chapter 11 the control of gene expression. to clone or not to clone...
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Chapter 11
The Control of Gene Expression
To Clone or Not to Clone
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- Began in 1950’s- Dolly (1997)- proposed for endangered species- may create new problems
stop work on habitat preservationdoes not increase genetic diversityclones animals are less healthy
Gene regulation is important for the well-being of all organisms *How are genes regulated *applications *gene regulation and embryonic development
Gene Regulation Gene expression Early
understanding of gene control
Came from studies of the bacterium
Escherichia coli
In prokaryotes, genes for related enzymes
Are often controlled together in units operons
Lac Operon Can be turned on and off according to
the environmental circumstances: availability of lactose
Lac Operon
Lack of substrate inactivates the enzyme
Lac Operon
Substrate presence inactivates the repressor of the gene
Other Kinds of Operons trp operon similar to the lac operon, but functions
somewhat differently
Inactive repressor
TryptophanLactose
Active repressorPromoter Operator Genes Promoter Operator Genes
Lac Operon trp operon
Differentiation yields a variety of cell types, each
expressing a different combination of genes
multicellular eukaryotes cells become specialized as a zygote
develops into a mature organism
Muscle Pancreas Blood
Genetic Potential Differentiated cells may retain all of their
genetic potential Most differentiated cells retain a
complete set of genes
root cell cultured cell division plantlet adult plantin nutrient medium in culture
single cell
tissue
DNA Packing DNA packing in
eukaryotic chromosomes helps regulate gene expression
A chromosome contains DNA
Wound around clusters of histone proteins, forming a string of beadlike nucleosomes
Inactive Chromosomes In female mammals, one X chromosome is inactive in
each cell An extreme example of DNA packing in interphase cells X chromosome inactivation in the cells of female
mammalsEarly embryo cells of adult cat
X chromosome
Allele for orange fur
Allele for black fur
Cell division and randomInactivation of X chromosome
active
active
inactive
Control of Eukaryotic Transcription
A variety of regulatory proteins interact with DNA and with each other
Known as transcription factors “Default” state seems to be “off” They turn the transcription of genes
on or off Only a small percentage of the genes
Transcription Factors Assist in initiating eukaryotic transcription
Enhancers Promoter gene
Transcription Factors
Activatorprotein
OtherProteins
RNA polymerase
Bending of DNA
Transcription
Coordinating Eukaryotic Gene Expression
Coordinated gene expression in eukaryotes
Seems to depend on the association of enhancers with groups of genes
Eukaryotic RNA May be spliced in more than one way After transcription, alternative splicing May generate two or more types of mRNA from the
same transcript
DNA
EXONS
RNA transcript
mRNA
RNA splicing allows more than one type of polypeptide from a single gene
Introns are removed
Regulation Translation and later stages of
gene expression are also subject to regulation
After eukaryotic mRNA is fully processed and transported to the cytoplasm
There are additional opportunities for regulation
1. Breakdown of mRNA
lifetime of an mRNA molecule Short-lived mRNA: bacteria Long-lived mRNA: eukaryotes
Helps determine how much protein ismade
Example of Long-lived mRNA
Red blood cells of reptiles, amphibians and fish
Manufactures hemoglobin Last the same as the lifetime of
the RBC
2. Initiation of Translation
Control of the starting point of polypeptide synthesis
Example synthesis of Hemoglobin Iron in the heme group has to be
present
3. Protein Activation After translation is complete Polypeptides may require an alteration to become
functional
Inactive polypeptide folded polypeptide active form of insulin
SH
SH
HS
SHHS
SHSS
S S
SS
Folding of polypeptide
Formation of S-S linkage
Cleavage SS
SS
S S
Insulin
4. Protein Breakdown
Occurs in some of the proteins that trigger metabolic changes in cells
Are broken down within a few minutes or hours
Allows cell to adjust the kinds and amounts of proteins in response to the environment
Review
Multiple mechanisms regulate geneexpression in eukaryotes
Animal Cloning Nuclear transplantation can be used to
clone animals and/or therapeutic use
Removenucleus fromegg
Add somaticcell from adult
Grow in culture to producean early embryo (blastocyst)
