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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