1. 張學偉 生物醫學暨環境生物學系 助理教授
僅供教學使用

2. If a salamander loses a leg, it can grow a new one
Shortly after you drink a milk shake, bacteria living in your large intestine turn on certain genes
If a salamander loses a leg, it can grow a new one
Salamander蠑螈

3. Cancer-causing genes were first discovered in a chicken virus
Lung cancer causes more deaths than any other kind of cancer

4. BIOLOGY AND SOCIETY: BABY’S FIRST BANK ACCOUNT
In recent years umbilical cord and placental blood has been collected at birth.  store in liquid nitrogen
Stem
cells
Figure 11.1

5. Umbilical cord and placental blood is rich in stem cells
Stem cells can develop into a wide variety of different body cells
 Most cells of the adult lack this ability.
Figure 11.8

6. FROM EGG TO ORGANISM: HOW AND WHY GENES ARE REGULATED
Four of the many different types of human cells
They all share the same genome
What makes them different?
(a) Three muscle cells (partial)
(b) A nerve cell (partial)
(c) Sperm cells
(d) Blood cells
Genome (基因體;基因組):一個細胞中的所有遺傳物質
Figure 11.2

7. In cellular differentiation
Certain genes are turned on and off
Cells become specialized in structure and function
It is the regulation of genes that leads to this specialization.

8. Patterns of Gene Expression in Differentiated Cells
In gene expression
A gene is turned on and transcribed into RNA
Information flows from genes to proteins,
genotype to phenotype
The regulation of gene expression plays a central role in development from a zygote to a multicellular organism

9. Patterns of gene expression in specialized human cells
Pancreas cell
Eye lens cell
(in embryo)
Nerve cell
Glycolysis
enzyme
genes
Crystallin
gene
Insulin
gene
Hemoglobin
gene
Key:
Active
gene
Inactive
gene
Figure 11.3

10. DNA Microarrays: Visualizing Gene Expression
DNA microarray- is a glass slide carrying thousands of different kinds of single stranded DNA fragments arranged in an array.
Array (grid)
Glass slide 參考

11. DNA Microarrays: Visualizing Gene Expression
A DNA microarray allows visualization of gene expression 1
mRNA
isolated
Reverse transcriptase and
labeled DNA nucleotides 2
cDNA made
from mRNA
DNA microarray
(each well contains
single stranded DNA from a particular gene) 單股 單股 3
cDNA
applied to
wells 4
Unbound cDNA
rinsed away
Fluorescent
spot
Nonfluorescent
spot
cDNA
DNA of gene
DNA of gene
Figure 11.4a

12. The pattern of glowing spots on a microarray enables researchers to determine which genes are turned on or off
Figure 11.4b

13. The Genetic Potential of Cells- plant & animal
Differentiated cells
All contain a complete set of DNA
May act like other cells if their pattern of gene expression is altered
Clones- Genetically identically organisms

14. The Genetic Potential of Cells- plant
Differentiated plant cells
Have the ability to develop into a whole new organism
Root of
carrot plant
Plantlet
Cell division
in culture
Single cell
Root cells in
growth medium
Adult plant
Figure 11.5

15. The Genetic Potential of Cells- plant
The somatic cells of a single plant can be placed in a growing medium to produce clones
Clones- Genetically identically organisms

16. The Genetic Potential of Cells- animal
Regeneration
Is the regrowth of lost body parts in animals
(reverse differentiated state) Re-differentiate
If a salamander loses a leg, it can grow a new one

17. Reproductive Cloning of Animals
Nuclear transplantation
Involves replacing nuclei of egg cells with nuclei from differentiated cells
Has been used to clone a variety of animals
Scottish researchers cloned the first mammal in 1997
Dolly, the sheep

18. The procedure that produced Dolly is called reproductive cloning
reproductive cloning (individual) & therapeutic cloning (cell)
The procedure that produced Dolly is called reproductive cloning
Reproductive cloning
Donor cell
Nucleus from
donor cell
Implant embryo in
surrogate mother
Clone of donor is born
Therapeutic cloning
Remove nucleus
from egg cell
Add somatic cell from adult donor
Grow in culture
to produce an
early embryo
Remove embryonic stem cells from embryo and grow in culture
Induce stem cells to form specialized cells for therapeutic use
Figure 11.6

19. Other organisms have since been produced using this technique, some by the pharmaceutical industry
(a) Piglets
(b) Banteng
白臀野牛
Figure 11.7

20. Therapeutic Cloning and Stem Cells
Produces embryonic stem cells (ES cells)
ES cells-
are cells in an early animal embryo that differentiate during development to give rise to all the specialized cells in the body.
Development- the process from fertilized egg to embryo

21. Embryonic stem cells- Can give rise to specific types of differentiated cells
Liver cells
Cultured
embryonic
stem cells
Nerve cells
Heart muscle cells
Different culture
conditions
Different types of
differentiated cells
Figure 11.8

