1. MOLECULAR BASIS OF INHERITANCE 2. ONCE UPON A TIME…THE WAY THAT EVERY TRULY GOOD STORY BEGINS. a. In 1953, James Watson and Francis Crick won a very competitive race to discover the molecular structure of DNA. 3. LINUS PAULING 4. Deoxyribonucleic Acid a. The arrangement of covalent bonds in a nucleic acid polymer was well established, but not the 3 dimensional structures. 5. Rosalind Franklin. Where is poor Maurice? a. Rosalind Franklin and Maurice Wilkins were experts in the technique of X-ray diffraction. b. DNA X-ray diffraction is a technique in which DNA, or any other molecule being researched, is crystallized, bombarded with x-ray, creating pictures of diffraction (deflection) patterns –patterns of how x-ray bounced off of the DNA. c. Crystallographers use mathematical equations to translate such patterns of spots into information about the three dimensional shape of molecules. 6. DNA: “A Rope Ladder” a. Watson and Crick spent hours arguing over everything they had read about DNA. They did not do experiments on DNA. They built models. 7. PURINES AND PYRIMIDINES a. The nitrogen bases that are part of the nucleotides that make up DNA are purines or pyrimidines: b. Adenine and Guanine are both purines, c. Thymine and Cytosine are both pyrimidines. 8. Purine and Pyrimidine: Width consistent with x-ray data a. The solution based on the data became obvious – to pair a pyrimidine with a purine. 9. BASE PAIRING and DNA a. Adenine always pairs with thymine. b. Guanine always pairs with cytosine. c. This represents a purine with a pyrimidine. d. Thank you Erwin Chargaff. 10. PAULING DISCOVERED THE ALPHA HELIX OF PROTEINS 11. ROSALIND FRANKLIN DIED AT 37? YEARS OF AGE 12. HOW DID IT ALL BEGIN? a. It wasn’t just Watson and Crick. Like all scientific discovery, it is built on the hard work of everyone who came before. b. Hundreds of scientists contributed to the discovery of DNA that is credited to a few Nobel Prize winners. c. By the 1800’s, scientists knew that heritable information existed in discreet units called “genes”. page 1 of 5 molecular basis of inheritance Beavers 13. FREDRICK GRIFFITH’S EXPERIMENTS a. In the 1920’s, a British researcher named Frederick Griffith was attempting to produce a vaccine to prevent bacterial pneumonia. b. It was not known then how difficult it was to produce this type of vaccine. c. Griffith was trying to make a vaccine using two strains of the Streptococcus pnemoniae bacterium. 14. Griffith grew bacterial colonies of bacteria in the lab – in Petri dishes. 15. TRANSFORMATION: A method of acquiring new genes, whereby DNA from one bacterium (normally released after the death of the bacterium) becomes incorporated into the DNA of another, living bacterium. a. Griffith’s use of heat to inactivate the S cells hinted that protein might not be the genetic material. 16. DNA IDENTIFIED a. AVERY PICTURE TAPED UP. b. In 1944 - Avery, MacLeod and McCarty of Rockefeller University purified various chemicals from the heat-killed S cells and found only DNA could transform the R cells. c. While experimenting with the R and S cells, Avery added protein digesting enzymes to the S cells, and they still transformed the R cells, so protein could not be the hereditary material. d. He also added DNA digesting enzymes to R cells mixed with S cell fluid, and R cells were not transformed. e. DNA WAS A GOOD CANDIDATE. f. Most scientists were not convinced they were correct – they could not believe that the genes of bacteria would be similar in composition and function to those of more complex organisms. g. TOO LITTLE WAS KNOWN ABOUT DNA. 17. HOW DOES DNA PASS ON HEREDITARY INFORMATION? a. All dogs share similarities because their genes are nearly identical. b. The amazing varieties in body size, fur length, and color results from tiny differences in their genes. c. LET US INVESTIGATE DNA. START BIG picture: 18. CHROMOSOMES: A single DNA double-helix together with proteins that help to organize the DNA. a. GENES: A unit of heredity that encodes the information needed to specify the amino acid sequence of proteins and hence particular traits; a functional segment of DNA located at a particular place on a chromosome. 19. STRUCTURE OF DNA a. The DNA of every organism on earth is composed of four small subunits called nucleotides. b. Nucleotides: a subunit of which nucleic acids are composed; a phosphate group bonded to a sugar (deoxyribose in DNA), which is in turn bonded to a nitrogen-containing base. Nucleotides are linked together, forming a strand of nucleic acid as follows: bonds between the phosphate of one nucleotide link to the sugar of the next nucleotide. 