cro
cro dimer
cI dimer
<<< PRM PR >>>
OR1OR
2OR3
1st on 2nd onOR
1 1 1OR
2 1 1OR
3 10 (10)
1st on 2nd onOR
1 10 ---OR
2 1 5OR
3 1 1
|=10=cIII=N=cI=OR=cro=cII=2=Q=3=|=12=10| cos
<<< PRM PR >>>
OR1OR
2OR3
cro
1st on 2nd onOR
1 1 1OR
2 1 1OR
3 10 (10)
RNA Pol
cro is expressed, cI is repressed.
|=10=cIII=N=cI=OR=cro=cII=2=Q=3=|=12=10| cos
<<< PRM PR >>>
OR1OR
2OR3
cro
High [cro] represses both PRM & PR
cro cro
PRM PR OR
1OR2OR
3
-repressor binding blocks PR
1st on 2nd onOR
1 10 ---OR
2 1 5OR
3 1 1
RNA Pol
… and activates PRM
|=10=cIII=N=cI=OR=cro=cII=2=Q=3=|=12=10| cos
<<< PRM PR >>>
OR1OR
2OR3
High [cI] represses PR & PRM
Yes – SOS reponse genes activated
Lytic
Is host DNA Damaged? (UV) no
Lysogenic
Dormancy
phage infects E coli Cell
very early phase (N/cro)
early phase (cII/cIII)
[cI] remains high. Phage remains dormant. cI inhibits growth of any late-coming phage.
E coli SOS ResponseE coli contains 17 SOS genes — e.g. HSPsencode DNA repair/recombination genes — LexA & RecA
LexA Repressor of SOS operon
LexA contains HTH motif & similar AG sequence to cI
HTH
RecA Function
Low [ ] under ‘normal’ circumstances
binds to ssDNA: complex cleaves LexA at AG
[RecA] - ssDNA + ATP dsDNA + ADP
If l phage lysogen then RecA cleaves cI and induces lytic phase shift
yes
Lytic
Is host DNA Damaged? (UV) no
Lysogenic
Dormancy
phage infects E coli Cell
very early phase (N/cro)
early phase (cII/cIII)
↑RecA-ssDNA destroys cI, and [cro] recovers dominance over cI. Xis expression removes phage DNA from host chromosome. Lytic phase commences.
[cI] remains high. Phage remains dormant. cI inhibits growth of any late-coming phage.