1. Gene Expression and Control Chapter 7 Part 2

2. 7.6 Mutated Genes and Their Products  Mutations are permanent changes in the nucleotide sequence of DNA, which may alter a gene product  A mutation that changes a gene’s product may have harmful effects Example: Mutations that affect the proteins in hemoglobin reduce blood’s ability to carry oxygen

3. Types of Mutations  Deletion Mutation in which one or more base pairs are lost  Insertion Mutation in which one or more base pairs become inserted into DNA  Base-pair substitution Type of mutation in which a single base-pair changes

4. Two Common Mutations in Hemoglobin

5. Fig. 7-9a, p. 125 A Hemoglobin, an oxygen-transport protein in red blood cells. This protein consists of four globin chains: two alpha chains (blue) and two beta chains (green). Each globin chain folds up to form a pocket that cradles a type of cofactor called a heme (red). Oxygen binds to the iron atom at the center of each heme group.

6. Fig. 7-9b, p. 125 part of DNA mRNA transcribed from DNA threonine (thr) proline (pro) glutamic acid (glu) lysine (lys) resulting amino acid sequence B Part of the DNA, mRNA, and amino acid sequence of the beta chain of a normal hemoglobin molecule.

7. Fig. 7-9c, p. 125 deletion in DNA altered mRNA threonine (thr) proline (pro) glycine (gly) arginine (arg) threonine (thr) altered amino acid sequence C A single base-pair deletion causes the reading frame for the rest of the mRNA to shift, so a completely different protein product forms. This mutation results in a defective globin chain. The outcome is thalassemia, a genetic disorder in which a person has an abnormally low amount of hemoglobin.

8. Fig. 7-9d, p. 125 base-pair substitution in DNA altered mRNA threonine (thr) proline (pro) valine (val) glutamic acid (glu) lysine (lys) altered amino acid sequence D A base-pair substitution in DNA replaces a thymine with an adenine. When the altered mRNA is translated, valine replaces glutamate as the sixth amino acid of the new polypeptide chain. Hemoglobin with this chain is called HbS, or sickle hemoglobin.

9. Base-pair substitution

10. Fig. 7-10a, p. 126 valine (val) histidine (his) leucine (leu) threonine (thr) proline (pro) glutamic acid (glu) glutamic acid (glu) 1 Normal amino acid sequence at the start of the hemoglobin beta chain. valine (val) histidine (his) leucine (leu) threonine (thr) proline (pro) valine (val) glutamic acid (glu) 2 One amino acid substitution results in the abnormal beta chain of sickle hemoglobin (HbS). The sixth amino acid in such chains is valine, not glutamic acid. sickled cell 3 Glutamic acid carries an overall negative charge; valine carries no charge. This difference causes the protein to behave differently. At low oxygen levels, HbS molecules stick together and form rod-shaped clumps that distort normally round red blood cells into sickle shapes. (A sickle is a farm tool with a crescent-shaped blade.) normal cell 4 Tionne “T-Boz” Watkins of the music group TLC is a celebrity spokesperson for the Sickle Cell Disease Association of America. She was diagnosed with sickle-cell anemia as a child. Sickle-Cell Anemia: A Base-Pair Substitution

11. Fig. 7-10b, p. 126

12. What Causes Mutations?  Most mutations result from unrepaired DNA polymerase errors during DNA replication  Some result from transposable element activity, or from exposure to radiation or chemicals  Transposable element Small segment of DNA that can spontaneously move to a new location in a chromosome

13. Ionizing Radiation Damage  Ionizing radiation (x-rays) breaks chromosomes and produces free radicals

14. Nonionizing Radiation Damage  Nonionizing radiation (UV light) results in thymine dimers, which lead to skin cancer

15. Fig. 7-11b, p. 127 thymine dimer

16. Environmental Damage  Some natural and synthetic chemicals cause mutations in DNA  Example: Cigarette smoke transfers small hydrocarbon groups to bases in DNA, causing mispairing during replication

17. Frameshift mutation

18. Duplication

19. Deletion

20. Inversion

21. Translocation

22. Sickle-cell anemia

23. 7.7 Examples of Eukaryotic Gene Controls  All cells in your body carry the same DNA  Some genes are transcribed by all cells, but most cells are specialized (differentiated) to use only certain genes  Which genes are expressed at a given time depends on the type of cell and conditions

24. Cell Differentiation  Cells differentiate when they start expressing a unique subset of their genes – controls over gene expression are the basis of differentiation  Differentiation The process by which cells become specialized Occurs as different cell lineages begin to express different subsets of their genes

25. Controlling Gene Expression  Controlling gene expression is critical for normal development and function of a eukaryotic body  All steps between transcription and delivery of gene product are regulated  Transcription factor Protein that influences transcription by binding to DNA

26. Homeotic Genes  Homeotic gene Type of master gene that controls formation of specific body parts during development  Master gene Gene encoding a product that affects the expression of many other genes Controls an intricate task such as eye formation

27. Homeodomains  All homeotic genes encode transcription factors with a homeodomain – a region of about 60 amino acids that can bind to a promoter or some other DNA sequence

28. Identifying Homeotic Genes and Their Functions  Researchers study the function of a homeotic gene by altering its expression – by introducing a mutation or deleting it entirely Examples: eyeless, dunce, tinman, groucho  Gene knockout A gene that has been inactivated in an organism

29. Gene Knockout Experiment: Eyeless

30. Fig. 7-12a, p. 128

31. Fig. 7-12b, p. 128

32. Fig. 7-12c, p. 128

33. PAX6 Gene Function  Many master genes are interchangeable among species; in humans and many other animals, the PAX6 gene affects eye formation

34. Sex Chromosome Genes  In mammals, males have only one X chromosome – females have two, but one is tightly condensed into a Barr body and inactive  Dosage compensation Theory that X chromosome inactivation equalizes gene expression between males and females

35. X Chromosome Inactivation  Female cells have Barr bodies, male cells do not

36. The Y Chromosome  The SRY gene, found on the Y chromosome, is the master gene for male sex determination Triggers formation of testes Testosterone produced by testes controls formation of male secondary traits  Absence of SRY gene in females triggers development of ovaries, female characteristics

37. Fig. 7-14, p. 129 Structures that will give rise to external genitalia appear at seven weeks SRY expressedno SRY present penis vaginal opening birth approaching Development of Human Reproductive Organs

38. Cancer: Gene Expression Out of Control  Many gene expression controls regulate cell growth and division – mutations that disrupt normal controls can cause cancer  Cancer Disease that occurs when a malignant neoplasm physically and metabolically disrupts body tissues

39. Tumors  Tumor Abnormally growing and dividing mass of cells  Metastasis A process of cancer in which tumor cells lose membrane recognition proteins, break free, and establish themselves in other parts of the body

40. Cancer and Mutations  Cancer begins with a mutation in a gene whose product controls cell growth and division  A mutation that causes cancer may be inherited or be caused by environmental agents  Tumors are more likely to occur when mutations occur in tumor suppressor genes, such as BRCA1 and BRCA2

41. BRCA Genes and Cancer

42. Fig. 7-15b, p. 130 normal cells in organized clusters irregular clusters of cancer cells

43. Controls of eukaryotic gene expression

44. Fate map

45. X-chromosome inactivation

46. Protein synthesis summary

47. 7.8 Impacts/Issues Revisited  Ricin causes ribosomes to stop working – protein synthesis stops, and the cell quickly dies  Researchers are trying to kill cancer cells without harming normal cells by attaching ricin to an antibody that can find cancer cells in the body

48. Digging Into Data: BRCA Mutations in Women Diagnosed with Breast Cancer