1. Chapter 13 Regulation of Gene Activity

2. Consider that....
Every cell of the body contains ALL the DNA for the organism.
Not all genes are necessary all the time
Cells must then have the ability to turn a gene on and off
ENTER:  THE OPERON MODEL 
OF GENE EXPRESSION
Operon System: genetic regulatory system found in bacteria and their viruses that allows protein synthesis to be controlled and coordinated in response to the needs of the cell
Basically - Gene control system in bacteria and viruses

3. Francois Jacob and Jacques Monod
Experiments with E. Coli showed that it is capable of regulating the expression of its genes
An operon consists of the following elements
1.  Promoter   -  where RNA polymerase attaches, signaling the start of the gene
2.  Operator  -  where a repressor binds, stopping the transcription of that gene
3.  Structural Genes - genes coding for the enzyme, they are transcribed as a unit
Repressor: protein that inhibits expression of a gene

4. Repressors versus Inducers
repressor operon: turns transcription OFF
it is normally on but can be turned off when tyrptophan is present ex: Tryp operon
inducer operon: turns transcription ON
is normally off but can be turned on when lactose is present
ex: lac operon
Grammar Time
A woman is pregnant and the baby is late.  The doctor says they will "INDUCE" labor tomorrow.  What does he mean?

5. What does this shirt mean?

6. trp Operon
It exists in the "on" state and controls the production of tryptophan.
If tryptophan is already present, it binds to the repressor and turns off- prevents more tryptophan from being made

8. lac Operon
This region is normally in the "off" position, it turns on when lactose is present (low glucose)

9. http://highered. mcgraw-hill

10. +
3 min to end

11. Tying it All Together: Lac Operon

12. (NOT a QOD, just think about and do) 1
(NOT a QOD, just think about and do) 1. All cells contain a complete copy of DNA (to start), so what make one cell different form another? 2.

13. Stem Cells: undifferentiated cells
Once cells differentiated, certain parts of the DNA are “turned off” depending on the cell function.

14. In eukaryotes, a variety of mechanisms regulate gene expression
1.  chromatin structure
2.  transcriptional control 3. post transcriptional control
4.  translational control
5.  post translational control

15. 1. Chromatin Structure
DNA is wound around a core of eight protein molecules, the result resembles beads on a string. The protein molecules are histones and each individual bead is called a nucleosome

16. Chromatin continued…
Heterochromatin: tightly coiled, inaccessible to RNA polymerase (barr bodies)
Euchromatin: loosely packed, associated with active genes
-access regulated by histones

17. BARR BODIES: inactive X chromosome in a female somatic cell
In females, chromatin of one of the X chromosomes inactivates, this inactive chromosome is called a BARR BODY
Evidence for barr bodies
1.  Women who are heterozygous for duchenne muscular dystrophy have patches of muscle tissue that are degenerative
2.  Women who are heterozygous for a condition that causes no sweat glands have patches of skin that are normal, and patches that lack sweat glands

18. Case Study - Calico Cats
Chromosomes & Inheritance
Big Question 1: Why are there no male calico cats?
Cat coloration is actually more complex than just the tri-colors found in calicos, but for the purpose of this study, we will focus only on this one aspect of cat coloration.

19. CC (Carbon Copy)
Rainbow
Big Question 2: Why do CC and Rainbow not look exactly alike, even though they are clones?

20. Shown is a human karyotype which contains
Genes are found on chromosomes, in most cases, you receive 2 alleles.
Shown is a human karyotype which contains
22 pairs of autosomes
1 pair of sex chromosomes
1. When would a person only have 1 allele for a trait?

21. Cat Karyotype 2. How is it similar to the human karyotype?
How is it different?

22. Alleles are codominant
The genes for coat color in cats are located on the X chromosome.
Alleles can be:
Orange or Black
Alleles are codominant
3. What is Spaz’s genotype?

23. There are some rare cases of male calico cats.
Weird!

24. During meiosis, each egg and sperm should receive only one copy of each chromosome (haploid)
4. Examine the graphic, describe (in words) what nondisjunction is.

25. 8. What do male calico cats, children with Down syndrome and children with Turner syndrome all have in common?

26. Big Question 2: Why do CC and Rainbow look different even though they are clones?
Consider how color is expressed on a calico cat.
Some areas express orange, some black….
It seems oddly random.

27. A Barr body (named after discoverer Murray Barr) is the inactive X chromosome in a female somatic cell, rendered inactive in a process called lyonization, in those species in which sex is determined by the presence of the Y

28. 10. How do Barr Bodies explain CC and Rainbow?
CC (Carbon Copy)
Rainbow

29. Barr Body in Cats

31. 11. Consider a male calico cat
11. Consider a male calico cat. Do you think this calico would have cognitive disabilities similar to those found in children with Down Syndrome. Why or Why not?
Possible answers: Considering that one chromosome is inactivated, it is unlikely that the cat will have a disability because the inactivation leads to each cell having the correct number. Since the extra chromosome is a sex chromosome and not an autosome, it will not have the same effect on cognitive development.

