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Chapter 11

Chapter 11. 0. The Control of Gene Expression. 0. To Clone or Not to Clone? A clone is an individual created by asexual reproduction And thus is genetically identical to a single parent. 0. Cloning has many benefits But evokes just as many concerns. Colorized SEM 7,000 . Figure 11.1A.

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Chapter 11

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  1. Chapter 11 0 The Control of Gene Expression

  2. 0 • 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. 0 • Cloning has many benefits • But evokes just as many concerns

  4. Colorized SEM 7,000 Figure 11.1A GENE REGULATION 0 • 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

  5. 0 • The lac Operon • In prokaryotes, genes for related enzymes • Are often controlled together in units called operons

  6. 0 OPERON Regulatorygene Promoter Operator Lactose-utilization genes DNA mRNA RNA polymerasecannot attach topromoter Activerepressor Protein Operon turned off (lactose absent) RNA polymerasebound to promoter DNA mRNA Protein Inactiverepressor Enzymes for lactose utilization Lactose Figure 11.1B Operon turned on (lactose inactivates repressor) • Regulatory proteins bind to control sequences in the DNA • And turn operons on or off in response to environmental changes

  7. Promoter Operator Genes DNA Activerepressor Activerepressor Tryptophan Inactiverepressor Inactiverepressor Lactose Figure 11.1C lac operon trp operon 0 • Other Kinds of Operons • The trp operon • Is similar to the lac operon, but functions somewhat differently

  8. 0 • 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. Muscle cell Pancreas cells Blood cells Figure 11.2 0 • Different types of cells • Make different proteins because different combinations of genes are active in each type

  10. Root ofcarrot plant Single cell Root cells culturedin nutrient medium Cell divisionin culture Figure 11.3 Plantlet Adult Plant 0 • 11.3 Differentiated cells may retain all of their genetic potential • Most differentiated cells • Retain a complete set of genes

  11. DNA doublehelix (2-nmdiameter) Histones Linker “Beads ona string” TEM Nucleosome(10-nm diameter) Tight helical fiber(30-nm diameter) Supercoil (300-nm diameter) 700 nm TEM Figure 11.4 Metaphase chromosome 0 • 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

  12. 0 • 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. Two cell populationsin adult Early embryo Cell divisionand randomX chromosomeinactivation Orangefur Active X X chromosomes Inactive X Inactive X Black fur Allele fororange fur Active X Allele forblack fur Figure 11.5 0 • 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

  14. 0 • 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. Enhancers Promoter Gene DNA Activatorproteins Transcriptionfactors Otherproteins RNA polymerase Bendingof DNA Figure 11.6 Transcription 0 • Transcription Factors • Transcription factors • Assist in initiating eukaryotic transcription

  16. 0 • Coordinating Eukaryotic Gene Expression • Coordinated gene expression in eukaryotes • Seems to depend on the association of enhancers with groups of genes

  17. Exons DNA RNA transcript or RNA splicing Figure 11.7 mRNA 0 • 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

  18. 0 • 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. 0 • Breakdown of mRNA • The lifetime of an mRNA molecule • Helps determine how much protein is made

  20. 0 • Initiation of Translation • Among the many molecules involved in translation • Are a great many proteins that control the start of polypeptide synthesis

  21. SH Folding of polypeptide andformation of S—S linkages SH S S S Cleavage S S S SH SH S SH S SH S S S S Initial polypeptide(inactive) Folded polypeptide(inactive) Active formof insulin Figure 11.8 0 • Protein Activation • After translation is complete • Polypeptides may require alteration to become functional

  22. 0 • Protein Breakdown • Some of the proteins that trigger metabolic changes in cells • Are broken down within a few minutes or hours

  23. NUCLEUS Chromosome DNA unpacking Other changes to DNA Gene Gene Transcription Exon RNA transcript Intron Addition of cap and tail Tail Splicing mRNA in nucleus Cap Flow throughnuclear envelope mRNA in cytoplasm CYTOPLASM Breakdown of mRNA Broken-downmRNA Translation Polypeptide Cleavage / modification / activation Active protein Breakdownof protein Broken-downprotein Figure 11.9 0 • 11.9 Review: Multiple mechanisms regulate gene expression in eukaryotes

  24. Nucleus fromdonor cell Donorcell Clone of donor is born (reproductive cloning) Implant blastocyst insurrogate mother Grow in culture to produce an early embryo (blastocyst) Add somatic cell from adult donor Remove nucleusfrom egg cell Remove embryonic stemcells from blastocyst andgrow in culture Induce stem cells toform specialized cells(therapeutic cloning) Figure 11.10 ANIMAL CLONING 0 • 11.10 Nuclear transplantation can be used to clone animals

