1. Copyright © 2005 Pearson Education, Inc. Publishing as Benjamin Cummings PowerPoint Lectures for Biology: Concepts and Connections, Fifth Edition – Campbell, Reece, Taylor, and Simon Lectures by Chris Romero Chapter 11 The Control of Gene Expression

2. Copyright © 2005 Pearson Education, Inc. Publishing as Benjamin Cummings To Clone or Not to Clone? A clone is an individual created by asexual reproduction –And thus is genetically identical to a single parent

3. Copyright © 2005 Pearson Education, Inc. Publishing as Benjamin Cummings Cloning has many benefits –But evokes just as many concerns

4. Copyright © 2005 Pearson Education, Inc. Publishing as Benjamin Cummings 11.1 Proteins interacting with DNA turn prokaryotic genes on or off in response to environmental changes Early understanding of gene control –Came from studies of the bacterium Escherichia coli GENE REGULATION Figure 11.1A Colorized SEM 7,000 

5. Copyright © 2005 Pearson Education, Inc. Publishing as Benjamin Cummings The lac Operon In prokaryotes, genes for related enzymes –Are often controlled together in units called operons

6. Copyright © 2005 Pearson Education, Inc. Publishing as Benjamin Cummings Regulatory proteins bind to control sequences in the DNA –And turn operons on or off in response to environmental changes DNA mRNA DNA Protein mRNA Protein Lactose Promoter Operator Lactose-utilization genes Active repressor RNA polymerase cannot attach to promoter RNA polymerase bound to promoter Inactive repressor Enzymes for lactose utilization OPERON Operon turned off (lactose absent) Operon turned on (lactose inactivates repressor) Regulatory gene Figure 11.1B

7. Copyright © 2005 Pearson Education, Inc. Publishing as Benjamin Cummings Other Kinds of Operons The trp operon –Is similar to the lac operon, but functions somewhat differently Promoter DNA Active repressor Inactive repressor Lactose Active repressor Tryptophan Inactive repressor lac operon trp operon Operator Genes Figure 11.1C

8. Copyright © 2005 Pearson Education, Inc. Publishing as Benjamin Cummings 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

9. Copyright © 2005 Pearson Education, Inc. Publishing as Benjamin Cummings Different types of cells –Make different proteins because different combinations of genes are active in each type Muscle cellPancreas cellsBlood cells Figure 11.2

10. Copyright © 2005 Pearson Education, Inc. Publishing as Benjamin Cummings 11.3 Differentiated cells may retain all of their genetic potential Most differentiated cells –Retain a complete set of genes Root of carrot plant Root cells cultured in nutrient medium Cell division in culture Plantlet Adult Plant Single cell Figure 11.3

11. Copyright © 2005 Pearson Education, Inc. Publishing as Benjamin Cummings 11.4 DNA packing in eukaryotic chromosomes helps regulate gene expression A chromosome contains DNA –Wound around clusters of histone proteins, forming a string of beadlike nucleosomes DNA double helix (2-nm diameter) Histones Linker “Beads on a string” Nucleosome (10-nm diameter) Tight helical fiber (30-nm diameter) Supercoil (300-nm diameter) Metaphase chromosome 700 nm TEM Figure 11.4

12. Copyright © 2005 Pearson Education, Inc. Publishing as Benjamin Cummings This beaded fiber –Is further wound and folded DNA packing tends to block gene expression –Presumably by preventing access of transcription proteins to the DNA

13. Copyright © 2005 Pearson Education, Inc. Publishing as Benjamin Cummings 11.5 In female mammals, one X chromosome is inactive in each cell An extreme example of DNA packing in interphase cells –Is X chromosome inactivation in the cells of female mammals Early embryo X chromosomes Allele for orange fur Allele for black fur Cell division and random X chromosome inactivation Two cell populations in adult Active X Inactive X Active X Orange fur Black fur Figure 11.5

14. Copyright © 2005 Pearson Education, Inc. Publishing as Benjamin Cummings 11.6 Complex assemblies of proteins control eukaryotic transcription A variety of regulatory proteins interact with DNA and with each other –To turn the transcription of eukaryotic genes on or off

15. Copyright © 2005 Pearson Education, Inc. Publishing as Benjamin Cummings Transcription Factors Transcription factors –Assist in initiating eukaryotic transcription Enhancers Promoter Gene DNA Activator proteins Other proteins Transcription factors RNA polymerase Bending of DNA Transcription Figure 11.6

