1. © 2013 Pearson Education, Inc. Lectures by Edward J. Zalisko PowerPoint ® Lectures for Campbell Essential Biology, Fifth Edition, and Campbell Essential Biology with Physiology, Fourth Edition – Eric J. Simon, Jean L. Dickey, and Jane B. Reece Chapter 11 How Genes Are Controlled

2. © 2010 Pearson Education, Inc. HOW AND WHY GENES ARE REGULATED Every somatic cell in an organism contains identical genetic instructions. –They all share the same genome. –So what makes them different? In cellular differentiation, cells become specialized in –Structure –Function Certain genes are turned on and off in the process of gene regulation.

3. © 2010 Pearson Education, Inc. Patterns of Gene Expression in Differentiated Cells In gene expression –A gene is turned on and transcribed into RNA –Information flows from –Genes to proteins –Genotype to phenotype Information flows from DNA to RNA to proteins. The great differences among cells in an organism must result from the selective expression of genes.

4. © 2010 Pearson Education, Inc. Gene Regulation in Bacteria Natural selection has favored bacteria that express –Only certain genes –Only at specific times when the products are needed by the cell So how do bacteria selectively turn their genes on and off?

5. © 2010 Pearson Education, Inc. An operon includes –A cluster of genes with related functions –The control sequences that turn the genes on or off The bacterium E. coli used the lac operon to coordinate the expression of genes that produce enzymes used to break down lactose in the bacterium’s environment.

6. © 2010 Pearson Education, Inc. The lac operon uses –A promoter, a control sequence where the transcription enzyme initiates transcription –An operator, a DNA segment that acts as a switch that is turned on or off –A repressor, which binds to the operator and physically blocks the attachment of RNA polymerase

7. Operon turned on (lactose inactivates repressor) Lactose Protein mRNA Lactose enzymes DNA Protein mRNA DNA Operon turned off (lactose absent) Translation Inactive repressor RNA polymerase bound to promoter Transcription Active repressor RNA polymerase cannot attach to promoter Regulatory gene Promoter Operator Operon Genes for lactose enzymes

8. © 2010 Pearson Education, Inc. Gene Regulation in Eukaryotic Cells Eukaryotic cells have more complex gene regulating mechanisms with many points where the process can be regulated, as illustrated by this analogy to a water supply system with many control valves along the way.

9. DNA Flow of mRNA through nuclear envelope Processing of RNA Transcription of gene Unpacking of DNA Chromosome Gene RNA transcript IntronExon mRNA in nucleus Tail Cap mRNA in cytoplasm Nucleus Cytoplasm Breakdown of mRNA Translation of mRNA Breakdown of protein Various changes to polypeptide Active protein Polypeptide

10. © 2010 Pearson Education, Inc. The Initiation of Transcription The initiation of transcription is the most important stage for regulating gene expression. In prokaryotes and eukaryotes, regulatory proteins –Bind to DNA –Turn the transcription of genes on and off Unlike prokaryotic genes, transcription in eukaryotes is complex, involving many proteins, called transcription factors, that bind to DNA sequences called enhancers.

11. Bend in the DNA Enhancers (DNA control sequences) Transcription factor Transcription Promoter Gene RNA polymerase

12. © 2010 Pearson Education, Inc. Repressor proteins called silencers –Bind to DNA –Inhibit the start of transcription Activators are –More typically used by eukaryotes –Turn genes on by binding to DNA

13. © 2010 Pearson Education, Inc. RNA Processing and Breakdown The eukaryotic cell –Localizes transcription in the nucleus –Processes RNA in the nucleus RNA processing includes the –Addition of a cap and tail to the RNA –Removal of any introns –Splicing together of the remaining exons In alternative RNA splicing, exons may be spliced together in different combinations, producing more than one type of polypeptide from a single gene.

14. RNA transcript Exons RNA splicing mRNA DNA or 1 2 3 5 1 2 4 5 1 2 3 4 1 2 3 5 5 4

15. © 2010 Pearson Education, Inc. The Initiation of Translation The process of translation offers additional opportunities for regulation. Post-translational control mechanisms –Occur after translation –Often involve cutting polypeptides into smaller, active final products The selective breakdown of proteins is another control mechanism operating after translation.

16. Initial polypeptide Cutting Insulin (active hormone) The Formation Of An Active Insulin Molecule

17. © 2010 Pearson Education, Inc. Cell Signaling In a multicellular organism, gene regulation can cross cell boundaries. A cell can produce and secrete chemicals, such as hormones, that affect gene regulation in another cell.

18. SIGNALING CELL mRNA Plasma membrane Signal molecule Secretion Receptor protein Transcription factor (activated) Reception Signal transduction pathway TARGET CELL Nucleus Transcription Response Translation New protein

19. CLONING PLANTS AND ANIMALS The Genetic Potential of Cells Differentiated cells –All contain a complete genome –Have the potential to express all of an organism’s genes Differentiated plant cells can develop into a whole new organism. © 2010 Pearson Education, Inc.

