1. CONTROL OF GENE EXPRESSION
© 2012 Pearson Education, Inc. 1

2. Proteins Interact with DNA to turn Prokaryotic Genes On or Off In Response to Environmental Changes
Gene regulation is the turning on and off of genes
Gene expression is the overall process of information flow from genes to proteins. 2

3. Proteins Interact with DNA to turn Prokaryotic Genes On or Off In Response to Environmental Changes
When an E. coli encounters lactose, all enzymes needed for its metabolism are made at once using the lactose operon.
The lactose (lac) operon includes
Three adjacent lactose-utilization genes
A promoter sequence where RNA pol. binds and initiates transcription of all three lactose genes
An operator sequence where a repressor can bind and block RNA polymerase action.
A cluster of genes with related functions, and its control sequences, is called an operon.
Found mainly in prokaryotes. 3

4. Proteins Interact with DNA to turn Prokaryotic Genes On or Off In Response to Environmental Changes
Regulation of the lac operon
Regulated by a regulatory gene that codes for a repressor protein
the regulatory gene is outside of the operon and is always being transcribed & translated
When lactose is absent: the repressor protein binds the operator preventing transcription
When lactose is present: it inactivates the repressor protein so,
the operator is unblocked
RNA pol. can bind the promoter
all three genes of operon are transcribed 4

5. Operon turned off (lactose is absent): OPERON Regulatory gene
Promoter
Operator
Lactose-utilization genes
DNA
mRNA
RNA polymerase cannot attach to the promoter
Protein
Active repressor
Operon turned on (lactose inactivates the repressor):
Figure 11.1B The lac operon
DNA
RNA polymerase is bound to the promoter
mRNA
Translation
Protein
Inactive repressor
Lactose
Enzymes for lactose utilization 5

6. Multiple Mechanisms Regulate Gene Expression in Eukaryotes
These control points include:
Chromosome changes and DNA unpacking
Control of transcription
Control of RNA processing including the
addition of a cap and tail, RNA splicing
Flow through the nuclear envelope
Breakdown of mRNA
Control of translation
Control after translation
cleavage/modification/activation of proteins
protein degradation
Multiple control points exist in Eukaryotic gene expression
Genes can be turned on or off, or sped up, or slowed down. 6

7. DNA unpacking Other changes to the DNA
Chromosome
Chromosome
DNA unpacking Other changes to the DNA
DNA
Gene
Gene
Transcription
Exon
RNA transcript
Intron
Addition of a cap and tail
Figure 11.7_1 The gene expression “pipeline” in a eukaryotic cell (part 1)
Splicing
Tail
Cap
mRNA in nucleus
Flow through nuclear envelope
NUCLEUS
CYTOPLASM 7

8. Cleavage, modification, activation
Figure 11.7_2
CYTOPLASM
mRNA in cytoplasm
Breakdown of mRNA
Broken- down mRNA
Translation
Polypeptide
Polypeptide
Cleavage, modification, activation
Active protein
Active protein
Figure 11.7_2 The gene expression “pipeline” in a eukaryotic cell (part 2)
Breakdown of protein
Amino acids 8

9. DNA double helix (2-nm diameter)
Chromosome Structure and Chemical Modifications can Affect Gene Expression
DNA packing: Eukaryotic chromosomes undergo multiple levels of folding and coiling
Nucleosomes = DNA wrapped around histone proteins.
Nucleosomes appear as “beads on a string”.
At the next level of packing, the beaded string is wrapped into a tight helical fiber (30nm).
This fiber coils further into a thick supercoil (300nm).
Looping and folding further compacts DNA into a metaphase chromosome
DNA double helix (2-nm diameter)
(30-nm)
(300-nm)
700 nm 9

10. Highly compacted chromatin is generally not expressed
Chromosome Structure and Chemical Modifications can Affect Gene Expression
DNA packing can prevent gene expression by preventing RNA polymerase & other proteins from contacting DNA.
Cells seem to use higher levels of packing for long-term inactivation of genes.
Highly compacted chromatin is generally not expressed 10

11. Epigenetic inheritance
Chromosome Structure and Chemical Modifications can Affect Gene Expression
Epigenetic inheritance
Inheritance of traits transmitted by mechanisms that do not alter the sequence of nucleotides in DNA
Chemical modification of DNA bases or histone proteins can result in epigenetic inheritance
Methylation (adding methyl groups (CH3) to DNA) prevents its’ expression
Removal of the extra methyl groups can turn on some of these genes 11

