CHAPTER 11 The Control of Gene Expression

1. CHAPTER 11The Control of Gene Expression Modules 11.1 – 11.11

2. A nucleus of an egg cell is replaced with the nucleus of a somatic cell from an adult • Thus far, attempts at human cloning have not succeeded in producing an embryo of more than 6 cells • Embryonic development depends on the control of gene expression • Researchers clone animals by nuclear transplantation

3. In therapeutic cloning, the idea is to produce a source of embryonic stem cells • Stem cells can help patients with damaged tissues • In reproductive cloning, the embryo is implanted in a surrogate mother

4. Donorcell Nucleus fromdonor cell Implant blastocystin surrogate mother Clone of donoris born(REPRODUCTIVEcloning) Removenucleusfrom eggcell Add somaticcell fromadult donor Grow in culture to producean early embryo (blastocyst) Remove embryonic stem cells from blastocyst andgrow in culture Induce stemcells to formspecialized cellsfor THERAPEUTICuse

5. GENE REGULATION IN PROKARYOTES 11.1 Proteins interacting with DNA turn prokaryotic genes on or off in response to environmental changes • The process by which genetic information flows from genes to proteins is called gene expression • Our earliest understanding of gene control came from the bacterium E. coli Figure 11.1A

6. In prokaryotes, genes for related enzymes are often controlled together by being grouped into regulatory units called operons • Regulatory proteins bind to control sequences in the DNA and turn operons on or off in response to environmental changes

7. OPERON Regulatorygene Promoter Operator Lactose-utilization genes • The lac operon produces enzymes that break down lactose only when lactose is present DNA mRNA RNA polymerasecannot attach topromoter Activerepressor Protein OPERON TURNED OFF (lactose absent) DNA RNA polymerasebound to promoter mRNA Protein Inactiverepressor Lactose Enzymes for lactose utilization Figure 11.1B OPERON TURNED ON (lactose inactivates repressor)

8. Two types of repressor-controlled operons Promoter Operator Genes DNA Activerepressor Activerepressor Tryptophan Inactiverepressor Inactiverepressor Lactose lac OPERON trp OPERON Figure 11.1C

9. CELLULAR DIFFERENTIATION AND THE CLONING OF EUKARYOTES 11.2 Differentiation yields a variety of cell types, each expressing a different combination of genes • In multicellular eukaryotes, cells become specialized as a zygote develops into a mature organism • Different types of cells make different kinds of proteins • Different combinations of genes are active in each type

10. Table 11.2

11. 11.3 Differentiated cells may retain all of their genetic potential • Most differentiated cells retain a complete set of genes • In general, all somatic cells of a multicellular organism have the same genes

12. So a carrot plant can be grown from a single carrot cell Root ofcarrot plant Plantlet Cell divisionin culture Single cell Adult plant Root cells cultured in nutrient medium Figure 11.3A

13. The cloning of tadpoles showed that the nuclei of differentiated animal cells retain their full genetic potential • Early experiments in animal nuclear transplantation were performed on frogs Tadpole (frog larva) Frog egg cell Nucleus UV Intestinal cell Nucleus Transplantationof nucleus Nucleusdestroyed Tadpole Eight-cellembryo Figure 11.3B

14. The first mammalian clone, a sheep named Dolly, was produced in 1997 • Dolly provided further evidence for the developmental potential of cell nuclei Figure 11.3C

15. 11.4 Connection: Reproductive cloning of nonhuman mammals has applications in basic research, agriculture, and medicine • Scientists clone farm animals with specific sets of desirable traits • Piglet clones might someday provide a source of organs for human transplant Figure 11.4

16. 11.5 Connection: Because stem cells can both perpetuate themselves and give rise to differentiated cells, they have great therapeutic potential • Adult stem cells can also perpetuate themselves in culture and give rise to differentiated cells • But they are harder to culture than embryonic stem cells • They generally give rise to only a limited range of cell types, in contrast with embryonic stem cells

17. Differentiation of embryonic stem cells in culture Liver cells Culturedembryonicstem cells Nerve cells Heart muscle cells Different cultureconditions Different types ofdifferentiated cells Figure 11.5

18. GENE REGULATION IN EUKARYOTES 11.6 DNA packing in eukaryotic chromosomes helps regulate gene expression • A chromosome contains a DNA double helix wound around clusters of histone proteins • DNA packing tends to block gene expression

19. DNAdoublehelix(2-nmdiameter) Histones “Beads ona string” Nucleosome(10-nm diameter) Tight helical fiber(30-nm diameter) Supercoil(200-nm diameter) 700nm Metaphase chromosome Figure 11.6

20. 11.7 In female mammals, one X chromosome is inactive in each cell • An extreme example of DNA packing in interphase cells is X chromosome inactivation EARLY EMBRYO TWO CELL POPULATIONSIN ADULT Cell divisionandX chromosomeinactivation Orange fur Active X X chromosomes Inactive X Inactive X Allele fororange fur Black fur Active X Allele forblack fur Figure 11.7

21. 11.8 Complex assemblies of proteins control eukaryotic transcription • A variety of regulatory proteins interact with DNA and each other • These interactions turn the transcription of eukaryotic genes on or off Enhancers Promoter Gene DNA Activatorproteins Transcriptionfactors Otherproteins RNA polymerase Bendingof DNA Figure 11.8 Transcription

22. 11.9 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 Exons DNA RNAtranscript RNA splicing or mRNA Figure 11.9

23. 11.10 Translation and later stages of gene expression are also subject to regulation • The lifetime of an mRNA molecule helps determine how much protein is made • The protein may need to be activated in some way Folding of polypeptide andformation of S–S linkages Cleavage Initial polypeptide(inactive) Folded polypeptide(inactive) Active formof insulin Figure 11.10

24. 11.11 Review: Multiple mechanisms regulate gene expression in eukaryotes • Each stage of eukaryotic expression offers an opportunity for regulation • The process can be turned on or off, speeded up, or slowed down • The most important control point is usually the start of transcription

25. Chromosome DNA unpackingOther changes to DNA GENE TRANSCRIPTION GENE Exon RNA transcript Intron Addition of cap and tail Splicing Tail Cap mRNA in nucleus NUCLEUS Flowthroughnuclear envelope mRNA in cytoplasm CYTOPLASM Breakdown of mRNA Translation Broken-down mRNA Polypeptide Cleavage/modification/activation ACTIVE PROTEIN Breakdownof protein Broken-down protein Figure 11.11

26. THE GENETIC BASIS OF CANCER 11.15 Cancer results from mutations in genes that control cell division • A mutation can change a proto-oncogene into an oncogene • An oncogene causes cells to divide excessively Proto-oncogene DNA Mutation within the gene Multiple copies of the gene Gene moved tonew DNA locus,under new controls Oncogene New promoter Hyperactivegrowth-stimulatingprotein in normalamount Normal growth-stimulatingproteinin excess Normal growth-stimulatingproteinin excess Figure 11.15A

27. Tumor-suppressor gene Mutated tumor-suppressor gene • Mutations that inactivate tumor-suppressor genes have similar effects Normalgrowth-inhibitingprotein Defective,nonfunctioningprotein Cell divisionunder control Cell division notunder control Figure 11.15B

28. 11.16 Oncogene proteins and faulty tumor-suppressor proteins can interfere with normal signal-transduction pathways • Mutations of these genes cause malfunction of the pathway

29. GROWTHFACTOR Receptor TARGET CELL Hyperactiverelay protein(product ofras oncogene)issues signalson its own Normal productof ras gene Relayproteins Transcription factor(activated) DNA NUCLEUS Transcription Translation Protein thatSTIMULATEScell division Figure 11.16A