22. Adult stem cells
Generate replacements for nondividing differentiated cells
Are unlike ES cells, because they are partway along the road to differentiation

23. In 2001, a biotechnology company announced that it had cloned the first human embryo
Stopped at 6-cell stage
Figure 11.9

24. THE REGULATION OF GENE EXPRESSION
How is gene expression regulated in a cell?
Chromosome
Unpacking of DNA
DNA
Gene
The “pipeline” in a eukaryotic cell
Transcription of gene
Intron Exon
RNA transcript
Processing of RNA
Flow of mRNA
through nuclear
envelope
Cap
Tail
Nucleus
mRNA in nucleus
Cytoplasm
mRNA in cytoplasm
Translation of mRNA
Breakdown
of mRNA
Polypeptide
Various changes
to polypeptide
Active protein
Breakdown of protein
Figure 11.10
Broken down protein

25. Gene Regulation in Bacteria
Bacteria can alter gene expression for metabolism based on environmental factors
Control sequences
Are stretches of DNA that coordinate gene expression
An operon 操縱組
Is a cluster of genes with related functions, including the control sequences

26. A promoter 啟動子 An operator 操作子 Is a control sequence
Is the site where the transcription enzyme initiates transcription
An operator 操作子
Is a DNA sequence between the promoter and the enzyme genes [位置關係]
Acts as an on and off switch for the genes

27. The lac operon in “off” mode
Lactose absent
Operon
Regulatory gene
Promoter
Operator
Lactose-utilization genes
DNA
mRNA
RNA polymerase cannot attach to promoter
Protein
Active
repressor
(a) Operon turned off (default state when no lactose is present)
Figure 11.11a

28. The lac operon in “on” mode
Lactose present
DNA
RNA polymerase bound to promoter
mRNA
Protein
Inactive
repressor
Lactose
Enzymes for lactose utilization
(b) Operon turned on (repressor inactivated by lactose)
Figure 11.11b

29. Gene Regulation in the Nucleus of Eukaryotic Cells
Eukaryotic cells have more elaborate mechanisms of gene expression than bacteria
DNA unpacking
Transcription 核
RNA processing
RNA transport
Visual Summary 11.4

30. The Regulation of DNA Packing
Cells may use DNA packing for long-term inactivation of genes
X chromosome inactivation
Is seen in female mammals
Involves one entire X chromosome in each somatic cell being almost entirely inactive

31. Tortoiseshell pattern on a cat
Two cell populations
in adult cat:
Early embryo:
Cell division and X chromosome
inactivation
Active X
Orange fur
X chromosomes
Inactive X
隨機的
Inactive X
Active X
Black fur
Allele for
orange fur
Allele for
black fur
other
Orange/orange
black/black
Orange/orange
black/black
Figure 11.12

32. Calico cat also has white area, which are determined by another gene.
有斑點的動物[C] calico
Figure 11.12x

33. The Initiation of Transcription
The most important stage for regulating gene expression is transcription.
Eukaryotic control mechanisms
Involve regulatory proteins interact with DNA
Regulate transcription

34. Model for turning on of a eukaryotic gene
repressor
Activator
proteins
Transcription
factors
Other
proteins
RNA polymerase
Enhancers
Promoter
Gene
DNA
Bending
of DNA
Transcription
Figure 11.13

35. Repressors are less common than activators
Each eukaryotic gene
Has its own promoter and other control sequences
May have repressors, which turn genes off
May have activators, which turn genes on
Repressors are less common than activators

36. Transcription factors
Are proteins that turn on eukaryotic genes
Enhancers [DNA seq]
Are bound with activator proteins as the first step in initiating transcription
Silencers [DNA seq]
Are repressor proteins that may inhibit the start of transcription

37. The “default” state for most genes in multicellular eukaryotes seems to be “off” with the exception of “ housekeeping” genes for routine activities.

38. RNA processing includes
The eukaryotic cell
Localizes transcription in the nucleus
Processes RNA in the nucleus
RNA processing includes
The addition of a cap and tail to the RNA
The removal of any introns
The splicing together (join) of the remaining exons

39. Producing two different mRNAs from the same gene
Exons
DNA
RNA transcript
Alternative RNA splicing or
mRNA
Figure 11.14

40. Regulation in the Cytoplasm
After eukaryotic mRNA is transported to the cytoplasm, there are additional opportunities for regulation
mRNA breakdown
Translation
細胞質
Protein activation
Protein breakdown
Visual Summary 11.5

41. (nucleotides, for example)
The Breakdown of mRNA
Eukaryotic mRNAs
Can have different lifetimes
Are all eventually broken down and their parts recycled
Macromolecules
(mRNA, for example)
Synthesis
Breakdown
Monomers
(nucleotides, for example)
Figure 11.15

