1. Chapter 12 Molecular Genetics
12.1 DNA: The Genetic Material

2. Discovery of the Genetic Material
Chromosomes are about 50% nucleic acid and 50% protein, which is the genetic material?
Most scientists thought that protein was the genetic material because protein is more complex
Griffith performed the first major experiment that led to the discovery of DNA as the genetic material

3. Discovery of the Genetic Material

4. Discovery of the Genetic Material
Significance of Griffith’s work (1928)
One strain of bacteria transformed into another strain
Did not identify what the transforming substance was

5. Discovery of the Genetic Material
1944 Oswald Avery identified that DNA was the transforming substance in Griffith’s experiments
Most leading scientists did not believe him

6. Discovery of the Genetic Material
1952 Hershey and Chase used radioactively labeled DNA and radioactively labeled protein and proved that DNA is the genetic material

7. DNA Structure DNA is made of subunits called nucleotides
Three parts to a DNA nucleotide
Sugar
Phosphate
Nitrogen Base
NUCLEOTIDE

8. DNA Structure Four Different Nitrogen Bases Purine (two rings)
Adenine
Guanine
Pyrimidine (one ring)
Cytosine
Thymine
Uracil (not found in DNA)

9. DNA Structure Chargaff’s Rule
Chargaff determined in 1950 that the amount of adenine equals the amount of thymine and the amount of guanine equals the amount of cytosine
Chargaff’s Rule: A=T and C=G

10. DNA Structure: X Ray Diffraction
Rosalind Franklin’s (1951) famous photo of X ray diffraction of DNA

11. DNA Structure: Double Helix
In 1953 Watson and Crick astounded the scientific community with their announcement of DNA’s structure

12. DNA Structure: Double Helix
Watson and Crick, using Franklin’s photo, determined that DNA is a double helix with:
Outside strands of alternating sugar and phosphate
C bonds with G with three hydrogen bonds
A bonds with T with two hydrogen bonds

13. DNA Structure: Double Helix
DNA called a twisted ladder
Sugar is deoxyribose in the upright rails of the “ladder” alternating with phosphate (spacers)
Rungs of the “ladder” have a purine base H-bonded to a pyrimidine base

14. DNA Structure: Double Helix
DNA strands are antiparellel (one strand right side up and other stand upside down)
Stands named by their Carbon orientation, C-5 (5’) or C-3 (3’)

15. Chromosome Structure
An average sized chromosome would be 5 cm long if the DNA were stretched out
DNA is packaged to be condensed in the cell’s nucleus

16. Chapter 12 Molecular Genetics
12.2 Replication of DNA

17. Semiconservative Replication
DNA original stand untwists
New base pairs bond to open existing stands following base paring rules (A=T, C=G)
New strands twist; each new helix is half new half original

18. Enzymes Control DNA Replication Enzymes Control DNA Replication
Untwisting by DNA helicase
Strands kept apart by single-stranded binding proteins
Add “starter” RNA segment by RNA primase
Add new nucleotides by DNA polymerase
This is only the highlights; there are many other enzymes involved

19. DNA Replication
Because DNA is antiparallel and new nucleotides can only be added to the 3’ end, each strand replicates slightly differently

20. DNA Replication
Leading strand replicates by continuous addition of nucleotides to the 3’ end
Lagging strand replicates by producing short DNA sections called Okazaki fragments
Enzyme ligase “glues” the fragments together

21. Comparing DNA Replication in Eukaryotes and Prokaryotes
Eukaryotes have multiple areas of DNA replication along one chromosome
Prokaryotes have one circular chromosome and have only one origin of replication

22. Chapter 12 Molecular Genetics
12.3 DNA, RNA, and Protein

23. Central Dogma
How does the information in DNA, located in the nucleus, allow for the production proteins in the cytoplasm?
RNA is another form of nucleic acid that relays the information.

24. RNA versus DNA RNA Single helix Ribose sugar
Bases: adenine, guanine, cytosine, and uracil
Several types of RNA
DNA
Double helix
Deoxyribose sugar
Bases: adenine, guanine, cytosine, and thymine
One type of DNA

25. RNA versus DNA

26. Types of RNA
Messenger RNA (mRNA): long strands (hundreds of nucleotides) that are formed complementary to DNA; leave the nucleus to carry information to the cytoplasm
Transfer RNA (tRNA): short ( nucleotides) T-shaped RNA that transport amino acids
Ribosomal RNA (rRNA): along with protein make up the ribosomes
There are several other types of RNA also; each with a specific function.