Nucleus from donor
Surrogate mother clone of donorwith implantedblastocyst
Remove embryonic stem cells from blastocyst and growin culture
Induce stem cellsto form speciali-zed cells (therapeutic)
Connection: Reproductive Cloning Reproductive cloning has valuable
applications, but human reproductive cloning raises ethical issues
Reproductive cloning of nonhuman mammals is useful in research, agriculture, and medicine
Connection: Therapeutic Cloning can produce stem cells with great medical potential Like embryonic stem cells, adult stem cells can
perpetuate themselves in culture and give rise to differentiated cells
Adult stem cell in bonemarrow
Cultured embryonic stem cells
Different culture conditions
Different types ofDifferentiated cells
Blood cells
Nerve cells
Muscle cells
Genetic Control of Embryonic Development Cascades of gene expression and cell-to-cell
signaling direct the development of an animal Early understanding of the relationship
between gene expression and embryonic development
Came from studies of mutants of the fruit fly Drosophila melanogasterNormal Mutant
antenna
leg
D. melanogaster 1. egg protein signals follicle cells 2. follicle cells signal back to the
egg 3. egg responds localizing
specific mRNA which indicates the localization of the fly’s head
4. regulatory protein is produced 5. other proteins are also
produced and form a gradient 6. segmentation occurs 7. adult fly is the final product
1
2
3
4
5
6
7
Follicle cells
mRNA
Regulatory proteins
segmentation
ADULT
EGG
LARVA
PUPA
Signal Transduction Pathways Convert messages
received at the cell surface to responses within the cell
Signaling cell
Signaling molecule
Receptor protein
Target cell
12
3
4
5
6
Relay proteins
Transcription factor
Nucleus
DNA
Transcription
mRNA
Translation
New Protein
Key Developmental Genes are very ancient Homeotic genes contain
nucleotide sequences, called homeoboxes
That are very similar in many kinds of organisms
Fruit fly embryo (10h) mouse embryo (12d)
Adult fruit fly adult mouse
THE GENETIC BASIS OF CANCER
Cancer results from mutations in genesthat control cell division
divide uncontrollably Result from mutations in genes
whose protein products affect the cell cycle
Proto-Oncogenes A mutation can change a proto-
oncogene (a normal gene that promotes cell division) into an oncogene, which causes cells to divide excessively
Proto-oncogene DNA
Mutation within gene Normal Gene at other locus
oncogene
Hyperactive growth-stimulating protein innormal amount
Normal growth-stimulating protein in excess
New promoter
Onkos= tumor
Tumor-Suppressor Genes Mutations that inactivate tumor suppressor genes Have similar effects as oncogenes
Tumor-suppressor gene Mutated tumor-suppressor gene
Normal growth-inhibiting protein Defective, nonfunctional protein
Cell division under control Cell division not under control
Interference with Normal Signal Transduction Pathways Oncogene
proteins Can stimulate
signal transduction pathways
Growth factor
receptor
Target cell
Hyperactiverelay proteinIssues signals on
its own
Normal product
Relay proteins
Transcription factor(activated)
transcription
DNA
translation
Protein that stimulatesCell division
Interference… Faulty tumor-suppressor
proteins Can inhibit signal
transduction pathways
Growth inhibitingfactor
receptor
Relay proteinNonfunctional transcriptionFactor: cannot trigger transcription
Normal product ofP53 gene
Transcription factor(activated)
transcription
translation
Protein thatinhibits celldivision Lack of such
protein
Development of Cancer
Multiple genetic changes underlie thedevelopment of cancer
Cancers result from a series of genetic changes in a cell lineage
Colon cancer Develops in a stepwise fashion
Cellular changes Increased cell division growth of a polyp Growth of a malignant tumor (carcinoma)
DNA changes Oncogene activated Tumor-suppressor gene inactivated 2nd tumor-suppressor gene inactivated
1 2 3
Accumulation of mutations Can lead to
cancer
Chromosomes 1 mutation 2 mutations 3 mutations 4 mutations
Normal cell Malignant cell
Talking about Science Mary-Claire King discusses mutations
thatcause breast cancer
Researchers have gained insight into thegenetic basis of breast cancer
By studying families in which a diseasepredisposing
mutation is inherited
Avoiding carcinogens can reduce the risk of cancer Reducing exposure to carcinogens
(which induce cancer-causing mutations)
And making other lifestyle choices canhelp reduce cancer risk
Cancer in the U.S.
The End
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