16. Copyright © 2005 Pearson Education, Inc. Publishing as Benjamin Cummings Coordinating Eukaryotic Gene Expression Coordinated gene expression in eukaryotes –Seems to depend on the association of enhancers with groups of genes

17. Copyright © 2005 Pearson Education, Inc. Publishing as Benjamin Cummings 11.7 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 DNA RNA transcript mRNA Exons or RNA splicing Figure 11.7

18. Copyright © 2005 Pearson Education, Inc. Publishing as Benjamin Cummings 11.8 Translation and later stages of gene expression are also subject to regulation After eukaryotic mRNA is fully processed and transported to the cytoplasm –There are additional opportunities for regulation

19. Copyright © 2005 Pearson Education, Inc. Publishing as Benjamin Cummings Breakdown of mRNA The lifetime of an mRNA molecule –Helps determine how much protein is made

20. Copyright © 2005 Pearson Education, Inc. Publishing as Benjamin Cummings Initiation of Translation Among the many molecules involved in translation –Are a great many proteins that control the start of polypeptide synthesis

21. Copyright © 2005 Pearson Education, Inc. Publishing as Benjamin Cummings Protein Activation After translation is complete –Polypeptides may require alteration to become functional Folding of polypeptide and formation of S—S linkages Cleavage SH S S S S S S S S S S S S Initial polypeptide (inactive) Folded polypeptide (inactive) Active form of insulin SH Figure 11.8

22. Copyright © 2005 Pearson Education, Inc. Publishing as Benjamin Cummings Protein Breakdown Some of the proteins that trigger metabolic changes in cells –Are broken down within a few minutes or hours

23. Copyright © 2005 Pearson Education, Inc. Publishing as Benjamin Cummings 11.9 Review: Multiple mechanisms regulate gene expression in eukaryotes N UCLEUS Chromosome Gene RNA transcript mRNA in nucleus mRNA in cytoplasm Polypeptide Active protein Breakdown of protein Cleavage / modification / activation Translation Breakdown of mRNA CYTOPLASM Flow through nuclear envelope Splicing Addition of cap and tail Transcription DNA unpacking Other changes to DNA Gene Exon Intron Cap Tail Broken- down mRNA Broken- down protein Figure 11.9

24. Copyright © 2005 Pearson Education, Inc. Publishing as Benjamin Cummings 11.10 Nuclear transplantation can be used to clone animals ANIMAL CLONING 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 Induce stem cells to form specialized cells (therapeutic cloning) Clone of donor is born (reproductive cloning) Donor cell Nucleus from donor cell Figure 11.10

25. Copyright © 2005 Pearson Education, Inc. Publishing as Benjamin Cummings 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 CONNECTION Figure 11.11

26. Copyright © 2005 Pearson Education, Inc. Publishing as Benjamin Cummings Critics point out that there are many obstacles –Both practical and ethical, to human cloning

27. Copyright © 2005 Pearson Education, Inc. Publishing as Benjamin Cummings 11.12 Therapeutic cloning can produce stem cells with great medical potential Like embryonic stem cells, adult stem cells –Can perpetuate themselves in culture and give rise to differentiated cells CONNECTION Adult stem cells in bone marrow Cultured embryonic stem cells Different culture conditions Heart muscle cells Different types of differentiated cells Nerve cells Blood cells Figure 11.12

28. Copyright © 2005 Pearson Education, Inc. Publishing as Benjamin Cummings Unlike embryonic stem cells –Adult stem cells normally give rise to only a limited range of cell types

29. Copyright © 2005 Pearson Education, Inc. Publishing as Benjamin Cummings 11.13 Cascades of gene expression and cell-to-cell signaling direct the development of an animal Early understanding of the relationship between gene expression and embryonic development –Came from studies of mutants of the fruit fly Drosophila melanogaster THE GENETIC CONTROL OF EMBRYONIC DEVELOPMENT Eye Antenna Leg SEM 50  Head of a normal fruit fly Head of a developmental mutant Figure 11.13A

30. Copyright © 2005 Pearson Education, Inc. Publishing as Benjamin Cummings A cascade of gene expression –Controls the development of an animal from a fertilized egg Egg cell within ovarian follicle 1 2 Follicle cells Egg cell Egg protein signaling follicle cells Gene expression in follicle cells Follicle cell protein signaling egg cell Localization of “head” mRNA 3 Fertilization and mitosis Translation of “head” mRNA Gradient of regulatory protein Gene expression Gradient of certain other proteins Gene expression Body segments 0.1 mm Tail end 0.5 mm Head end 4 5 6 7 Adult fly Embryo “Head” mRNA Larva Figure 11.13B

