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Gene Expression Ch 11

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Page 1: Gene Expression Ch 11. Gene expression Genes to proteins –Genotype to phenotype Produce specific proteins when and where they are needed

Gene Expression

Ch 11

Page 2: Gene Expression Ch 11. Gene expression Genes to proteins –Genotype to phenotype Produce specific proteins when and where they are needed

Gene expression

• Genes to proteins– Genotype to phenotype

• Produce specific proteins when and where they are needed

Page 3: 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

Page 4: Gene Expression Ch 11. Gene expression Genes to proteins –Genotype to phenotype Produce specific proteins when and where they are needed

Fig. 11-1b

DNA

DNA

RNA polymerasecannot attach to promoter

Lactose-utilization genesPromoter OperatorRegulatorygene

OPERON

Protein

mRNA

Inactiverepressor

Lactose Enzymes for lactose utilization

RNA polymerasebound to promoter

Operon turned on (lactose inactivates repressor)

mRNA

Activerepressor

Operon turned off (lactose absent)

Protein

Page 5: Gene Expression Ch 11. Gene expression Genes to proteins –Genotype to phenotype Produce specific proteins when and where they are needed

lac Operon

• Control sequence– Promoter– Operator

• Operon– Genes, promoter and Operator

***Exist almost solely in prokaryotes

Page 6: Gene Expression Ch 11. Gene expression Genes to proteins –Genotype to phenotype Produce specific proteins when and where they are needed

lac Operon

• Repressors– Block RNA polymerase from binding– Regulatory genes code for repressors

• Located outside the operon

Page 7: Gene Expression Ch 11. Gene expression Genes to proteins –Genotype to phenotype Produce specific proteins when and where they are needed

Fig. 11-1b

DNA

DNA

RNA polymerasecannot attach to promoter

Lactose-utilization genesPromoter OperatorRegulatorygene

OPERON

Protein

mRNA

Inactiverepressor

Lactose Enzymes for lactose utilization

RNA polymerasebound to promoter

Operon turned on (lactose inactivates repressor)

mRNA

Activerepressor

Operon turned off (lactose absent)

Protein

Page 8: Gene Expression Ch 11. Gene expression Genes to proteins –Genotype to phenotype Produce specific proteins when and where they are needed

Repressors

• trp operon– repressor is inactive alone

• When tryptophan present, binds to repressor, enabling it to switch transcription off

Page 9: Gene Expression Ch 11. Gene expression Genes to proteins –Genotype to phenotype Produce specific proteins when and where they are needed

Fig. 11-1c

DNA

Inactiverepressor

Activerepressor

Inactiverepressor

Activerepressor

Lactose

Promoter

Tryptophan

Operator Gene

lac operon trp operon

Page 10: Gene Expression Ch 11. Gene expression Genes to proteins –Genotype to phenotype Produce specific proteins when and where they are needed

Activators

• Activators– Turn operons on by binding to DNA– Make it easier for RNA polymerase to bind

Page 11: Gene Expression Ch 11. Gene expression Genes to proteins –Genotype to phenotype Produce specific proteins when and where they are needed

Differentiation• Specialized in structure and function

– Results from selective gene expression– Variety of cell types, expressing different

combination of genes

Muscle cell Pancreas cells Blood cellsFiure 11.2

Page 12: Gene Expression Ch 11. Gene expression Genes to proteins –Genotype to phenotype Produce specific proteins when and where they are needed

Root ofcarrot plant

Root cells culturedin nutrient medium

Cell divisionin culture Plantlet Adult Plant

Single cell

Figure 11.3

Differentiation• Differentiated cells may retain all of their

genetic potential

• Most differentiated cells retain a complete set of genes

Page 13: Gene Expression Ch 11. Gene expression Genes to proteins –Genotype to phenotype Produce specific proteins when and where they are needed

The Chromosome• Packaging helps regulate

expression

• Histone proteins

– Aid in packaging and ordering DNA

DNA doublehelix (2-nmdiameter)

Histones

Linker“Beads ona string”

Nucleosome(10-nm diameter)

Tight helical fiber(30-nm diameter)

Supercoil(300-nm diameter)

Metaphase chromosome

700nm

TE

M

TE

M

Page 14: Gene Expression Ch 11. Gene expression Genes to proteins –Genotype to phenotype Produce specific proteins when and where they are needed

The Chromosome• 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

DNA doublehelix (2-nmdiameter)

