Chapter 10 Gene Control

1. Chapter 10Gene Control

2. 10.1 Between You and Eternity • Cancer is a multistep process in which cells grow and divide abnormally, disrupting physical and metabolic functions • More than 200,000 new cases of breast cancer are diagnosed in the US each year – about 5,700 in women and men under thirty-four years of age • Mutations in genes that control cell growth and division predispose individuals to develop certain kinds of cancer

3. normal cells in organized clusters disorganized clusters of malignant cells Figure 10-1b p163

4. 10.2 Switching Genes Off and On • All body cells contain the same DNA with the same genes • Gene controls govern the kinds and amounts of substances in a cell at any given time • Various control processes regulate all steps between gene and gene product

5. Cell Differentiation • 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. Gene Controls • Control over which genes are expressed at a particular time is crucial for proper development • Gene controls start, enhance, slow, or stop the individual steps of gene expression • Gene controls can operate at any step in the path of protein production

7. Nucleus 1 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. DNA new RNA transcript 2 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. mRNA 3 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. Cytoplasm 4 Translation An mRNA’s stability influences how long it is translated. Proteins that attach to ribosomes or initiation factors can inhibit translation. Double-stranded RNA triggers degradation of complementary mRNA. mRNA polypeptide chain 5 Protein Processing A new protein molecule may become activated or disabled by enzyme-mediated modifications, such as phosphorylation or cleavage. Controls over these enzymes influence many other cell activities. active protein Stepped Art Figure 10-2 p164

8. 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 • Repressorsslow or stop transcription

9. Control of Transcription (cont.) • Chromatin structure also affects transcription • Chemical modifications and chromosome duplications affect RNA polymerase’s access to genes • Enzymes that acetylate histones encourage transcription • Adding a methyl group to a histone prevent transcription • Polytene chromosomes (many copies) increase transcription rates in some organisms

10. 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)

11. Translational Controls • 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

12. Post-Translational Modification • Post-translational modification can inhibit, activate, or stabilize many molecules, including enzymes that participate in transcription and translocation

13. Take-Home Message:What is gene control? • Gene controls consist of molecules and structures that can start, enhance, slow, or stop individual steps of gene expression • Most cells of multicelled organisms differentiate as they start expressing a unique subset of their genes; which genes a cell expresses depends on the type of organism, its stage of development, and environmental conditions

14. 10.3 Master Genes • Cascades of gene expression govern the development of a complex, multicelled body • Master genes encode products that affect the expression of many other genes • Pattern formation is the process by which a complex body forms from local processes in an embryo

15. Gene Expression Control in a Fly

16. 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

17. A Homeodomain

18. 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

19. Eyeless

20. Take-Home Message:How do genes control development? • Development is orchestrated by cascades of master gene expression in embryos • The expression of homeotic genes during development governs the formation of specific body parts; homeotic genes that function in similar ways across taxa are evidence of shared ancestry

21. 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

22. Inactivated X Chromosomes

23. Mosaic Tissues in a Human Female

24. 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

25. Male Sex Determination in Humans • Most of the 1,336 genes on the X chromosome determine nonsexual traits such as blood clotting and color perception • The human Y chromosome carries 307 genes, including SRY – the master gene that triggers formation of testes in males • Testosterone produced by the testes causes formation of male genitalia and secondary sexual traits • In the absence of testosterone, female genitalia form

26. Structures that will give rise to external genitalia appear at seven weeks SRY expressed no SRY present penis vaginal opening birth approaching Figure 10-8 p168

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. 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. Figure 10-9a p168

29. Figure 10-9b p168

30. Take-Home Message: What are some examples of gene control in eukaryotes? • X chromosome inactivation balances expression of X chromosome genes between female (XX) and male (XY) mammals • SRY gene expression triggers the development of male traits in mammals • In plants, expression of ABC master genes governs development of the specialized parts of a flower

31. ANIMATION: X-chromosome inactivation To play movie you must be in Slide Show Mode PC Users: Please wait for content to load, then click to play Mac Users: CLICK HERE

32. 10.5 Gene Control in Prokaryotes • Prokaryotes (bacteria and archaea) 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

33. 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

34. Lactose Intolerance • Human infants and other mammals produce the enzyme lactase, which digests the lactose in milk • Humans begin to lose the ability to produce lactase, around age 5, and become lactose intolerant • Many people of European ancestry carry a mutation in one of the genes responsible for programmed lactase shutdown

35. Riboswitches • Some bacterial mRNAs regulate their own translation with riboswitches – small sequences of RNA nucleotides that bind to a target molecule • Binding of an end product (such as vitamin B12) changes the shape of the mRNA so that ribosomes no longer attach to it, and translation stops – an example of feedback inhibition

36. Take-Home Message:Do bacteria control gene expression? • In bacteria, the main gene expression controls regulate gene expression in response to shifts in nutrient availability and other environmental conditions • Prokaryotes can regulate gene expression using operons and riboswitches

37. DNA Methylations • Direct methylation of DNA suppresses gene expression in a more permanent manner than histone modification • Example: The active X chromosome in cells of female mammals does not express the XIST gene because its promoter is heavily methylated • Cancer is often associated with the loss of methylation, which suppresses the activity of transposable elements

38. DNA Methylations • Between 3 and 6 percent of DNA in body cells is methylated • Methyl groups often attach to a cytosine followed by a guanine, but which cytosines are methylated varies by individual • In some cases, a decrease in methylations that results in an increase in expression of a gene may offer a survival advantage

39. Heritable Methylations • Once a base in a cell’s DNA becomes methylated, it usually stays methylated in all of the cell’s descendants • Methylation patterns in parental chromosomes are normally “reset” in the first cell of the new individual, with new methyl groups being added and old ones being removed • However, not all parental methyl groups are removed, so methylations acquired during an individual’s lifetime can be passed to future offspring

40. Epigenetic Inheritance • Any heritable changes in gene expression that are not due to changes in DNA sequence are said to be epigenetic • Epigenetic inheritance can adapt offspring to environmental stressors much more quickly than evolutionary processes • Epigenetic marks may persist for generations after an environmental stressor has faded • Effects are sex-limited: boys are affected by lifestyle of male ancestors; girls, by individuals in the maternal line

41. Examples of Epigenetic Inheritance • Grandsons of boys who endured a winter of famine when they were 6 years old lived about 32 years longer than the grandsons of boys who overate at the same age • Nine-year-old boys whose fathers smoked cigarettes before age 11 are very overweight compared with boys whose fathers did not smoke in childhood