1. Albia Dugger Miami Dade College Cecie Starr Christine Evers Lisa Starr www.cengage.com/biology/starr Chapter 10 Controls Over Genes (Sections 10.1 - 10.5)

2. 10.1 Between You and Eternity Many gene expression controls regulate cell growth and division When those controls fail, cancer results Robin Shoulla was diagnosed with breast cancer when she was seventeen

3. Cancer Cancer is a multistep process in which abnormally growing and dividing cells disrupt body tissues Cancer often begins with a mutation in a gene whose product is part of a system of controls over cell growth and division cancer Disease that occurs when uncontrolled growth of body cells physically and metabolically disrupts tissues

4. A Case of Breast Cancer Irregular clusters of cancer cells in human breast tissue

5. 10.2 Eukaryotic Gene Expression Differentiation occurs as different cell lineages begin to express different subsets of their genes Which genes a cell uses determines the molecules it will produce, which in turn determines what kind of cell it will be differentiation Process by which cells become specialized

6. Eukaryotic Gene Expression Which genes are expressed at any given time depends on many factors, such as conditions in the cytoplasm and extracellular fluid, and type of cell These factors affect controls governing all steps of gene expression, starting with transcription and ending with delivery of an RNA or protein product to its final destination Controls may start, enhance, slow, or stop gene expression

7. Control of Transcription Whether and how fast a gene is transcribed depends on which transcription factors are bound to the DNA Activators speed transcription by binding to DNA enhancers Repressors slow or stop transcription

8. Key Terms transcription factor Regulatory protein that influences transcription; e.g. an activator or repressor activator Regulatory protein that increases the rate of transcription when it binds to a promoter or enhancer enhancer Binding site in DNA for proteins that enhance transcription rate repressor Regulatory protein that blocks transcription

9. Control of Transcription (cont.) Interactions between DNA and histone proteins also affect transcription Molecules that methylate DNA prevent transcription Number of gene copies affects how fast its product is made Polytene chromosomes consists of hundreds or thousands of copies of the same DNA molecule

10. Drosophila Polytene Chromosomes Giant polytene chromosomes form in Drosophila salivary gland cells by repeated DNA replication Transcription is visible (white arrows) where DNA has loosened

11. mRNA Processing Before eukaryotic mRNAs leave the nucleus, they are modified—spliced, capped, and finished with a poly-A tail Controls over these modifications can affect the form of a protein product and when it will appear in the cell

12. Translational Control Most controls over eukaryotic gene expression affect translation Many controls govern the production or function of various molecules that carry out translation Others affect mRNA stability: Depends on base sequence, length of poly-A tail, and which proteins are attached to it

13. Post-Translational Modification Many newly-synthesized polypeptide chains must be modified before they become functional Post-translational modifications inhibit, activate, or stabilize many molecules, including the enzymes that participate in transcription and translation

14. Fig 10.2, p. 152 new RNA transcript mRNA Nucleus DNA active protein polypeptide chain Cytoplasm mRNA 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. 1 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. 2 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. 3 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. 4 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. 5 Stepped Art Points of Control Over Eukaryotic Gene Expression

15. Key Concepts Gene Control in Eukaryotes 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 differentiation, by which cell lineages become specialized

16. 10.3 There’s a Fly in My Research The fruit fly Drosophila melanogaster has been the subject of of many research experiments on eukaryotic gene expression It reproduces quickly and has a short life cycle

17. Homeotic Genes Homeotic genes encode transcription factors with a homeodomain – a region of about sixty amino acids that can bind to a promoter or some other DNA sequence in a chromosome homeotic gene Type of master gene Its expression controls formation of specific body parts during development

18. Master Genes Master genes affect the expression of many other genes. Expression of a master gene causes other genes to be expressed, allowing completion of intricate tasks such as eye formation during embryonic development master gene Gene encoding a product that affects the expression of many other genes

19. Knockouts Researchers inactivate a homeotic gene by introducing a mutation or deleting it entirely (knockout) Any differences in an organism with a knocked-out gene may be clues to the function of the missing gene product knockout An experiment in which a gene is deliberately inactivated in a living organism

20. Homeotic Genes: Eyes and eyeless A normal fruit fly, a fruit fly with eyeless mutation, and expression of eyeless on a fly’s head and wing

21. Homeotic Genes: PAX6 Humans and other animals have a gene similar to eyeless A mutation in PAX6 results in missing irises (aniridia)

22. Filling in Details of Body Plans As an embryo develops, its differentiating cells form tissues, organs, and body parts Some cells alternately migrate and stick to other cells to develop structures that weave through tissues These events fill in the body’s details, and are driven by cascades of master gene expression

