Download Gene Expression

Gene Expression
Ch 11
Gene expression
• Genes to proteins
– Genotype to phenotype
• Produce specific proteins when and where
they are needed
lac Operon
• E. Coli make enzymes to utilize lactose
sugars
– Dependent on presence/absence of lactose
• 3 enzymes to take up and metabolize
lactose
– Genes that code for enzymes located next to
each other in DNA
Fig. 11-1b
OPERON
Regulatory Promoter Operator
gene
Lactose-utilization genes
DNA
mRNA
Protein
RNA polymerase
cannot attach to
promoter
Active
repressor
Operon turned off (lactose absent)
DNA
mRNA
RNA polymerase
bound to promoter
Protein
Lactose
Inactive
repressor
Operon turned on (lactose inactivates repressor)
Enzymes for lactose utilization
lac Operon
• Control sequence
– Promoter
– Operator
• Operon
– Genes, promoter and Operator
***Exist almost solely in prokaryotes
lac Operon
• Repressors
– Block RNA polymerase from binding
– Regulatory genes code for repressors
• Located outside the operon
Fig. 11-1b
OPERON
Regulatory Promoter Operator
gene
Lactose-utilization genes
DNA
mRNA
Protein
RNA polymerase
cannot attach to
promoter
Active
repressor
Operon turned off (lactose absent)
DNA
mRNA
RNA polymerase
bound to promoter
Protein
Lactose
Inactive
repressor
Operon turned on (lactose inactivates repressor)
Enzymes for lactose utilization
Repressors
• trp operon
– repressor is inactive alone
• When tryptophan present, binds to
repressor, enabling it to switch
transcription off
Fig. 11-1c
Promoter Operator
Gene
DNA
Active
repressor
Active
repressor
Tryptophan
Inactive
repressor
Inactive
repressor
Lactose
lac operon
trp operon
Activators
• Activators
– Turn operons on by binding to DNA
– Make it easier for RNA polymerase to bind
Differentiation
• Specialized in structure and function
– Results from selective gene expression
– Variety of cell types, expressing different
combination of genes
Fiure 11.2
Muscle cell
Pancreas cells
Blood cells
Differentiation
• Differentiated cells may retain all of their
genetic potential
• Most differentiated cells retain a complete
set of genes
Root of
carrot plant
Single cell
Figure 11.3
Root cells cultured
in nutrient medium
Cell division
in culture
Plantlet
Adult Plant
The Chromosome
• Packaging helps regulate
expression
• Histone proteins
– Aid in packaging and
ordering DNA
DNA double
helix (2-nm
diameter)
Histones
TEM
“Beads on
a string”
Linker
Nucleosome
(10-nm diameter)
Tight helical fiber
(30-nm diameter)
Supercoil
(300-nm diameter)
TEM
700
nm
Metaphase chromosome
The Chromosome
DNA double
helix (2-nm
diameter)
Histones
“Beads on
a string”
TEM
Linker
Nucleosome
(10-nm diameter)
Tight helical fiber
(30-nm diameter)
Supercoil
(300-nm diameter)
700
nm
TEM
• Nucleosome
– DNA-histone complex
involving DNA wound
around 8 histone protein
core
• Resembles beads on a
string
• Linkers
– Join consecutive
nucleosomes
• Packing presumably prevents
access of transcription
proteins
Metaphase chromosome
X chromosome
• In females, 1 x inactive in each cell
– Barr body
Two cell populations
in adult
Early embryo
Cell division
and random
X chromosome
inactivation
X chromosomes
Active X
Orange
fur
Inactive X
Inactive X
Figure 11.5
Allele for
orange fur
Allele for
black fur
Active X
Black fur
Proteins controlling transcription
• Regulatory proteins turn
off/on gene transcription
• Transcription factors
• Enhancers
• Silencers
• RNA splicing
Enhancers
Promoter
Gene
DNA
Activator
proteins
Transcription
factors
Other
proteins
RNA polymerase
Bending
of DNA
Figure 11.6
Transcription
Proteins controlling transcription
• Enhancers
Enhancers
– Activators bind and bend
DNA
– Interact with other
transcription factor
proteins
– Bind as complex to
promoter
• Silencers
• RNA splicing
Promoter
Gene
DNA
Activator
proteins
Transcription
factors
Other
proteins
RNA polymerase
Bending
of DNA
Figure 11.6
Transcription
Proteins controlling transcription
• Silencers
Enhancers
– Bind to DNA and inhibit
start of transcription
Promoter
Gene
DNA
Activator
proteins
Transcription
factors
Other
proteins
RNA polymerase
Bending
of DNA
Figure 11.6
Transcription
Splicing