12. X-chromosome inactivation
Chromosome Structure and Chemical Modifications can Affect Gene Expression
X-chromosome inactivation
In female mammals either the maternal or paternal chromosome is randomly inactivated (inactivated X chromosome = Barr body)
This occurs early in embryonic development; all cells that arise from this cell have the same inactivated X chromosome.
Ex. Tortoiseshell fur coloration is due to inactivation of X chromosomes in heterozygous female cats. 12

13. Cell division and random X chromosome inactivation
Early Embryo
Adult
Two cell populations
Cell division and random X chromosome inactivation
X chromo- somes
Active X
Orange fur
Inactive X
Figure 11.2B A tortoiseshell pattern on a female cat, a result of X chromosome inactivation
Allele for orange fur
Inactive X
Allele for black fur
Active X
Black fur 13

14. Complex Assemblies of Proteins Control Eukaryotic Transcription
Eukaryotes use regulatory proteins called transcription factors to regulate transcription
Transcription factors can be activators or repressors
Activator proteins
Bind to DNA sequences called enhancers.
Next, DNA is bent by a DNA bending protein, bringing bound activators closer to the promoter.
Activators interact with other transcription factors at the promoter allowing RNA pol to bind and transcribe the gene 14

15. Transcription factors
Enhancers
Promoter
Gene
DNA
Activator proteins
Transcription factors
Other proteins
RNA polymerase
Figure 11.3 A model for the turning on of a eukaryotic gene
Bending of DNA
Transcription 15

16. Later Stages of Gene Expression are Subject to Regulation
Breakdown of mRNA
Enzymes in the cytoplasm destroy mRNA
Long-lived mRNAs can be translated into many more protein molecules than short-lived ones
mRNA’s of eukaryotes have lifetimes from hours to weeks

17. Later Stages of Gene Expression are Subject to Regulation
A significant amount of the genome codes for microRNAs
microRNAs (miRNAs) can bind to complementary sequences on mRNA molecules. This can lead to
degradation of the target mRNA
blocking its translation
RNA interference (RNAi) is the use of miRNA to control gene expression
miRNAs can be injected into a cell to turn off a specific gene sequence. 17

18. miRNA- protein complex1
miRNA- protein complex 2
Target mRNA
Figure 11.5 Mechanisms of RNA interference 3 or 4
Translation blocked
mRNA degraded 18

19. Later Stages of Gene Expression are Subject to Regulation
Protein Activation- After translation is complete some proteins require alterations before they are fully function SH SH
Folding of the polypeptide and the formation of S—S linkages S S S S
Cleavage SH S S SH SH S S SH S S S S
Initial polypeptide (inactive)
Folded polypeptide (inactive)
Active form of insulin
Figure 11.6 Protein activation: the role of polypeptide cleavage 19

20. Later Stages of Gene Expression are Subject to Regulation
Protein Breakdown
Final control mechanism
Cells can adjust the kinds and amounts of its proteins in response to environmental changes
Damaged proteins are usually broken down right away and replaced

21. CLONING OF PLANTS AND ANIMALS
© 2012 Pearson Education, Inc. 21

22. Plant cloning shows that differentiated cells may retain all of their genetic potential
Most differentiated cells retain a full set of genes, even though only a subset may be expressed. Evidence is available from
plant cloning, in which a root cell can divide to form an adult plant
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23. Root cells cultured in growth medium Cell division in culture
Root of carrot plant
Single cell
Figure Growth of a carrot plant from a differentiated root cell
Root cells cultured in growth medium
Cell division in culture
Plantlet
Adult plant 23

24. Nuclear transplantation Can be Used to Clone Animals
Animal cloning can be achieved using nuclear transplantation: the nucleus of an egg cell is replaced with a nucleus from an adult somatic cell.
Using nuclear transplantation to produce new organisms is called reproductive cloning (first used in mammals in 1997 to produce Dolly)
Reproductive cloning is used to produce animals with desirable traits to
produce better agricultural products
produce therapeutic agents
restock populations of endangered animals 24

25. The nucleus is removed from an egg cell.
Donor cell
Nucleus from
the donor cell
Blastocyst
The nucleus is removed from an egg cell.
A somatic cell from an adult donor is added.
The cell grows in culture to produce an early embryo (blastocyst).
Figure 11.13_1 Nuclear transplantation for cloning (part 1) 25

