Controls Over Genes. Chapter 15
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1 Controls Over Genes Chapter 15
2 Impacts, Issues: Between You and Eternity Mutations in some genes predispose individuals to develop certain kinds of cancer; mutations in BRAC genes cause breast cancer
3 normal cells in organized clusters irregular clusters of malignant cells Fig. 15-1b, p. 228
4 15.1 Gene Expression in Eukaryotic Cells Gene controls govern the kinds and amounts of substances in a cell at any given interval Various control processes regulate all steps between gene and gene product
5 Which Genes Get Tapped? Differentiation The process by which cells become specialized In multicelled organisms, most cells differentiate when they start expressing a unique subset of their genes Which genes are expressed depends on the type of organism, its stage of development, and environmental conditions
6 Control of Transcription Transcription factors Regulatory proteins that affect the rate of transcription by binding to special nucleotide sequences in DNA Activators speed up transcription when bound to a promoter; or may bind to distant enhancers Repressors slow or stop transcription
7 Promoter and Enhancers
8 enhancer promoter exon1 intron exon2 enhancer transcription start site transcription end Fig. 15-3, pp
9 Control of Transcription Chemical modifications and chromosome duplications affect RNA polymerase s access to genes Interactions between DNA and histone proteins (methylation) prevent transcription Polytene chromosomes (many copies) increase transcription rates in some organisms
10 Drosophila Polytene Chromosomes
11 Controls of mrna Transcripts mrna processing DNA splicing controls products of translation mrna transport controls delivery of transcripts Passage through nuclear pores Delivery within cytoplasm (mrna localization)
12 Translational Controls Controls over molecules involved in translation Controls over mrna stability Depends on base sequence, length of poly-a tail, and which proteins are attached to it RNA interference Expression of a microrna complementary to a gene inhibits expression of the gene
13 Post-Translational Modification Post-translational modification can inhibit, activate, or stabilize many molecules, including enzymes that participate in transcription and translocation
14 Points of Control over Eukaryotic Gene Expression
15 DNA NUCLEUS A Transcription Binding of transcription factors to special sequences in DNA slows or speeds transcription. Chemical modifications and chromosome duplications affect RNA polymerase s physical access to genes. new RNA transcript mrna B mrna Processing New mrna cannot leave the nucleus before being modified, so controls over mrna processing affect the timing of transcription. Controls over alternative splicing influence the final form of the protein. C mrna Transport RNA cannot pass through a nuclear pore unless bound to certain proteins. Transport protein binding affects where the transcript will be delivered in the cell. mrna polypeptide chain active protein CYTOPLASM D Translation An mrna s stability influences how long it is translated. Proteins that attach to ribosomes or initiation factors can inhibit translation. Doublestranded RNA triggers degradation of complementary mrna. E Protein Processing A new protein molecule may become activated or disabled by enzymemediated modifications, such as phosphorylation or cleavage. Controls over these enzymes influence many other cell activities. Stepped Art Fig. 15-2, p. 230
16 Animation: Controls of eukaryotic gene expression
17 15.1 Key Concepts: Overview of Controls Over Gene Expression A variety of molecules and processes alter gene expression in response to changing conditions both inside and outside the cell Selective gene expression also results in cell differentiation, by which different cell lineages become specialized
18 15.2 A Few Outcomes of Eukaryotic Gene Controls Selective gene expression can give rise to visible traits
19 X Chromosome Inactivation X chromosome inactivation In cells of female mammals, either the maternal or paternal X chromosome is randomly condensed (Barr body) and is inactive Occurs in an early embryonic stage, so that all descendents of that particular cell have the same inactive X chromosome, resulting in mosaic gene expression
20 X Chromosome Inactivation
21 Fig. 15-5a, p. 232
22 Fig. 15-5b, p. 232
23 Fig. 15-5c, p. 232
24 Calico: Mosaic Gene Expression in a Female Mammal
25 Animation: X-chromosome inactivation
26 Dosage Compensation Dosage compensation The theory that X chromosome inactivation equalizes expression of X chromosome genes between the sexes Mechanism of X inactivation XIST gene on one X chromosome transcribes an RNA molecule which coats the chromosome and causes it to condense, forming a Barr body
27 Flower Formation The ABC model Three sets of master genes (A,B,C) encode products that initiate cascades of expression of other genes to accomplish intricate tasks such as flower formation Master genes are expressed differently in tissues of floral shoots Master genes are switched on by environmental cues such as day length
28 Controls of Flower Formation
29 Fig. 15-7a, p. 233
30 petals carpel sepals stamens A The pattern in which the floral identity genes A, B, and C are expressed affects differentiation of cells growing in whorls in the plant s tips. Their gene products guide expression of other genes in cells of each whorl; a flower results. Fig. 15-7a, p. 233