20. NITROGEN CONTAINING BASES: Pyrimidines page 2 of 5 molecular basis of inheritance Beavers i. Two of the nitrogen containing bases of DNA are pyrimidines – nitrogen bases that have one ring. 1. These are: 2. Thymine or “T” 3. Cytosine or “C” 21. The other two nitrogen-containing bases of DNA are purines – they have two rings. 1. Adenine: “A” 2. Guanine: “G” 3. These are the “letters” that make up the genetic code. 22. STRUCTURE OF DNA a. The double-helix of DNA is made up of two “strands” of separate DNA polymers of linked nucleotides. The phosphate group of one nucleotide bonds to the sugar of the next nucleotide. This creates the “sugar-phosphate backbone”. 23. STRUCTURE OF DNA a. All nucleotides within a single DNA strand are oriented in the same direction. This causes the two ends of a DNA strand to differ; one end has a free or unbonded sugar, the other a free or unbonded phosphate. 24. STRUCTURE OF DNA a. The individual strands are held together by hydrogen bonds that form between the protruding bases. This creates the ‘ladder look’. The ladder is not straight; it is twisted, forming the double helix. 25. STRUCTURE OF DNA a. The two strands are oriented in OPPOSITE DIRECTIONS. b. Imagine a freeway during a traffic jam, with cars going in both directions. 26. STRUCTURE OF DNA a. Complementary base pairs: In nucleic acids, bases that pair by hydrogen bonding. In DNA, adenine is complementary to thymine (2 hydrogen bonds) and guanine is complementary to cytosine (3 hydrogen bonds). 27. A – T C-G a. How can such simplicity create such diversity? b. The four types of bases can be arranged in any linear order to encode genetic information. 28. DNA STRUCTURE SUMMARY a. DNA IS COMPOSED OF SUBUNITS CALLED NUCLEOTIDES. b. NUCLEOTIDES ARE LINKED IN LONG STRANDS. c. EACH NUCLEOTIDE HAS A PHOSPHATE GROUP, A FIVE-CARBON SUGAR CALLED DEOXYRIBOSE, AND A NITROGEN- CONTAINING BASE. d. FOUR NITROGEN CONTAINING BASES OCCUR IN DNA: A,T,C,G. 29. DNA STRUCTURE SUMMARY a. TWO NUCLEOTIDE STRANDS WIND ABOUT ONE ANOTHER TO FORM A DOUBLE HELIX. page 3 of 5 molecular basis of inheritance Beavers b. THE SUGAR OF ONE NUCLEOTIDE IS LINKED TO THE PHOSPHATE OF THE NEXT TO CREATE THE “SUGAR-PHOSPHATE BACKBONE”. c. THE NUCLEOTIDES OF EACH STRAND ARE HELD TOGETHER BY HYDROGEN BONDS. d. ONLY “A” CAN BOND WITH “T”, ONLY “C” CAN BOND WITH “G”. 30. CELL THEORY: “All cells come from [pre-existing] cells”. a. All of the trillions of cells in your body are the “offspring” or daughter cells of other cells starting with the egg fertilized by sperm. b. Every cell contains identical genetic information – the same as in the fertilized egg. 31. DNA REPLICATION a. Cell division occurs by a process called mitosis…but how does DNA replicate itself first?? b. Every daughter cells receives a nearly perfect (hopefully!!!) copy of the parent cell’s genetic information. c. The synthesis of two exact copies must go through a process called DNA replication. 32. DNA REPLICATION SIMPLY STATED a. ENZYMES PULL DNA APART b. ENZYMES MOVE ALONG EACH STRAND MATCHING ‘FREE’ BASES TO CREATE A NEW STRAND. c. EACH NEW STRAND CONTAINS ONE PARENTAL STRAND AND ONE NEW STRAND. d. THIS IS SEMI-CONSERVATIVE REPLICATION. 33. DNA REPLICATION a. DNA helicases – the enzymes that “unwinds” the DNA double-helix strands. b. This allows the bases of each strand to bond with “free nucleotides” accomplished by DNA POLYMERASE. 34. REPLICATION IS SEMICONSERVATIVE a. Each new strand of DNA conserves ONE copy of the parental DNA strand. b. This is referred to as semiconservative replication. c. Now the cell can prepare for mitosis. 35. WHAT WOULD THE NEW STRAND OF THIS PARENTAL STRAND BE? 1. A 2. T 3. C 4. A 5. A 6. G 7. G 36. WERNER SYNDROME Premature Aging a. What happens when there are problems with DNA replication? b. More common in people of Japanese ancestry, a mutation that interferes with an enzyme involved in accurate DNA replication. page 4 of 5 molecular basis of inheritance Beavers c. Greater than 400 cases in the world have been identified. It is autosomal recessive and has been mapped to chromosome 8p12, possibly a mutation in DNA Helicases (unwinding DNA properly). d. This woman is only 48 years old. e. Most people with Werner syndrome die by 50 due to aging complications. 37. DNA ERRORS a. DNA REPLICATES AT APPROXIMATELY 700 NUCLEOTIDES PER SECOND. b. DNA POLYMERASE MATCHES BASES INCORRECTLY 1/10,000 BASE PAIRS. c. DNA PROOF-READING ENZYMES CORRECT MANY ERRORS! d. THIS SAFETY NET MEANS ONLY 1 IN EVERY BILLION BASE PAIR IS INCORRECT page 5 of 5 molecular basis of inheritance Beavers