Histones

Linker“Beads ona string”

Nucleosome(10-nm diameter)

Tight helical fiber(30-nm diameter)

Supercoil(300-nm diameter)

Metaphase chromosome

700nm

TE

M

TE

M

Page 15: Gene Expression Ch 11. Gene expression Genes to proteins –Genotype to phenotype Produce specific proteins when and where they are needed

X chromosome

• In females, 1 x inactive in each cell– Barr body

Early embryo

X chromosomes

Allele fororange fur

Allele forblack fur

Cell divisionand random

X chromosomeinactivation

Two cell populationsin adult

Active X

Inactive X

Inactive X

Active X

Orangefur

Black fur

Figure 11.5

Page 16: Gene Expression Ch 11. Gene expression Genes to proteins –Genotype to phenotype Produce specific proteins when and where they are needed

Proteins controlling transcription

• Regulatory proteins turn off/on gene transcription

• Transcription factors

• Enhancers

• Silencers

• RNA splicing

Enhancers Promoter

Gene

DNA

Activatorproteins

Otherproteins

Transcriptionfactors

RNA polymerase

Bendingof DNA

TranscriptionFigure 11.6

Page 17: Gene Expression Ch 11. Gene expression Genes to proteins –Genotype to phenotype Produce specific proteins when and where they are needed

Proteins controlling transcription• Enhancers

– Activators bind and bend DNA

– Interact with other transcription factor proteins

– Bind as complex to promoter

• Silencers• RNA splicing

Enhancers Promoter

Gene

DNA

Activatorproteins

Otherproteins

Transcriptionfactors

RNA polymerase

Bendingof DNA

TranscriptionFigure 11.6

Page 18: Gene Expression Ch 11. Gene expression Genes to proteins –Genotype to phenotype Produce specific proteins when and where they are needed

Proteins controlling transcription

• Silencers– Bind to DNA and inhibit

start of transcription

Enhancers Promoter

Gene

DNA

Activatorproteins

Otherproteins

Transcriptionfactors

RNA polymerase

Bendingof DNA

TranscriptionFigure 11.6

Page 19: Gene Expression Ch 11. Gene expression Genes to proteins –Genotype to phenotype Produce specific proteins when and where they are needed

Splicing• Alternate RNA splicing

– Splicing can occur in more than 1 way– Different mRNA from same RNA transcript

DNA

RNAtranscript

mRNA

Exons

or

RNA splicing

Figure 11.7

Page 20: Gene Expression Ch 11. Gene expression Genes to proteins –Genotype to phenotype Produce specific proteins when and where they are needed

Small RNA’s

• miRNA

• RNA interferencemiRNA

1

Translation blockedORmRNA degraded

Target mRNA

Protein

miRNA-proteincomplex2

34

Page 21: Gene Expression Ch 11. Gene expression Genes to proteins –Genotype to phenotype Produce specific proteins when and where they are needed

Regulation of translation• Breakdown of mRNA

• Initiation of translation

• Protein activation

• Protein breakdown

Folding ofpolypeptide andformation ofS—S linkages

Initial polypeptide(inactive)

Folded polypeptide(inactive)

Cleavage

Page 22: Gene Expression Ch 11. Gene expression Genes to proteins –Genotype to phenotype Produce specific proteins when and where they are needed

Cascades

• Protein products from one set of genes activate another set

• Homeotic gene

Egg cellwithin ovarianfollicle

Follicle cells

“Head”mRNA

Proteinsignal

Gene expression1

Cascades ofgene expression

2

Embryo Bodysegments

Adult fly

Gene expression

3

4

Egg cell

Page 23: Gene Expression Ch 11. Gene expression Genes to proteins –Genotype to phenotype Produce specific proteins when and where they are needed

Signal transduction pathways

• Series of molecular changes that converts signal on cell surface to specific response inside cell

Signaling cellSignalmolecule

Receptorprotein

Plasmamembrane

Target cellRelayproteins

Transcription factor(activated)

Transcription

Nucleus

DNA

mRNA

Newprotein

Translation

1

2

3

4

5

6

Figure 11.14

Page 24: Gene Expression Ch 11. Gene expression Genes to proteins –Genotype to phenotype Produce specific proteins when and where they are needed

Cloning• A clone is an individual created by asexual

reproduction and thus is genetically identical to a single parent

Page 25: Gene Expression Ch 11. Gene expression Genes to proteins –Genotype to phenotype Produce specific proteins when and where they are needed