26. The blastocyst is implanted in a surrogate mother.
Reproductive cloning
Blastocyst
The blastocyst is implanted in a surrogate mother.
A clone of the donor is born.
Therapeutic cloning
Figure 11.13_2 Nuclear transplantation for cloning (part 2)
Embryonic stem cells are removed from the blastocyst and grown in culture.
The stem cells are induced to form specialized cells. 26

28. Nuclear transplantation Can be Used to Clone Animals
A blastocyst made through nuclear transplantation provides embryonic stem (ES) cells. This procedure can be used to produce
cell cultures for research
stem cells for therapeutic treatments as in therapeutic cloning 28

29. Stem Cells When grown in laboratory culture, embryonic stem cells
When grown in laboratory culture, embryonic stem cells
can divide indefinitely
can give rise to many types of differentiated cells
are more promising than adult stem cells
Adult stem cells can give rise to many, but not all, types of cells 29

30. Adult stem cells in bone marrow Cultured embryonic stem cells
Blood cells
Adult stem cells in bone marrow
Nerve cells
Cultured embryonic stem cells
Figure Differentiation of stem cells in culture
Heart muscle cells
Different culture conditions
Different types of differentiated cells 30

31. Reproductive Cloning has Valuable Applications, but Human Reproductive Cloning Raises Ethical Issues
Since Dolly’s landmark birth in 1997, researchers have cloned many other mammals, including mice, cats, horses, cows, mules, pigs, rabbits, ferrets, and dogs.
Cloned animals can show differences in anatomy and behavior due to
environmental influences
random phenomena
© 2012 Pearson Education, Inc. 31

32. THE GENETIC BASIS OF CANCER
© 2012 Pearson Education, Inc. 32

33. Cancer Results from Mutations in Genes that Control Cell Division
Mutations in two types of genes can cause cancer.
Oncogenes
Oncogenes are cancer causing genes produced when a normal proto-oncogene is mutated
Proto-oncogenes are normal genes that code for proteins that affect the cell cycle.
Tumor-suppressor genes
Tumor-suppressor genes normally inhibit cell division or function in the repair of DNA damage.
Mutations inactivate TS genes and allow uncontrolled division to occur.
© 2012 Pearson Education, Inc. 33

34. Proto-oncogene (for a protein that stimulates cell division)
DNA
A mutation within the gene
Multiple copies of the gene
The gene is moved to a new DNA locus, under new controls
Oncogene
New promoter
Figure 11.16A Alternative ways to make oncogenes from a proto-oncogene (all leading to excessive cell growth)
Hyperactive growth- stimulating protein in a normal amount
Normal growth- stimulating protein in excess
Normal growth- stimulating protein in excess 34

35. Tumor-suppressor gene Mutated tumor-suppressor gene
Normal growth- inhibiting protein
Defective, nonfunctioning protein
Cell division not under control
Cell division under control
Figure 11.16B The effect of a mutation in a tumor-suppressor gene 35

36. An oncogene is activated A tumor-suppressor gene is inactivated
DNA changes:
An oncogene is activated
A tumor-suppressor gene is inactivated
A second tumor- suppressor gene is inactivated
Cellular changes:
Increased cell division
Growth of a polyp
Growth of a malignant tumor 1 2 3
Figure 11.17A Stepwise development of a typical colon cancer
Colon wall 36

37. 1 mutation 2 mutations 3 mutations 4 mutations Chromosomes Normal cell
Figure 11.17B
1 mutation
2 mutations
3 mutations
4 mutations
Chromosomes
Normal cell
Malignant cell
Figure 11.17B Accumulation of mutations in the development of a cancer cell 37

38. Lifestyle Choices Can Reduce the Risk of Cancer
After heart disease, cancer is the second-leading cause of death in most industrialized nations.
Cancer can run in families if an individual inherits an oncogene or a mutant allele of a tumor-suppressor gene that makes cancer one step closer.
Most cancers cannot be associated with an inherited mutation. 38

39. Lifestyle Choices Can Reduce the Risk of Cancer
Carcinogens are cancer-causing agents that alter DNA.
Most mutagens (substances that promote mutations) are carcinogens.
The one substance known to cause more cases and types of cancer than any other single agent is tobacco smoke. 39