1. The Control of Gene Expression
Chapter 11
The Control of Gene Expression

2. To Clone or Not to Clone?
A clone is an individual created by asexual reproduction and thus is genetically identical to a single parent
Cloning an animal using a transplanted nucleus shows that an adult somatic cell contains a complete genome
Cloning has potential benefits but evokes many concerns
Does not increase genetic diversity
May produce less healthy animals

4. GENE REGULATION
11.1 Proteins interacting with DNA turn prokaryotic genes on or off in response to environmental changes
Gene regulation is the "turning on" and "turning off" of genes
Helps organisms respond to environmental changes
Gene expression is the process by which information flows from genes to protein
Early understanding of gene control came from studies of the bacterium Escherichia coli

6. An operon is a cluster of genes with related functions, along with two control sequences
Promoter: A sequence of genes where the RNA polymerase attaches and initiates transcription
Operator: A sequence of genes between the operon and the promoter that acts as a switch for the binding of RNA polymerase
A repressor binds to the operator, stopping transcription
A regulatory gene, located outside the operon, codes for the repressor

7. The lac operon contains the genes that code for the enzymes that metabolize lactose
Repressor is active when alone and inactive when bound to lactose
The trp operon allows bacteria to stop making tryptophan when it is already present
Repressor is inactive alone; must bind to the amino acid tryptophan to be active
A third type of operon uses activators, proteins that turn operons on by binding to DNA

8. Lactose-utilization genes
LE 11-1b
OPERON
Regulatory
gene
Promoter
Operator
Lactose-utilization genes
DNA
mRNA
RNA polymerase
cannot attach to
promoter
Active
repressor
Protein
Operon turned off (lactose absent)
DNA
RNA polymerase
bound to promoter
mRNA
Protein
Inactive
repressor
Enzymes for lactose utilization
Lactose
Operon turned on (lactose inactivates repressor)

9. LE 11-1c Promoter Operator Genes DNA Active repressor Active repressor
Tryptophan
Inactive
repressor
Inactive
repressor
Lactose
lac operon
trp operon

10. 11.2 Differentiation yields a variety of cell types, each expressing a different combination of genes
Gene regulation is much more complex in eukaryotes than in prokaryotes
In multicellular eukaryotes, cells become specialized as a zygote develops into a mature organism
The particular genes that are active in each type of cell are the source of its particular function

11. Muscle cell Pancreas cells Blood cells

12. 11.3 Differentiated cells may retain all of their genetic potential
Though differentiated cells express only a small percentage of their genes, they retain a complete set of genes
Allows for propagation of crop plants
In animal cells can lead to regeneration

13. LE 11-3
Root of
carrot plant
Single cell
Root cells cultured
in nutrient medium
Cell division
in culture
Plantlet
Adult plant

14. 11.4 DNA packing in eukaryotic chromosomes helps regulate gene expression
DNA can fit into a chromosome because of packing
DNA winds around clusters of histone proteins, forming a string of bead-like nucleosomes
The beaded fiber coils, supercoils, and further folds into chromosomes
DNA packing prevents gene expression most likely by preventing transcription proteins from contacting the DNA

15. Animation: DNA Packing
LE 11-4
DNA double
helix (2-nm
diameter)
Histones
Linker
“Beads on
a string”
TEM
Nucleosome
(10-nm diameter)
Tight helical fiber
(30-nm diameter)
Supercoil
(300-nm
diameter)
TEM
700 nm
Metaphase chromosome
Animation: DNA Packing

16. 11.5 In female mammals, one X chromosome is inactive in each cell
An extreme example of DNA packing is X chromosome inactivation in interphase cells of female mammals
In each cell line, the X chromosome from either parent may be inactivated
Leads to a random mosaic of expression of the two X chromosomes
Example: coat color in tortoiseshell cat

17. LE 11-5 Early embryo Two cell populations in adult Cell division
and random
X chromosome
inactivation
Active X
Orange
fur
X chromosomes
Inactive X
Inactive X
Allele for
orange fur
Active X
Black fur
Allele for
black fur

18. 11.6 Complex assemblies of proteins control eukaryotic transcription
A variety of regulatory proteins interact with DNA and with each other to turn eukaryotic genes on or off
In contrast to bacteria
Each eukaryotic gene has its own promoter and control sequences
Activators are more important than repressors

19. Animation: Initiation of Transcription
Eukaryotic RNA polymerase needs the assistance of transcription factors
The binding of activators to enhancers initiates transcription
Silencers inhibit the start of transcription
Coordinated gene expression in eukaryotes seems to depend on the association of specific enhancers with groups of genes
Animation: Initiation of Transcription

20. LE 11-6 Enhancers Promoter Gene DNA Activator proteins Transcription
factors
Other
proteins
RNA polymerase
Bending
of DNA
Transcription