32. Genotype:     XB XO
The black patches are XB and the orange patches are XO, the cat is multicolored because not all X's are activated

33. Methylation: addition of a methyl group (to DNA) that alter the expression of genes- turning them off

34. What is Epigenetics?
When pattern of inheritance does not depend on genes
(environmental influences)
See this article from Learn.Genetics
Video at Nova narrated by Neil DeGrasse Tyspon :35

35. In eukaryotes, a variety of mechanisms regulate gene expression
1.  chromatin structure
2.  transcriptional control 3. post transcriptional control
4.  translational control
5.  post translational control

36. 2. Transcriptional control
Transcription can be promoted or repressed:
Need the correct combination of transcription factors, proteins that regulate transcription, to start gene transcription
Transcription activator: Bind to promoter and increase gene transcription

37. 3. Posttranscriptional Control
Occurs in nucleus
Includes alternative mRNA splicing
- pre-mRNA introns removed

38. 4. Translational Control
Occurs in cytoplasm
Certain microRNAs present in the cytoplasm can affect the 5’ cap or ploy-A tail at the 3’ end and alter translation

39. 5. Posttranslational Control
- Protein synthesis and activation (folding)

40. Summary: gene control/ regulation
Prokaryotic: Operon system (lac and tryp operon)
Eukaryotic:
1.  chromatin structure: histones: Heterochromatin (bar bodies) and Euchromatin, methylation,
2.  transcriptional control: transcription factors, activator, promotor
3. post transcriptional control: rna splicing
4.  translational control: cap or tail (delay translation)
5.  post translational control: folding

41. What are the types of mutations?
(just think about it, this is not a QOD)

42. Spontaneous vs Induced mutation
Occur “on their own”: vs. due to exposure to mutagens
Spontaneous often have an unknown background, may be genetic
Mutagens:
-Physical agents: X-rays, UV-rays, α, β and γ-rays.
-Chemical agents: Mustard gas, Ethylene amine, Colchicine, Ethyl-methyl sulphonate(EMS)

43. Gene Mutations

44. Point Mutation - substitute one base for another Original: A T A C A C Mutant : T T A C A C
Frameshift Mutation - a base is either added or removed which causes a shift in the reading frame. Many genes affected - include insertion and deletion
Original: A T A C A C A A G C C A Mutant: A T T A C A C A A G C C A

45. Silent Mutation - a base is changed but the resulting amino acid is the same as in the non mutant DNA. No outward changes. Original: A A A C A G Mutant: A A G C A G
Nonsense Mutation - a codon is changed to a STOP codon Original: A T A C C C A A A Mutant: A T T C C C A A A

46. Frameshift mutation
A base is added or deleted and changes the reading frame
G A T    C A T    A A A 
G A T    A  C A   T A A  A

47. What happens when you have a nonfunctional protein?
Hemophilia
PKU
Cystic Fibrosis
Androgen Insensitivity - caused by a faulty receptor for androgens, individual is a chromosomal male but appears female  (pseudohermaphrodite)
Aside from having an ambiguous-looking external genitalia, true hermaphroditism in humans differs from pseudohermaphroditism in that the person's karyotype has both XX and XY chromosome pairs (47XXY, 46XX/46XY, 46XX/47XXY or 45X/XY mosaic) and having both testicular and ovarian tissue. One possible pathophysiologic explanation of this rare phenomenon is a parthenogenetic division of a haploid ovum into two haploid ova. Upon fertilization of the two ova by two sperm cells (one carrying an X and the other carrying a Y chromosome), the two fertilized ova are then fused together resulting in a person having dual genitalial, gonadal (ovotestes) and genetic sex.
Do you watch House?

48. In maize corn a colorless kernel results from the inability to create purple pigment.
If the transposon jumps to another location, the cells regain the ability to make the pigment, this creates a speckled pattern on the kernel

49. Transposons
Barbara McClintock studying maize corn found that controlling elements could move from one location to another on a chromosome
   --  Transposons or Jumping Genes
DNA and RNA transposons move around the genome. DNA transposons cut themselves out from their original location, and insert themselves somewhere else in the genome. RNA transposons make a copy of themselves that inserts into a new location, leaving the original transposon intact. (may have originated from viruses)

50. Transposons Define Transposons (there are 2+ types)
What effects do they have? Give an example.
What else did your learn from this article?

51. Cancer and Genetics
Growth of cancer often begins with the loss of the TUMOR SUPPRESSOR GENE 
ONCOGENES activate, cell division occurs uncontrollably
Breast Cancer Gene
BRCA1  (brak-uh)

52. Introns or Exons
Exons = parts of DNA that are transcribed and code for a protein
Introns = sections of DNA that are not transcribed, function unknown
sometimes once called this "JUNK DNA" - scientists now believe this is not accurate

53. What is Junk DNA? Use to be considered useless
Now, it is considered “noncoding”- don’t code for proteins, but can still be important to life functions, regulation, structures, features
Face is junk DNA