27. Types of RNA

28. DNA to RNA to Protein Two step process: transcription and translation
Transcription (rewrite): RNA is made from DNA; occurs in the nucleus
Translation (change language): protein is made from RNA code; occurs in the cytoplasm at the ribosome

29. Transcription
A section DNA (ave. size 8000 nucleotides) in the nucleus untwists and unzips.
RNA nucleotides, following base pairing rules, bond on the leading strand of DNA
Like DNA replication controlled by many enzymes
Occurs in the nucleus

30. RNA Processing RNA when it is transcribed must be processed
GTP cap is added to 5’ end to protect and give attach signal to ribosome
Introns (intervening sequences) are cut out
Exons (expressed sequences) are put together
Poly-A tail ( A nucleotides) added to 3’ end to protect and “get out of nucleus” signal

31. Translation: Making Protein
Starts when mRNA, tRNA carrying amino acids, and small and large ribosomal subunits come together
Concludes when a polypeptide chain in produced

32. The Code
There are 20 amino acids, each is coded for by a sequence of 3 nucleotides called a codon.
Discovered during the 1960’s.

33. The Code mRNA Genetic Code mRNA has the codon
tRNA has the anticodon (complementary to the codon)
Example: mRNA codon AUG would code for the amino acid methionine which is also the start codon
Redundancy exists: more that one codon per amino acid (UAU and UAC codes for tyrosine)
Ambiguity does not exist: UAU only codes for tyrosine not any other amino acid.

35. Translation All the players come together
First tRNA with anticodon UAC carrying methionine bonds with mRNA codon AUG at the P-site of the ribosome
Second tRNA with anticodon carrying another amino acid bonds with complementary mRNA codon at A-site of ribosome
Polypeptide bond forms between two amino acids
Ribosome moves down the mRNA so that the first tRNA is now in E-site of ribosome (and is released)
A-site is now empty to attach the third tRNA carrying the third amino acid
Steps 4-7 repeated until mRNA codon for stop is signaled, then polypeptide chain released

36. One Gene-One Enzyme
The Beadle and Tatum experiment showed that one gene codes for one enzyme. We now know that one gene codes for one polypeptide.

38. Chapter 12 Molecular Genetics
12.4 Gene Regulation and Mutation

39. Prokaryote Gene Regulation
Ability of an organism to control which genes are transcribed in response to the environment
An operon is a section of DNA that contains the genes for the proteins needed for a specific metabolic pathway.

40. Lac Operon

41. Try Operon
What would an off Try operon look like?

42. Eukaryote Gene Regulation
Controlling transcription: transcription factors ensure that a gene is used at the right time and that proteins are made in the right amounts
Promoters: stabilize binding of RNA polymerase
Regulatory proteins: control rate of transcription
The complex structure of eukaryotic DNA also regulates transcription.

43. Eukaryote Gene Regulation
Hox genes are responsible for the general body pattern of most animals.
Hox genes code for transcription factors that are active in zones of the embryo that are in the same order as the genes on the chromosome

44. Eukaryote Gene Regulation
RNA interference can stop the mRNA from translating its message.

45. Mutations Mistakes occur in copying the DNA during replication.
Mechanisms exist for correcting these mistakes
If the mistakes are permanent then a mutation occurs
If a mutation in the DNA occurs, then the protein that is made from this DNA instruction can be absent or nonfunctional.

46. Mutations

47. Mutations

48. Types of Mutations

49. Chromosomal Mutations
Pieces of chromosomes get deleted, duplicated, inverted, inserted or translocated
Visible on karyotype

50. Chromosomal Mutations
Fragile X chromosome is due to about 30 extra repeated CGG codons near the tip of the X chromosome
Results in many mental and behavioral symptoms

51. Protein Folding and Stability
Incorrect amino acid sequences can lead to changes in the shape and thus the function of proteins

52. Causes of Mutations Mutagens are agents that cause mutations
Spontaneous: no known cause; wrong nucleotide
Occurs 1/100,000 base pairs
Remains unfixed less than one in one billion

53. Causes of Mutations
Chemicals like asbestos, benzene, formaldehyde, multiple agents in cigarette smoke, and many others
Affect DNA by changing chemical nature of the bases
May resemble nucleotides and bond in place of the DNA nucleotides preventing DNA replication

54. Causes of Mutations
Radiation: high energy rays like X rays and gamma rays; form free radicals (charged escaped electrons) that damages DNA
UV radiation can cause adjacent thymines to bind with each other instead of complementary nucleotides causing a “kink” in the DNA molecule which prevents replication

55. Body Cell versus Sex Cell Mutation
Molecular Genetics
Body Cell versus Sex Cell Mutation
Somatic cell mutations are not passed on to the next generation.
Mutations that occur in sex cells are passed on to the organism’s offspring and will be present in every cell of the offspring.