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BIOLOGY CONCEPTS & CONNECTIONS Fourth Edition Neil A. Campbell • Jane B. Reece • Lawrence G. Mitchell • Martha R. Taylor CHAPTER 11 The Control of Gene Expression Modules 11.1 – 11.11 From PowerPoint® Lectures for Biology: Concepts & Connections 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 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 Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Donor cell Nucleus from donor cell Remove nucleus from egg cell Add somatic cell from adult donor Implant blastocyst in surrogate mother Clone of donor is born (REPRODUCTIVE cloning) Remove embryonic stem cells from blastocyst and grow in culture Induce stem cells to form specialized cells for THERAPEUTIC use Grow in culture to produce an early embryo (blastocyst) Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings 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 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 Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings • The lac operon produces enzymes that break down lactose only when lactose is present OPERON Regulatory gene Promoter Operator Lactose-utilization genes DNA mRNA RNA polymerase cannot attach to promoter Active repressor Protein OPERON TURNED OFF (lactose absent) DNA RNA polymerase bound to promoter mRNA Protein Lactose Inactive repressor Enzymes for lactose utilization OPERON TURNED ON (lactose inactivates repressor) Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Figure 11.1B • Two types of repressor-controlled operons Promoter Operator Genes DNA Active repressor Active repressor Tryptophan Inactive repressor Inactive repressor Lactose lac OPERON Figure 11.1C Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings trp OPERON 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 Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Table 11.2 Copyright © 2003 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 – In general, all somatic cells of a multicellular organism have the same genes Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings – So a carrot plant can be grown from a single carrot cell Root of carrot plant Plantlet Cell division in culture Single cell Root cells cultured in nutrient medium Figure 11.3A Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Adult plant • 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 Tadpole (frog larva) Frog egg cell Nucleus UV Intestinal cell Nucleus Transplantation of nucleus Nucleus destroyed Tadpole Eight-cell embryo Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Figure 11.3B • 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 Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings 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 Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings 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 Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings • Differentiation of embryonic stem cells in culture Liver cells Cultured embryonic stem cells Nerve cells Heart muscle cells Figure 11.5 Different culture conditions Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Different types of differentiated cells 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 Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings DNA double helix (2-nm diameter) Histones “Beads on a string” Nucleosome (10-nm diameter) Tight helical fiber (30-nm diameter) Supercoil (200-nm diameter) 700 nm Figure 11.6 Metaphase chromosome Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings 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 POPULATIONS IN ADULT Cell division and X chromosome inactivation X chromosomes Allele for orange fur Active X Inactive X Inactive X Active X Orange fur Black fur Allele for black fur Figure 11.7 Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings 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 Transcription factors Activator proteins Other proteins RNA polymerase Bending of DNA Figure 11.8 Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Transcription 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 RNA transcript RNA splicing mRNA Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings or Figure 11.9 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 and formation of S–S linkages Initial polypeptide (inactive) Folded polypeptide (inactive) Cleavage Active form of insulin Figure 11.10 Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings 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 Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Chromosome DNA unpacking Other changes to DNA GENE GENE TRANSCRIPTION Exon RNA transcript Intron Addition of cap and tail Splicing Tail Cap mRNA in nucleus NUCLEUS Flow through nuclear envelope mRNA in cytoplasm CYTOPLASM Breakdown of mRNA Translation Brokendown mRNA Polypeptide Cleavage/modification/ activation ACTIVE PROTEIN Breakdown of protein Brokendown protein Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Figure 11.11 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 Mutation within the gene DNA Multiple copies of the gene Oncogene Hyperactive growth-stimulating protein in normal amount Gene moved to new DNA locus, under new controls New promoter Normal growthstimulating protein in excess Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Normal growthstimulating protein in excess Figure 11.15A • Mutations that inactivate tumor-suppressor genes have similar effects Tumor-suppressor gene Mutated tumor-suppressor gene Normal growthinhibiting protein Defective, nonfunctioning protein Cell division under control Cell division not under control Figure 11.15B Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings 11.16 Oncogene proteins and faulty tumorsuppressor proteins can interfere with normal signal-transduction pathways • Mutations of these genes cause malfunction of the pathway Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings GROWTH FACTOR Receptor TARGET CELL 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 Protein that STIMULATES cell division Translation Figure 11.16A Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings • Other cancercausing mutations inhibit the cell’s ability to repair damaged DNA GROWTHINHIBITING FACTOR Relay proteins Transcription factor (activated) Receptor Nonfunctional transcription factor (product of faulty p53 tumor-suppressor gene) cannot trigger transcription Normal product of p53 gene Transcription Translation Figure 11.16B Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Protein that INHIBITS cell division Protein absent (cell division not inhibited) 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 Figure 11.17A 2 3 CELLULAR CHANGES: Increased cell division Growth of polyp Growth of malignant tumor (carcinoma) DNA CHANGES: Oncogene activated Tumor-suppressor gene inactivated Second tumor-suppressor gene inactivated Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings • Mutations that lead to cancer may accumulate in a lineage of somatic cells Chromosomes 1 mutation 2 mutations Normal cell 3 mutations 4 mutations Malignant cell Figure 11.17B Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings 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 Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings 11.19 Connection: Avoiding carcinogens can reduce the risk of cancer • Lifestyle choices can help reduce cancer risk Table 11.19 Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings 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 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 Eye Antenna Head of a normal fruit fly Leg Figure 11.12A Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Head of a developmental mutant • Development of head-tail polarity in fruit fly EGG CELL WITHIN OVARIAN FOLLICLE Egg cell Egg protein signaling follicle cells 1 Follicle cells 2 Gene expression in follicle cells Follicle cell protein signaling egg cell Localization of “head” mRNA 3 “Head” mRNA Figure 11.12B Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings ZYGOTE FERTILIZATION AND MITOSIS EMBRYO Translation of “head” mRNA Gradient of regulatory protein 4 Gene expression 5 Gradient of certain other proteins Gene expression Body segments 6 Figure 11.12B Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings EMBRYO Body segments 6 LARVA Gene expression ADULT FLY 7 Head end Tail end Figure 11.12B Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings 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 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 SIGNALING CELL 1 2 TARGET CELL (2) The signal molecule binds to a receptor protein in the target cell’s plasma membrane Figure 11.13 Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Signal molecule Receptor protein Plasma membrane SIGNALING CELL Signal molecule 1 (3) Binding activates the first relay protein, which then activates the next relay protein, etc. (4) The last relay protein activates a transcription factor Figure 11.13 Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Receptor protein 2 Plasma membrane 3 TARGET CELL Relay proteins Transcription factor (activated) 4 SIGNALING CELL Signal molecule 1 Receptor protein 2 (5) The transcription factor triggers transcription of a specific gene Plasma membrane 3 TARGET CELL Relay proteins Transcription factor (activated) (6) Translation of the mRNA produces a protein 4 NUCLEUS DNA 5 Transcription mRNA New protein 6 Figure 11.13 Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Translation 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 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 Fly chromosomes Mouse chromosomes Fruit fly embryo (10 hours) Mouse embryo (12 days) Adult fruit fly Adult mouse Figure 11.14 Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings