1. BIOLOGY CONCEPTS & CONNECTIONS Fourth Edition Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Neil A. Campbell Jane B. Reece Lawrence G. Mitchell Martha R. Taylor From PowerPoint ® Lectures for Biology: Concepts & Connections CHAPTER 11 The Control of Gene Expression Modules 11.1 – 11.11

2. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Researchers clone animals by nuclear transplantation –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

3. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings In reproductive cloning, the embryo is implanted in a surrogate mother In therapeutic cloning, the idea is to produce a source of embryonic stem cells –Stem cells can help patients with damaged tissues

4. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Remove nucleus from egg cell Donor cell Add somatic cell from adult donor Grow in culture to produce an early embryo (blastocyst) Nucleus from donor cell 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 for THERAPEUTIC use

5. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings 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 11.1 Proteins interacting with DNA turn prokaryotic genes on or off in response to environmental changes GENE REGULATION IN PROKARYOTES Figure 11.1A

6. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings 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. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings The lac operon produces enzymes that break down lactose only when lactose is present Figure 11.1B DNA mRNA Protein Regulatory gene PromoterOperatorLactose-utilization genes OPERON RNA polymerase cannot attach to promoter Active repressor OPERON TURNED OFF (lactose absent) DNA mRNA Protein OPERON TURNED ON (lactose inactivates repressor) Lactose Inactive repressor RNA polymerase bound to promoter Enzymes for lactose utilization

8. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Two types of repressor-controlled operons Figure 11.1C Tryptophan DNA PromoterOperatorGenes Active repressor Inactive repressor lac OPERONtrp OPERON Lactose

9. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings 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 11.2 Differentiation yields a variety of cell types, each expressing a different combination of genes CELLULAR DIFFERENTIATION AND THE CLONING OF EUKARYOTES

10. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Table 11.2

11. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Most differentiated cells retain a complete set of genes –In general, all somatic cells of a multicellular organism have the same genes 11.3 Differentiated cells may retain all of their genetic potential

12. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings –So a carrot plant can be grown from a single carrot cell Figure 11.3A Root of carrot plant Adult plant Root cells cultured in nutrient medium Cell division in culture Single cell Plantlet

13. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Early experiments in animal nuclear transplantation were performed on frogs –The cloning of tadpoles showed that the nuclei of differentiated animal cells retain their full genetic potential Figure 11.3B Tadpole (frog larva) Intestinal cell Frog egg cell Nucleus UV Nucleus destroyed Transplantation of nucleus Eight-cell embryo Tadpole

14. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings 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. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Scientists clone farm animals with specific sets of desirable traits Piglet clones might someday provide a source of organs for human transplant 11.4 Connection: Reproductive cloning of nonhuman mammals has applications in basic research, agriculture, and medicine Figure 11.4

16. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings 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 11.5 Connection: Because stem cells can both perpetuate themselves and give rise to differentiated cells, they have great therapeutic potential

17. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Differentiation of embryonic stem cells in culture Figure 11.5 Cultured embryonic stem cells Different culture conditions Different types of differentiated cells Heart muscle cells Nerve cells Liver cells

18. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings A chromosome contains a DNA double helix wound around clusters of histone proteins DNA packing tends to block gene expression 11.6 DNA packing in eukaryotic chromosomes helps regulate gene expression GENE REGULATION IN EUKARYOTES

19. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Figure 11.6 DNA double helix (2-nm diameter) Metaphase chromosome 700 nm Tight helical fiber (30-nm diameter) Nucleosome (10-nm diameter) Histones “Beads on a string” Supercoil (200-nm diameter)

20. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings An extreme example of DNA packing in interphase cells is X chromosome inactivation 11.7 In female mammals, one X chromosome is inactive in each cell Figure 11.7 EARLY EMBRYO Cell division and X chromosome inactivation X chromosomes Allele for orange fur Allele for black fur TWO CELL POPULATIONS IN ADULT Active X Inactive X Orange fur Inactive X Active X Black fur

21. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings A variety of regulatory proteins interact with DNA and each other –These interactions turn the transcription of eukaryotic genes on or off 11.8 Complex assemblies of proteins control eukaryotic transcription Enhancers DNA Activator proteins Other proteins Transcription factors RNA polymerase Bending of DNA Transcription Promoter Gene Figure 11.8

22. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Exons DNA RNA splicing or RNA transcript mRNA After transcription, alternative splicing may generate two or more types of mRNA from the same transcript 11.9 Eukaryotic RNA may be spliced in more than one way Figure 11.9

23. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings The lifetime of an mRNA molecule helps determine how much protein is made –The protein may need to be activated in some way 11.10 Translation and later stages of gene expression are also subject to regulation Figure 11.10 Folding of polypeptide and formation of S–S linkages Initial polypeptide (inactive) Folded polypeptide (inactive) Cleavage Active form of insulin

24. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings 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 11.11 Review: Multiple mechanisms regulate gene expression in eukaryotes

25. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Chromosome GENE RNA transcript mRNA in nucleus mRNA in cytoplasm Polypeptide ACTIVE PROTEIN GENE Exon Intron Tail Cap NUCLEUS Flow through nuclear envelope CYTOPLASM Breakdown of mRNA TranslationBroken- down mRNA Broken- down protein Cleavage/modification/ activation Breakdown of protein DNA unpacking Other changes to DNA TRANSCRIPTION Addition of cap and tail Splicing Figure 11.11

26. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings A mutation can change a proto-oncogene into an oncogene –An oncogene causes cells to divide excessively 11.15 Cancer results from mutations in genes that control cell division THE GENETIC BASIS OF CANCER Mutation within the gene Oncogene Multiple copies of the gene Hyperactive growth-stimulating protein in normal amount Normal growth- stimulating protein in excess Gene moved to new DNA locus, under new controls New promoter Normal growth- stimulating protein in excess Proto-oncogene DNA Figure 11.15A

27. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Mutations that inactivate tumor-suppressor genes have similar effects Figure 11.15B Normal growth- inhibiting protein Cell division under control Tumor-suppressor gene Defective, nonfunctioning protein Cell division not under control Mutated tumor-suppressor gene

28. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings 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. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Figure 11.16A Normal product of ras gene TARGET CELL GROWTH FACTOR Receptor Hyperactive relay protein (product of ras oncogene) issues signals on its own Relay proteins Transcription factor (activated) DNA NUCLEUS Transcription Translation Protein that STIMULATES cell division

30. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Other cancer- causing mutations inhibit the cell’s ability to repair damaged DNA Figure 11.16B GROWTH- INHIBITING FACTOR Receptor Nonfunctional transcription factor (product of faulty p53 tumor-suppressor gene) cannot trigger transcription Relay proteins Transcription factor (activated) Transcription Translation Protein that INHIBITS cell division Normal product of p53 gene Protein absent (cell division not inhibited)

31. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings 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 Figure 11.17A CELLULAR CHANGES: Colon wall 1 DNA CHANGES: 23 Increased cell division Oncogene activated Growth of polyp Tumor-suppressor gene inactivated Growth of malignant tumor (carcinoma) Second tumor-suppressor gene inactivated

32. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Mutations that lead to cancer may accumulate in a lineage of somatic cells Figure 11.17B Chromosomes 1 mutation 2 mutations 3 mutations 4 mutations Normal cell Malignant cell

33. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings 11.18 Talking about Science: Mary-Claire King discusses mutations that cause breast cancer Figure 11.18 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

34. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings 11.19 Connection: Avoiding carcinogens can reduce the risk of cancer Table 11.19 Lifestyle choices can help reduce cancer risk

35. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings A cascade of gene expression involves genes for regulatory proteins that affect other genes –It determines how an animal develops from a fertilized egg 11.12 Cascades of gene expression and cell-to-cell signaling direct the development of an animal

36. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Mutant fruit flies show the relationship between gene expression and development –Some mutants have legs where antennae should be Figure 11.12A Eye Antenna Head of a normal fruit fly Head of a developmental mutant Leg

37. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Development of head-tail polarity in fruit fly Figure 11.12B EGG CELL WITHIN OVARIAN FOLLICLE 1 Egg cell Egg protein signaling follicle cells Gene expression in follicle cells Follicle cell protein signaling egg cell Localization of “head” mRNA 2 3 “Head” mRNA Follicle cells

38. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings EMBRYO 4 Gradient of regulatory protein Gene expression Translation of “head” mRNA Gradient of certain other proteins Gene expression Body segments 5 6 FERTILIZATION AND MITOSIS ZYGOTE Figure 11.12B

39. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Body segments Gene expressionLARVA ADULT FLY Head end 6 7 Tail end EMBRYO Figure 11.12B

40. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Cell-to-cell signaling is important in –development –coordination of cellular activities 11.13 Signal-transduction pathways convert messages received at the cell surface into responses within the cell

41. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings A signal-transduction pathway that turns on a gene (1) The signaling cell secretes the signal molecule (2) The signal molecule binds to a receptor protein in the target cell’s plasma membrane SIGNALING CELL 1 Signal molecule Receptor protein Plasma membrane 2 Figure 11.13 TARGET CELL

42. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings (3) Binding activates the first relay protein, which then activates the next relay protein, etc. (4) The last relay protein activates a transcription factor SIGNALING CELL 1 Signal molecule Receptor protein Plasma membrane 2 3 TARGET CELL Relay proteins 4 Transcription factor (activated) Figure 11.13

43. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings SIGNALING CELL 1 Signal molecule Receptor protein Plasma membrane 2 3 TARGET CELL Relay proteins 4 Transcription factor (activated) 5 NUCLEUS DNA mRNA Transcription 6 Translation New protein (5)The transcription factor triggers transcription of a specific gene (6)Translation of the mRNA produces a protein Figure 11.13

44. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Homeotic genes –contain nucleotide sequences called homeoboxes –are similar in many kinds of organisms –arose early in the history of life 11.14 Key developmental genes are very ancient

45. Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Fruit flies and mice have similar homeotic genes (colored boxes) The order of homeotic genes is the same The gene order corresponds to analogous body regions Figure 11.14 Mouse chromosomes Mouse embryo (12 days) Adult mouse Fly chromosomes Fruit fly embryo (10 hours) Adult fruit fly