Cloning• Regeneration

• Nuclear Transplantation– Reproductive and Therapeutic cloning

Remove nucleusfrom egg cell

Add somatic cellfrom adult donor

Grow in culture to produce anearly embryo (blastocyst)

Implant blastocyst insurrogate mother

Remove embryonic stemcells from blastocyst andgrow in culture

Induce stem cells toform specialized cells(therapeutic cloning)

Clone of donor is born(reproductive cloning)

Donorcell

Nucleus fromdonor cell

Figure 11.10

Page 26: Gene Expression Ch 11. Gene expression Genes to proteins –Genotype to phenotype Produce specific proteins when and where they are needed

Reproductive Cloning

• Not exact copy– Behavioral differences

• Ethical questions

Page 27: Gene Expression Ch 11. Gene expression Genes to proteins –Genotype to phenotype Produce specific proteins when and where they are needed

Therapeutic Cloning

• Medical potential

• Embryonic stem cells

• Adult stem cells– Replace non-

reproducing specialized cells as needed

– Only give rise to certain tissues

Adult stemcells in bone

marrow

Culturedembryonicstem cells

Different cultureconditions

Heart muscle cells

Different types ofdifferentiated cells

Nerve cells

Blood cells

Figure 11.12

Page 28: Gene Expression Ch 11. Gene expression Genes to proteins –Genotype to phenotype Produce specific proteins when and where they are needed

Cancer

• Divide uncontrollably – Mutations whose protein products affect the

cell cycle

• Oncogene– Can cause cancer when present in a single

copy

Page 29: Gene Expression Ch 11. Gene expression Genes to proteins –Genotype to phenotype Produce specific proteins when and where they are needed

Cancer• Proto-oncogene

– Gene that has potential to become oncogene

– Mutation or virus

Proto-oncogene DNA

Mutation withinthe gene

Multiple copiesof the gene

Gene moved tonew DNA locus,

under new controls

Oncogene New promoter

Hyperactivegrowth-stimulatingprotein innormalamount

Normal growth-stimulatingproteinin excess

Normal growth-stimulatingproteinin excess

Figure 11.16A

Page 30: Gene Expression Ch 11. Gene expression Genes to proteins –Genotype to phenotype Produce specific proteins when and where they are needed

Cancer• Tumor-suppressor

genes– Help prevent

uncontrolled growth

Tumor-suppressor gene Mutated tumor-suppressor gene

Normalgrowth-inhibitingprotein

Cell divisionunder control

Defective,nonfunctioningprotein

Cell division notunder control

Figure 11.16B

Page 31: Gene Expression Ch 11. Gene expression Genes to proteins –Genotype to phenotype Produce specific proteins when and where they are needed

Oncogene proteins and faulty tumor-suppressor proteins can interfere with normal signal transduction pathways

Growthfactor

Target cell

Receptor

Hyperactiverelay protein(product ofras oncogene)issues signalson its own

Normal productof ras gene

Relayproteins

Transcription factor(activated)

DNA

Nucleus Transcription

TranslationProtein thatstimulatescell division

Figure 11.17A

Growth-inhibitingfactor

Receptor

Nonfunctional transcriptionfactor (product of faulty p53tumor-suppressor gene)

Relayproteins

Transcription factor(activated)

Transcription

Translation

Protein thatinhibitscell division

cannot triggertranscription

Protein absent(cell divisionnot inhibited)

Normal productof p53 gene

Figure 11.17B

Page 32: Gene Expression Ch 11. Gene expression Genes to proteins –Genotype to phenotype Produce specific proteins when and where they are needed

Cancer• Series of genetic changes

– Colon cancer

Colon wall

Cellularchanges:

DNAchanges:

1

Increasedcell division

Oncogeneactivated

2

Growth of polyp

Tumor-suppressorgene inactivated

3

Growth of malignanttumor (carcinoma)

Second tumor-suppressor geneinactivated

Page 33: Gene Expression Ch 11. Gene expression Genes to proteins –Genotype to phenotype Produce specific proteins when and where they are needed

Cancer• Series of mutations

Chromosomes

mutation

1 2 3 4mutations mutations mutations

Normalcell

Malignantcell

Figure 11.18B

Page 34: Gene Expression Ch 11. Gene expression Genes to proteins –Genotype to phenotype Produce specific proteins when and where they are needed

Table 11.20