  25. Figure 11.11 CONNECTION 0 • 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

  26. 0 • Critics point out that there are many obstacles • Both practical and ethical, to human cloning

  27. Blood cells Adult stemcells in bone marrow Nerve cells Culturedembryonicstem cells Heart muscle cells Different cultureconditions Different types ofdifferentiated cells Figure 11.12 CONNECTION 0 • 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

  28. 0 • Unlike embryonic stem cells • Adult stem cells normally give rise to only a limited range of cell types

  29. Eye Antenna Leg SEM 50 Head of a developmental mutant Head of a normal fruit fly THE GENETIC CONTROL OF EMBRYONIC DEVELOPMENT 0 • 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 Figure 11.13A

  30. 0 • A cascade of gene expression • Controls the development of an animal from a fertilized egg Egg cell Egg cell within ovarianfollicle Egg proteinsignalingfollicle cells 1 Follicle cells Gene expressionin follicle cells Follicle cellproteinsignalingegg cell 2 Localization of “head” mRNA 3 “Head” mRNA Fertilization and mitosis Translation of “head” mRNA Embryo Gradient of regulatoryprotein 4 Gene expression Gradient of certainotherproteins 5 Gene expression Bodysegments 6 0.1 mm Larva Gene expression Adult fly Tail end Head end Figure 11.13B 7 0.5 mm

  31. 0 • Homeotic genes • Control batteries of genes that shape anatomical parts such as antennae

  32. 0 • 11.14 Signal transduction pathways convert messages received at the cell surface to responses within the cell

  33. 0 • Signal transduction pathways • Convert molecular messages to cell responses Signaling cell Signalmolecule 1 Plasmamembrane Receptorprotein 2 3 Target cell Relayproteins 4 Transcription factor(activated) Nucleus DNA 5 Transcription mRNA Newprotein 6 Translation Figure 11.14

  34. Fly chromosome Mouse chromosomes Fruit fly embryo (10 hours) Mouse embryo (12 days) Figure 11.15 Adult fruit fly Adult mouse 0 • 11.15 Key developmental genes are very ancient • Homeotic genes contain nucleotide sequences, called homeoboxes • That are very similar in many kinds of organisms

  35. THE GENETIC BASIS OF CANCER 0 • 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

  36. Proto-oncogene DNA Gene moved tonew DNA locus,under new controls Mutation withinthe gene Multiple copiesof the gene New promoter Oncogene Normal growth-stimulatingproteinin excess Normal growth-stimulatingproteinin excess Hyperactivegrowth-stimulatingprotein innormalamount Figure 11.16A 0 • 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

  37. Mutated tumor-suppressor gene Tumor-suppressor gene Normalgrowth-inhibitingprotein Defective,nonfunctioningprotein Cell division notunder control Cell divisionunder control Figure 11.16B 0 • Tumor-Suppressor Genes • Mutations that inactivate tumor suppressor genes • Have similar effects as oncogenes

  38. 0 • 11.17 Oncogene proteins and faulty tumor-suppressor proteins can interfere with normal signal transduction pathways

  39. 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 11.17A 0 • Oncogene proteins • Can stimulate signal transduction pathways

  40. Growth-inhibitingfactor Receptor Relayproteins Nonfunctional transcriptionfactor (product of faulty p53tumor-suppressor gene) cannot triggertranscription Transcription factor(activated) Normal product of p53 gene Transcription Translation Protein absent(cell divisionnot inhibited) Protein thatinhibitscell division Figure 11.17B 0 • Tumor-suppressor proteins • Can inhibit signal transduction pathways

  41. 0 • 11.18 Multiple genetic changes underlie the development of cancer • Cancers result from a series of genetic changes in a cell lineage

  42. 2 1 3 Increasedcell division Growth of polyp Growth of malignanttumor (carcinoma) Tumor-suppressorgene inactivated Second tumor-suppressor geneinactivated Oncogeneactivated 0 • Colon cancer • Develops in a stepwise fashion Colon wall Cellularchanges: DNAchanges: Figure 11.18A

  43. Chromosomes 1 2 4 3 mutations mutation mutations mutations Normalcell Malignantcell Figure 11.18B 0 • Accumulation of mutations • Can lead to cancer

  44. Figure 11.19 TALKING ABOUT SCIENCE 0 • 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

  45. CONNECTION 0 • 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

  46. Table 11.20 0 • Cancer in the United States

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