• Alternate RNA splicing
– Splicing can occur in more than 1 way
– Different mRNA from same RNA transcript
Exons
DNA
RNA
transcript
or
RNA splicing
Figure 11.7
mRNA
Small RNA’s
• miRNA
• RNA interference
1
Protein
miRNA
miRNAprotein
complex
2
Target mRNA
4
3
mRNA degraded
OR
Translation blocked
Regulation of translation
•
•
•
•
Breakdown of mRNA
Initiation of translation
Protein activation
Protein breakdown
Folding of
polypeptide and
formation of
S—S linkages
Initial polypeptide
(inactive)
Cleavage
Folded polypeptide
(inactive)
Cascades
Egg cell
Egg cell
within ovarian
follicle
• Protein products
from one set of
genes activate
another set
• Homeotic gene
Protein
signal
Follicle cells
1
Gene expression
“Head”
mRNA
2
Embryo
Cascades of
gene expression
Body
segments
3
Gene expression
Adult fly
4
Signal transduction pathways
Signaling cell
• Series of molecular
changes that
converts signal on
cell surface to
specific response
inside cell
Signal
molecule
Receptor
protein
1
Plasma
membrane
2
3
Target cell
Relay
proteins
Transcription factor
(activated)
4
Nucleus
DNA
5
mRNA
Transcription
6
New
protein
Translation
Figure 11.14
Cloning
• A clone is an individual created by asexual
reproduction and thus is genetically
identical to a single parent
Cloning
• Regeneration
• Nuclear Transplantation
– Reproductive and Therapeutic cloning
Donor
cell
Nucleus from
donor cell
Implant blastocyst in
surrogate mother
Remove nucleus Add somatic cell
from adult donor
from egg cell
Clone of donor is born
(reproductive cloning)
Grow in culture to produce an
early embryo (blastocyst)
Remove embryonic stem Induce stem cells to
cells from blastocyst and form specialized cells
grow in culture
(therapeutic cloning)
Figure 11.10
Reproductive Cloning
• Not exact copy
– Behavioral differences
• Ethical questions
Therapeutic Cloning
• Medical potential
• Embryonic stem cells
• Adult stem cells
– Replace nonreproducing
specialized cells as
needed
– Only give rise to
Figure 11.12
certain tissues
Blood cells
Adult stem
cells in bone
marrow
Nerve cells
Cultured
embryonic
stem cells
Heart muscle cells
Different culture
conditions
Different types of
differentiated cells
Cancer
•
Divide uncontrollably
– Mutations whose protein products affect the
cell cycle
•
Oncogene
– Can cause cancer when present in a single
copy
Cancer
• Proto-oncogene
– Gene that has
potential to
become
oncogene
– Mutation or
virus
Proto-oncogene DNA
Mutation within
the gene
New promoter
Oncogene
Hyperactive
growthstimulating
protein in
normal
amount
Gene moved to
new DNA locus,
under new controls
Multiple copies
of the gene
Normal growthstimulating
protein
in excess
Figure 11.16A
Normal growthstimulating
protein
in excess
Cancer
• Tumor-suppressor
genes
Tumor-suppressor gene
Mutated tumor-suppressor gene
– Help prevent
uncontrolled growth
Figure 11.16B
Normal
growthinhibiting
protein
Defective,
nonfunctioning
protein
Cell division
under control
Cell division not
under control
Oncogene proteins and faulty tumor-suppressor
proteins can interfere with normal signal
transduction pathways
Growth-inhibiting
factor
Growth
factor
Receptor
Receptor
Target cell
Hyperactive
relay protein
(product of
ras oncogene)
issues signals
on its own
Normal product
of ras gene
Relay
proteins
Relay
proteins
Nonfunctional transcription
factor (product of faulty p53
tumor-suppressor gene)
cannot trigger
transcription
Transcription factor
(activated)
Transcription factor
(activated)
Normal product
of p53 gene
DNA
Nucleus
Protein that
stimulates
cell division
Figure 11.17A
Transcription
Transcription
Translation
Figure 11.17B
Protein that
inhibits
cell division
Translation
Protein absent
(cell division
not inhibited)
Cancer
• Series of genetic changes
– Colon cancer
Colon wall
1
2
Cellular
changes:
Increased
cell division
Growth of polyp
Growth of malignant
tumor (carcinoma)
DNA
changes:
Oncogene
activated
Tumor-suppressor
gene inactivated
Second tumorsuppressor gene
inactivated
3
Cancer
• Series of mutations
Chromosomes
1
mutation
2
mutations
Normal
cell
3
mutations
4
mutations
Malignant
cell
Figure 11.18B
Table 11.20