31 Fig. 15-7b, p. 233
32 Animation: ABC model for flowering
33 15.2 Key Concepts Examples From Eukaryotes The orderly, localized expression of certain genes in embryos gives rise to the body plan of complex multicelled organisms In female mammals, most of the genes on one of the two X chromosomes are inactivated in every cell
34 15.3 There s a Fly in My Research Many important discoveries have resulted from studies of the fruit fly, Drosophila melanogaster Research with fruit flies yielded the insight that body plans are a result of patterns of gene expression in embryos
35 Discovery of Homeotic Genes Homeotic genes Master genes that control differentiation of specific tissues and body parts in an embryo Encode transcription factors with a homeodomain Homeodomain A region of about 60 amino acids that can bind to a promoter or some other sequence in DNA
36 Homeotic Gene Experiments Antennapedia
37 Fig. 15-8a, p. 234
38 Fig. 15-8b, p. 234
39 Fig. 15-8c, p. 234
40 Fig. 15-8de, p. 235
41 Fig. 15-8d, p. 235
42 Fig. 15-8e, p. 235
43 Knockout Experiments Knockout experiments Researchers inactivate a gene by introducing a mutation into it, then compare the differences with normal individuals and similar genes in humans Example: The PAX6 gene in humans is a homologue of the eyeless gene in Drosophila
44 Filling in Details of Body Plans Pattern formation As an embryo develops, cells that differentiate in different body regions migrate and form tissues, creating complex body forms from local processes driven by master genes Regional gene expression during development results in a 3-dimesional map that consists of overlapping concentrations of master gene products, which change over time
45 Gene Expression and Pattern Formation
46 Fig. 15-9a, p. 235
47 Fig. 15-9b, p. 235
48 Fig. 15-9c, p. 235
49 Fig. 15-9d, p. 235
50 Fig. 15-9e, p. 235
51 Fig. 15-9f, p. 235
52 15.3 Key Concepts Fruit Fly Development Drosophila research revealed how a complex body plan emerges All cells in a developing embryo inherit the same genes, but they activate and suppress different fractions of those genes
53 15.4 Prokaryotic Gene Control Prokaryotes are single celled and do not have master genes Prokaryotes control gene expression mainly by adjusting the rate of transcription in response to shifts in nutrient availability and other outside conditions
54 Prokaryotic Gene Control In prokaryotes, genes that are used together often occur together on chromosomes Operon A promoter and one or more operators that collectively control transcription of multiple genes Operators DNA regions that are binding sites for a repressor
55 The Lactose Operon E. coli digest lactose in guts of mammals using a set of three enzymes controlled by two operators and a single promoter (the lac operon) When lactose is not present, repressors bind to the operators and inactivate the promoter; transcription does not proceed When lactose is present, allolactose binds to the repressors; repressors don t bind to operators to inactivate the promoter; transcription proceeds
56 The Lactose Operon Repressor
57 repressor looped-up DNA looped-up DNA Fig , p. 236
58 The Lactose Operon
59 Lactose absent Lactose Operon operator promoter operator gene 1 gene 2 gene 3 Repressor protein A The lac operon in the E. coli chromosome. B In the absence of lactose, a repressor binds to the two operators. Binding prevents RNA polymerase from attaching to the promoter, so transcription of the operon genes does not occur. Lactose present lactose gene 1 gene 2 gene 3 C When lactose is present, some is converted to a form that binds to the repressor. Binding alters the shape of the repressor such that it releases the operators. RNA polymerase can now attach to the promoter and transcribe the operon genes. mrna RNA polymerase operator promoter operator gene 1 gene 2 gene 3 Fig , p. 237
60 Lactose absent Lactose Operon operator promoter operator gene 1 gene 2 gene 3 Repressor protein A The lac operon in the E. coli chromosome. B In the absence of lactose, a repressor binds to the two operators. Binding prevents RNA polymerase from attaching to the promoter, so transcription of the operon genes does not occur. Lactose present lactose gene 1 gene 2 gene 3 C When lactose is present, some is converted to a form that binds to the repressor. Binding alters the shape of the repressor such that it releases the operators. RNA polymerase can now attach to the promoter and transcribe the operon genes. mrna RNA polymerase operator promoter operator gene 1 gene 2 gene 3 Stepped Art Fig , p. 237
61 Animation: The lactose operon
62 Animation: Negative control of the lactose operon
63 Lactose Intolerance Human infants and other mammals produce the enzyme lactase, which digests the lactose in milk adults tend to lose the ability to produce lactase, and become lactose intolerant
64 15.4 Key Concepts Examples From Prokaryotes Prokaryotic gene controls govern responses to short-term changes in nutrient availability and other aspects of the environment The main gene controls bring about fast adjustments in the rate of transcription
65 Animation: Fate map
66 ABC video: Regenerative Human Organs
67 ABC video: Genetically modified cancer fighters
68 Video: Between you and eternity
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