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-



cI-cI+-

cII+

lysogenic

lytic

yes

Lytic

no

Lysogenic

Dormancy




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.



<<< 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.


<<< 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


<<< PRM PR >>>

OR1OR

2OR3

High [cI] represses PR & PRM

Yes – SOS reponse genes activated

Lytic


Lysogenic

Dormancy




[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


Lysogenic

Dormancy




↑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.

22% pre-2001 (hgp) cases of genetic pre-determinism are rare. gene regulation allows for adaptation...

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