42. The Regulation of Translation
The process of translation
May be regulated by many different proteins

43. Post-translation control mechanisms
Protein Alterations
Post-translation control mechanisms
Occur after translation
Often involve cutting polypeptides into smaller, active final products
Cutting
Figure 11.16
Initial polypeptide
Insulin (active hormone)

44. Protein Breakdown
The selective breakdown of proteins is another control mechanism operating after translation

45. In a multicellular organism
Cell Signaling
In a multicellular organism
Gene regulation can cross cell boundaries (Cell-to-cell signaling: is a key mechanism in the development of a multicellular organism)
A cell can produce chemicals that induce another cell to be regulated a certain way

46. Signal transduction Is the main mechanism of cell-to-cell signaling 1
Signaling cell 1 1
Is the main mechanism of cell-to-cell signaling
Secretion
Signal
molecule
Plasma
membrane
Reception 2 2 3 4
Receptor
protein 3 4
Signal-transduction
pathway
Transcription factor
(activated)
Target
cell
Nucleus 5 5
Response
Tran-
scription
New protein
mRNA 6
Translation 6
Figure 11.17

47. THE GENETIC BASIS OF CANCER
Genes That Cause Cancer
As early as 1911 certain viruses were known to cause cancer
Cancer-causing viruses often carry specific genes called oncogenes
Cancer-causing genes were first discovered in a chicken virus
Rous sarcoma virus (RSV, chicken).

48. Oncogenes and Tumor-Suppressor Genes
Proto-oncogenes
Are normal genes that can become oncogenes
Are found in many animals
Code for growth factors that stimulate cell division
For a proto-oncogene to become an oncogene, a mutation must occur in the cell’s DNA

49. Proto-oncogene DNA (a) Mutation within the gene (b) Multiple copies
of the gene
(c) Gene moved to
new DNA locus,
under new controls
Oncogene
New promoter
Normal
growth-stimulating
protein in excess
Normal
growth-stimulating
protein in excess
Hyperactive
growth-stimulating
protein
Figure 11.18

50. Tumor-suppressor genes
Help prevent uncontrolled cell growth
May be mutated, and contribute to cancer
Mutated tumor-suppressor gene
Tumor-suppressor gene
Normal
growth-
inhibiting
protein
Defective,
non-functioning
protein
Cell division
under control
Cell division not under control
Figure 11.19

51. Genes That Cause Cancer
Proto-oncogene (normal)
Genes That Cause Cancer
Oncogene
Mutation or virus
Normal protein
Mutant protein
Normal regulation of cell cycle
Out-of-control growth (leading to cancer)
Normal growth-inhibiting protein
Defective protein
Mutation or virus
Tumor-suppressor gene (normal)
Mutated tumor-suppressor gene
Visual Summary 11.6

52. The Effects of Cancer Genes on Cell-Signaling Pathways
Normal proto-oncogenes and tumor-suppressor genes
Often code for proteins involved in signal transduction
The proto-oncogene ras
Is involved in signal transduction
Can contribute to cancer if mutated

53. The Progression of a Cancer
Colon cancer begins as an unusually frequent division of normal-looking cells in the colon lining
Colon wall 1 2 3
Cellular
changes:
Increased
cell division
Growth of benign
tumor
Growth of malignant tumor
DNA
changes:
Oncogene
activated
Tumor-suppressor
gene inactivated
Second
tumor-suppressor
gene inactivated
(a) Stepwise development of a typical colon cancer
Figure 11.20a

54. Genetic changes or mutations
Result in altered signal-transduction pathways
Chromo-
somes 1
mutation 2
mutations 3
mutations 4
mutations
Normal
cell
Malignant
cell
(b) Accumulation of mutations in the development of a cancer cell
Figure 11.20b

55. “Inherited” Cancer
Cancer is always a genetic disease because it always results from changes in DNA
In some families, mutations in one or more genes predisposing the recipient to cancer can be passed on
Such a cancer is familial, or inherited

56. Breast cancer
Has nothing to do with inherited mutations in the vast majority of cases
In some families can be caused by inherited cancer genes
Can be caused by mutations affecting the BRCA1 and BRCA2 genes

57. The Effects of Lifestyle on Cancer Risk
Is one of the leading causes of death in the United States
Can be caused by carcinogens (cancer causing agent), e.g. UV radiation, Tobacco, Alcohol
Exposure to carcinogens
Is often an individual choice, but can be avoided

58. Table 11.1

59. EVOLUTION CONNECTION: HOMEOTIC GENES
effect
Homeotic genes
Are master control genes
Regulate many other genes
Help direct embryonic development in many organisms
Figure 11.21
Homeoboxes
Are sequences of nucleotides common in many organisms
Can turn groups of genes on and off during development

60. Homeotic genes in two different animals
Fly chromosome
Mouse chromosomes
Fruit fly embryo (10 hours)
Mouse embryo (12 days)
Adult fruit fly
Adult mouse
Figure 11.22