20. Adult plant Young plant Cell division in culture Root cells in growth medium Root of carrot plant Single cell Test-tube Cloning Of A Carrot Plant

21. © 2010 Pearson Education, Inc. The somatic cells of a single plant can be used to produce hundreds of thousands of clones. Plant cloning –Demonstrates that cell differentiation in plants does not cause irreversible changes in the DNA –Is now used extensively in agriculture

22. © 2010 Pearson Education, Inc. Regeneration –Is the regrowth of lost body parts –Occurs, for example, in the regrowth of the legs of salamanders

23. © 2010 Pearson Education, Inc. Reproductive Cloning of Animals Nuclear transplantation –Involves replacing nuclei of egg cells with nuclei from differentiated cells –Has been used to clone a variety of animals In 1997, Scottish researchers produced Dolly, a sheep, by replacing the nucleus of an egg cell with the nucleus of an adult somatic cell in a procedure called reproductive cloning, because it results in the birth of a new animal.

24. Donor cell Nucleus from donor cell Remove nucleus from egg cell Add somatic cell from adult donor Grow in culture to produce an early embryo Remove embryonic stem cells from embryo and grow in culture Induce stem cells to form specialized cells for therapeutic use Implant embryo in surrogate mother Clone of donor is born Reproductive cloning Therapeutic cloning Cloning By Nuclear Transplantation

25. © 2010 Pearson Education, Inc. Other mammals have since been produced using this technique including –Farm animals –Control animals for experiments –Rare animals in danger of extinction Practical Applications of Reproductive Cloning

26. © 2010 Pearson Education, Inc. Human Cloning Cloning of animals –Has heightened speculation about human cloning –Is very difficult and inefficient Critics raise practical and ethical objections to human cloning.

27. (a) The first cloned cat (right) (c) Clones of endangered animals (b) Cloning for medical use Gray wolf Gaur Banteng Mouflon calf with mother Figure 11.14

28. © 2010 Pearson Education, Inc. Therapeutic Cloning and Stem Cells The purpose of therapeutic cloning is not to produce a viable organism but to produce embryonic stem cells.

29. © 2010 Pearson Education, Inc. Embryonic Stem Cells Embryonic stem cells (ES cells) –Are derived from blastocysts –Can give rise to specific types of differentiated cells

30. © 2010 Pearson Education, Inc. Adult stem cells –Are cells in adult tissues –Generate replacements for nondividing differentiated cells Unlike embryonic ES cells, adult stem cells –Are partway along the road to differentiation –Usually give rise to only a few related types of specialized cells Adult Stem Cells

31. Adult stem cells in bone marrow Cultured embryonic stem cells Different culture conditions Different types of differentiated cells Heart muscle cells Nerve cells Blood cells

32. © 2010 Pearson Education, Inc. THE GENETIC BASIS OF CANCER In recent years, scientists have learned more about the genetics of cancer. As early as 1911, certain viruses were known to cause cancer. Oncogenes are –Genes that cause cancer –Found in viruses

33. © 2010 Pearson Education, Inc. Oncogenes and Tumor-Suppressor Genes Proto-oncogenes are –Normal genes with the potential to become oncogenes –Found in many animals –Often genes that code for growth factors, proteins that stimulate cell division For a proto-oncogene to become an oncogene, a mutation must occur in the cell’s DNA.

34. © 2010 Pearson Education, Inc. For a proto-oncogene to become an oncogene, a mutation must occur in the cell’s DNA.

35. New promoter Normal growth- stimulating protein in excess Normal growth- stimulating protein in excess Hyperactive growth- stimulating protein Gene moved to new DNA position, under new controls Multiple copies of the gene DNA Mutation within the gene Proto-oncogene (for protein that stimulates cell division) Oncogene How A Proto-oncogene Can Become An Oncogene

36. © 2010 Pearson Education, Inc. Tumor-suppressor genes –Inhibit cell division –Prevent uncontrolled cell growth –May be mutated and contribute to cancer

37. Defective, nonfunctioning protein Cell division under control (b) Uncontrolled cell growth (cancer) Normal growth- inhibiting protein Cell division not under control (a) Normal cell growth Tumor-suppressor gene Mutated tumor-suppressor gene

38. Second tumor-suppressor gene inactivated Tumor-suppressor gene inactivated Oncogene activated DNA changes: Cellular changes: Increased cell division Growth of benign tumor Growth of malignant tumor Colon wall Stepwise Development Of A Typical Colon Cancer

39. © 2010 Pearson Education, Inc. The development of a malignant tumor is accompanied by a gradual accumulation of mutations that –Convert proto-oncogenes to oncogenes –Knock out tumor-suppressor genes

40. © 2010 Pearson Education, Inc. “Inherited” Cancer Most mutations that lead to cancer arise in the organ where the cancer starts. In familial or inherited cancer –A cancer-causing mutation occurs in a cell that gives rise to gametes –The mutation is passed on from generation to generation

41. © 2010 Pearson Education, Inc. Breast cancer –Is usually not associated with inherited mutations –In some families can be caused by inherited, BRCA1 cancer genes

43. © 2010 Pearson Education, Inc. Cancer Risk and Prevention Cancer –Is one of the leading causes of death in the United States –Can be caused by carcinogens, cancer-causing agents found in the environment, including –Tobacco products –Alcohol –Exposure to ultraviolet light from the sun Exposure to carcinogens –Is often an individual choice –Can be avoided Some studies suggest that certain substances in fruits and vegetables may help protect against a variety of cancers.