21. Animation: RNA Processing
11.7 Eukaryotic RNA may be spliced in more than one way
After transcription, splicing removes noncoding introns
Alternative splicing may generate two or more types of mRNA from the same transcript
Exons or
RNA splicing
mRNA
RNA
transcript
DNA
Animation: RNA Processing

22. 11.8 Translation and later stages of gene expression are also subject to regulation
After eukaryotic mRNA is processed and transported to the cytoplasm, there are additional opportunities for regulation
Breakdown of mRNA: The lifetime of an mRNA molecule helps determine how much protein is made
Initiation of translation: A great many proteins control the start of polypeptide synthesis

23. Protein activation: After translation, polypeptides may be cut into smaller, active products
Protein breakdown: Rapid selective breakdown of proteins allows the cell to respond to environmental changes SH
Initial polypeptide
(inactive)
Folded polypeptide
Active form
of insulin
Cleavage
Folding of polypeptide and
formation of S—S linkages HS
S-S

24. 11.9 Review: Multiple mechanisms regulate gene expression in eukaryotes
Cellular differentiation results from selective turning on or off of genes at multiple control points
In nucleus
DNA unpacking and other changes
Transcription
Addition of cap and tail
Splicing

25. Each differentiated cell still retains its full genetic potential
In cytoplasm
Breakdown of mRNA
Translation
Cleavage/modification/activation
Breakdown of protein
Each differentiated cell still retains its full genetic potential

26. LE 11-9 NUCLEUS CYTOPLASM Chromosome DNA unpacking
Other changes to DNA
Gene
Transcription
Gene
Exon
RNA transcript
Intron
Addition of cap and tail
Splicing
Tail
mRNA in nucleus
Cap
Flow through
nuclear envelope
mRNA in cytoplasm
CYTOPLASM
Breakdown of mRNA
Broken-
down
mRNA
Translation
Polypeptide
Cleavage / modification /
activation
Active protein
Breakdown
of protein
Broken-
down
protein

27. 11.10 Nuclear transplantation can be used to clone animals
ANIMAL CLONING
11.10 Nuclear transplantation can be used to clone animals
Nuclear transplantation
Nucleus of a somatic cell is transplanted into a surrogate egg stripped of nucleus
Cell divides to the blastocyst stage
Reproductive cloning
Blastocycst is implanted into uterus
Live animal is born

28. Embryonic stem cells are harvested from blastocyst
Therapeutic cloning
Embryonic stem cells are harvested from blastocyst
These cells give rise to all the specialized cells of the body
Donor
cell
Nucleus from
donor cell
Remove nucleus
from egg cell
Add somatic cell
from adult donor
Grow in culture to produce an
early embryo (blastocyst)
Implant blastocyst in
surrogate mother
Remove embryonic stem
cells from blastocyst and
grow in culture
Clone of donor is born
(reproductive cloning)
Induce stem cells to
form specialized cells
(therapeutic cloning)

29. CONNECTION
11.11 Reproductive cloning has valuable applications, but human reproductive cloning raises ethical issues
Reproductive cloning of nonhuman mammals is useful in research, agriculture, and medicine
There are many obstacles, both practical and ethical, to human cloning
Research continues in the absence of consensus

30. CONNECTION
11.12 Therapeutic cloning can produce stem cells with great medical potential
In culture, embryonic stem cells
Can give rise to all cell types in the body
Must be obtained from human embryos
Adult stem cells
Can give rise to many, but perhaps not all, cell types
Are present in adult tissues and, thus, are less controversial than embryonic cells

31. Adult stem cells in bone marrow Cultured embryonic stem cells
LE 11-12
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

32. THE GENETIC CONTROL OF EMBRYONIC DEVELOPMENT
11.13 Cascades of gene expression and cell-to-cell signaling direct the development of an animal
Studies of mutant fruit flies led to early understanding of gene expression and embryonic development
Before fertilization, communication between the egg and adjacent cells determines body polarity
A cascade of gene expression controls development of an animal from a fertilized egg
Master control homeotic genes regulate batteries of genes that shape anatomical parts

33. Head of a normal fruit fly Head of a developmental mutant
LE 11-13a
Eye
Antenna
Leg
Head of a normal fruit fly
Head of a developmental mutant

34. LE 11-13b Egg cell within ovarian follicle Egg cell Egg protein
signaling
follicle cells
Follicle cells
Gene expression
in follicle cells
Follicle cell
protein
signaling
egg cell
Localization of
“head” mRNA
“Head”
mRNA
Fertilization and mitosis
Embryo
Translation of
“head” mRNA
Gradient of
regulatory
protein
Gene expression
Gradient of
certain other
proteins
Gene expression
Body
segments
0.1 mm
Larva
Gene expression
Adult fly
Head end
Tail end
0.5 mm