31. Copyright © 2005 Pearson Education, Inc. Publishing as Benjamin Cummings Homeotic genes –Control batteries of genes that shape anatomical parts such as antennae

32. Copyright © 2005 Pearson Education, Inc. Publishing as Benjamin Cummings 11.14 Signal transduction pathways convert messages received at the cell surface to responses within the cell

33. Copyright © 2005 Pearson Education, Inc. Publishing as Benjamin Cummings Signal transduction pathways –Convert molecular messages to cell responses Signaling cell Signal molecule Receptor protein Plasma membrane Target cell Relay proteins Transcription factor (activated) Transcription Nucleus DNA mRNA New protein Translation 1 2 3 4 5 6 Figure 11.14

34. Copyright © 2005 Pearson Education, Inc. Publishing as Benjamin Cummings 11.15 Key developmental genes are very ancient Homeotic genes contain nucleotide sequences, called homeoboxes –That are very similar in many kinds of organisms Fly chromosome Mouse chromosomes Fruit fly embryo (10 hours) Mouse embryo (12 days) Adult fruit fly Adult mouse Figure 11.15

35. Copyright © 2005 Pearson Education, Inc. Publishing as Benjamin Cummings 11.15 Cancer results from mutations in genes that control cell division Cancer cells, which divide uncontrollably –Result from mutations in genes whose protein products affect the cell cycle THE GENETIC BASIS OF CANCER

36. Copyright © 2005 Pearson Education, Inc. Publishing as Benjamin Cummings Proto-Oncogenes A mutation can change a proto-oncogene (a normal gene that promotes cell division) –Into an oncogene, which causes cells to divide excessively 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 Figure 11.16A

37. Copyright © 2005 Pearson Education, Inc. Publishing as Benjamin Cummings Tumor-Suppressor Genes Mutations that inactivate tumor suppressor genes –Have similar effects as oncogenes Tumor-suppressor gene Mutated tumor-suppressor gene Normal growth- inhibiting protein Cell division under control Defective, nonfunctioning protein Cell division not under control Figure 11.16B

38. Copyright © 2005 Pearson Education, Inc. Publishing as Benjamin Cummings 11.17 Oncogene proteins and faulty tumor- suppressor proteins can interfere with normal signal transduction pathways

39. Copyright © 2005 Pearson Education, Inc. Publishing as Benjamin Cummings Oncogene proteins –Can stimulate signal transduction pathways Growth factor Target cell Receptor 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 Figure 11.17A

40. Copyright © 2005 Pearson Education, Inc. Publishing as Benjamin Cummings Tumor-suppressor proteins –Can inhibit signal transduction pathways Growth-inhibiting factor Receptor Nonfunctional transcription factor (product of faulty p53 tumor-suppressor gene) Relay proteins Transcription factor (activated) Transcription Translation Protein that inhibits cell division cannot trigger transcription Protein absent (cell division not inhibited) Normal product of p53 gene Figure 11.17B

41. Copyright © 2005 Pearson Education, Inc. Publishing as Benjamin Cummings 11.18 Multiple genetic changes underlie the development of cancer Cancers result from a series of genetic changes in a cell lineage

42. Copyright © 2005 Pearson Education, Inc. Publishing as Benjamin Cummings Colon cancer –Develops in a stepwise fashion Colon wall Cellular changes: DNA changes: 1 Increased cell division Oncogene activated 2 Growth of polyp Tumor-suppressor gene inactivated 3 Growth of malignant tumor (carcinoma) Second tumor- suppressor gene inactivated Figure 11.18A

43. Copyright © 2005 Pearson Education, Inc. Publishing as Benjamin Cummings Accumulation of mutations –Can lead to cancer Chromosomes mutation 1 2 3 4 mutations Normal cell Malignant cell Figure 11.18B

44. Copyright © 2005 Pearson Education, Inc. Publishing as Benjamin Cummings 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 in which a disease- predisposing mutation is inherited TALKING ABOUT SCIENCE Figure 11.19

45. Copyright © 2005 Pearson Education, Inc. Publishing as Benjamin Cummings 11.20 Avoiding carcinogens can reduce the risk of cancer Reducing exposure to carcinogens (which induce cancer-causing mutations) –And making other lifestyle choices can help reduce cancer risk CONNECTION

46. Copyright © 2005 Pearson Education, Inc. Publishing as Benjamin Cummings Cancer in the United States Table 11.20