30. GROWTH-INHIBITINGFACTOR Receptor • Other cancer-causing mutations inhibit the cell’s ability to repair damaged DNA Relayproteins Nonfunctional transcriptionfactor (product of faulty p53tumor-suppressor gene) cannot trigger transcription Transcription factor(activated) Normal productof p53 gene Transcription Translation Protein thatINHIBITScell division Protein absent(cell divisionnot inhibited) Figure 11.16B

31. 11.17 Multiple genetic changes underlie the development of cancer • Cancers result from a series of genetic changes in a cell lineage • As in many cancers, the development of colon cancer is gradual Colon wall 1 2 3 CELLULARCHANGES: Increasedcell division Growth of polyp Growth of malignanttumor (carcinoma) DNACHANGES: Oncogeneactivated Tumor-suppressorgene inactivated Second tumor-suppressorgene inactivated Figure 11.17A

32. Mutations that lead to cancer may accumulate in a lineage of somatic cells Chromosomes 1mutation 2mutations 3mutations 4mutations Normalcell Malignantcell Figure 11.17B

33. 11.18 Talking about Science: Mary-Claire King discusses mutations that cause breast cancer • Researchers have gained insight into the genetic basis of breast cancer • Studies have been done of families in which a disease-predisposing mutation is inherited Figure 11.18

34. 11.19 Connection: Avoiding carcinogens can reduce the risk of cancer • Lifestyle choices can help reduce cancer risk Table 11.19

35. 11.12 Cascades of gene expression and cell-to-cell signaling direct the development of an animal • A cascade of gene expression involves genes for regulatory proteins that affect other genes • It determines how an animal develops from a fertilized egg

36. Eye • Mutant fruit flies show the relationship between gene expression and development Antenna • Some mutants have legs where antennae should be Head of a normal fruit fly Leg Head of a developmental mutant Figure 11.12A

37. EGG CELL WITHIN OVARIAN FOLLICLE Egg cell Egg protein signaling follicle cells 1 • Development of head-tail polarity in fruit fly Follicle cells Gene expression in follicle cells Follicle cell protein signaling egg cell 2 Localization of “head” mRNA 3 “Head” mRNA Figure 11.12B

38. FERTILIZATION AND MITOSIS ZYGOTE Translation of “head” mRNA EMBRYO Gradient of regulatory protein 4 Gene expression Gradient of certain other proteins 5 Gene expression Body segments 6 Figure 11.12B

39. EMBRYO Body segments 6 LARVA Gene expression ADULT FLY 7 Head end Tail end Figure 11.12B

40. 11.13 Signal-transduction pathways convert messages received at the cell surface into responses within the cell • Cell-to-cell signaling is important in • development • coordination of cellular activities

41. SIGNALING CELL Signal molecule 1 Plasma membrane Receptor protein 2 • A signal-transduction pathway that turns on a gene (1) The signaling cell secretes the signal molecule TARGET CELL (2) The signal molecule binds to a receptor protein in the target cell’s plasma membrane Figure 11.13

42. SIGNALING CELL Signal molecule 1 Plasma membrane Receptor protein 2 (3) Binding activates the first relay protein, which then activates the next relay protein, etc. 3 TARGET CELL Relay proteins 4 Transcription factor (activated) (4) The last relay protein activates a transcription factor Figure 11.13

43. SIGNALING CELL Signal molecule 1 Plasma membrane Receptor protein 2 (5) The transcription factor triggers transcription of a specific gene 3 TARGET CELL Relay proteins 4 Transcription factor (activated) (6) Translation of the mRNA produces a protein NUCLEUS DNA 5 Transcription mRNA New protein 6 Translation Figure 11.13

44. 11.14 Key developmental genes are very ancient • Homeotic genes • contain nucleotide sequences called homeoboxes • are similar in many kinds of organisms • arose early in the history of life

45. The order of homeotic genes is the same • The gene ordercorresponds toanalogous bodyregions Fly chromosomes Mouse chromosomes • Fruit flies and mice have similar homeotic genes (colored boxes) Fruit fly embryo (10 hours) Mouse embryo (12 days) Adult fruit fly Adult mouse Figure 11.14