35. 11.14 Signal transduction pathways convert messages received at the cell surface to responses within the cell
Signal transduction pathway
Signaling cell secretes signal molecules
Signal molecules bind to receptors on target cell's plasma membrane
Cascade of events leads to the activation of a specific transcription factor

36. Transcription factor triggers transcription of a specific gene
Translation of the mRNA produces a protein

37. Animation: Overview of Cell Signaling
Signaling cell
Signal
molecule
Receptor
protein
Plasma
membrane
Target cell
Nucleus
Transcription factor
(activated)
Relay
proteins
DNA
mRNA
Transcription
Translation
New
Animation: Overview of Cell Signaling
Animation: Signal Transduction Pathways
Animation: Cell Signaling

38. 11.15 Key developmental genes are ancient
Homeotic genes contain nucleotide sequences called homeoboxes
Regulate gene expression during development
Similarity of homeoboxes among organisms suggests a very early evolutionary origin

39. Fruit fly embryo (10 hours)
LE 11-15
Fly chromosome
Mouse chromosomes
Mouse chromosomes
Fruit fly embryo (10 hours)
Mouse embryo (12 days)
Adult fruit fly
Adult mouse

40. THE GENETIC BASIS OF CANCER
11.16 Cancer results from mutations in genes that control cell division
An oncogene can cause cancer when present in a single copy in a cell
A cell can acquire an oncogene from
A virus
A mutation in a proto-oncogene, a normal gene with the potential to become an oncogene

41. LE 11-16a
Proto-oncogene DNA
Mutation within
the gene
Multiple copies
of the gene
Gene moved to
new DNA locus,
under new controls
Oncogene
New promoter
Hyperactive
growth-
stimulating
protein in
normal
amount
Normal growth-
stimulating
protein
in excess
Normal growth-
stimulating
protein
in excess

42. Tumor-suppressor genes
Normally code for proteins that inhibit cell division
When inactivated by mutation, can lead to uncontrolled cell division and tumors

43. Tumor-suppressor gene Mutated tumor-suppressor gene
LE 11-16b
Tumor-suppressor gene
Mutated tumor-suppressor gene
Normal
growth-
inhibiting
protein
Defective,
nonfunctioning
protein
Cell division
under control
Cell division not
under control

44. 11.17 Oncogene proteins and faulty tumor-suppressor proteins can interfere with normal signal transduction pathways
Stimulatory signal-transduction pathway
Stimulates cell division in response to growth factor
Can be stimulated by oncogene proteins that produce hyperactive relay proteins

45. LE 11-17a Growth factor Receptor Target cell Hyperactive relay protein
(product of
ras oncogene)
issues signals
on its own
Normal product
of ras gene
Relay
proteins
Transcription factor
(activated)
DNA
Nucleus
Transcription
Translation
Protein that
stimulates
cell division

46. Inhibitory signal-transduction pathway
Inhibits cell division in response to growth-inhibiting factor
Faulty tumor-suppressor genes may produce proteins that fail to inhibit cell division

47. LE 11-17b Growth-inhibiting factor Receptor Relay proteins
Nonfunctional transcription
factor (product of faulty p53
tumor-suppressor gene)
cannot trigger
transcription
Transcription
factor (activated)
Normal product
of p53 gene
Transcription
Translation
Protein that
inhibits
cell division
Protein absent
(cell division
not inhibited)

48. 11.18 Multiple genetic changes underlie the development of cancer
Cancers result from a series of genetic changes in a cell linage
More than one somatic mutation is necessary
Accumulation of mutations over time leads to uncontrolled cell division
Example: Colon cancer develops in a stepwise fashion

49. LE 11-18a Colon wall Cellular changes: Increased cell division
Growth of polyp
Growth of malignant
tumor (carcinoma)
DNA
changes:
Oncogene
activated
Tumor-suppressor
gene inactivated
Second tumor-
suppressor gene
inactivated

50. LE 11-18b Chromosomes 1 mutation 2 mutations 3 mutations 4 mutations
Normal
cell
Malignant
cell

51. 11.19 Mary-Claire King discusses mutations that cause breast cancer
TALKING ABOUT SCIENCE
11.19 Mary-Claire King discusses mutations that cause breast cancer
Researchers have gained insight into the genetic basis of breast cancer by studying families with a history of the disease
A mutation in the gene BRCA1 can put a woman at high risk for breast cancer
Environmental influences also play a role

52. 11.20 Avoiding carcinogens can reduce the risk of cancer
CONNECTION
11.20 Avoiding carcinogens can reduce the risk of cancer
Carcinogens are agents that induce cancer-causing mutations
UV radiation, X-rays
Mutagenic chemical compounds, particularly tobacco smoke
Reducing exposure to carcinogens and making other lifestyle choices can help reduce cancer risk