23. Pattern Formation Pattern formation determines the body plan of an embryo: Protein products diffuse in gradients along the embryo Cells translate different master genes, depending on where they fall within those gradients Some master gene products cause undifferentiated cells to differentiate into specialized tissues pattern formation Process by which a complex body forms from local processes during embryonic development

24. Pattern Formation in a Fruit Fly The master gene even-skipped is expressed (red) where two gene products (blue and green) overlap

25. Pattern Formation in a Fruit Fly Products of several master genes confine expression of even- skipped (red) to seven stripes, where segments develop

26. Key Concepts Mechanisms of Control All cells in an embryo inherit the same genes, but they start using different subsets of those genes during development The orderly, localized expression of master genes gives rise to the body plan of complex multicelled organisms

27. 10.4 Outcomes of Gene Controls Many traits of humans and other eukaryotic organisms arise as an outcome of gene expression controls Examples: X-chromosome inactivation Male sex determination Flower formation

28. X Chromosome Inactivation A female’s cells each contain two X chromosomes, one inherited from her mother, the other from her father One X chromosome is always tightly condensed (Barr bodies) This X chromosome inactivation ensures that only one of the two X chromosomes in a female’s cells is active According to the dosage compensation theory, this equalizes expression of X chromosome genes between sexes

29. Key Terms X chromosome inactivation Shutdown of one of the two X chromosomes in the cells of female mammals Caused by transcription of the XIST gene which keeps the chromosome from transcribing other genes dosage compensation Theory that X chromosome inactivation equalizes gene expression between males and females

30. X Chromosome Inactivation Barr bodies (red spots) in nuclei of XX cells, compared to nuclei of XY cells

31. Male Sex Determination in Humans The human Y chromosome carries the SRY gene—the master gene for male sex determination in mammals An early human embryo appears neither male nor female SRY expression in XY embryos triggers formation of testes (male gonads) that secrete testosterone, which initiates development of other male traits In an XX embryo, ovaries form in the absence of the Y chromosome and its SRY gene

32. Fig 10.8, p. 156 birth approaching vaginal opening no SRY present Structures that will give rise to external genitalia appear at seven weeks penis SRY expressed Developing Reproductive Organs

33. Flower Formation Activation of three sets of master genes (A, B, and C) guide flower formation – the differentiation of leaf cells into floral parts (sepals, petals, stamens, and carpels) These genes are switched on by environmental cues such as seasonal changes in the length of night

34. Fig 10.9a, p. 157 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. stamens petalscarpel sepals Control of Flower Formation

35. Fig 10.9b, p. 157 B Mutations in Arabidopsis ABC genes result in malformed flowers. Top left, right: A gene mutations lead to petal-less flowers with no structures in place of missing petals. Bottom left: B gene mutations lead to flowers with sepals instead of petals. Bottom right: C gene mutations lead to flowers with petals instead of sepals and carpels. Compare the normal flower in A. Mutations in Arabidopsis thaliana

36. Key Concepts Examples in Eukaryotes One of the two X chromosomes is inactivated in every cell of female mammals The Y chromosome carries a master gene that causes male traits to develop in the human fetus Flower development is orchestrated by a set of homeotic genes

37. 10.5 Gene Control in Bacteria Bacteria and archaea do not use master genes Bacteria control gene expression mainly by adjusting the rate of transcription Genes that are used together often occur together on the chromosome – all are transcribed together, so their transcription is controllable in a single step

38. The Lactose Operon E. coli uses three enzymes whose genes are transcribed together to break down lactose molecules Unless lactose is present, these genes are turned off There is one promoter for all three genes A promoter and one or more operators that control transcription of multiple genes are called an operon

39. Key Terms operon Group of genes together with a promoter–operator DNA sequence that controls their transcription Occur in bacteria, archaeans, and eukaryotes operator Part of an operon; a DNA binding site for a repressor which stops transcription

40. The Lactose Operon (1) The operon consists of a promoter flanked by two operators, and three genes for lactose-metabolizing enzymes (2) In the absence of lactose, a repressor binds the two operators, preventing RNA polymerase from attaching to the promoter – transcription does not occur (3) When lactose is present, some binds to the repressor, altering the shape of the repressor so it releases the operators – RNA polymerase attaches to the promoter and transcribes the genes

41. Fig 10.10, p. 158 The lac operon in the E. coli chromosome. 1 Stepped Art 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. Repressor protein 2 Lactose absent 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. Lactose present lactose 3 The Lactose Operon

42. Key Concepts Gene Control in Bacteria Bacterial 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

43. Lactose Intolerance In most people, production the enzyme lactase (which digests lactose in food) starts declining at age five The inability to produce lactase is called lactose intolerance People who carry a mutation in one of the genes responsible for programmed lactase shutdown make enough lactase to continue drinking milk without problems into adulthood