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AP Biology

AP Biology. Lecture #30 History of the Molecular Basis for Inheritance. The Molecular Basis of Inheritance. Scientific History. The march to understanding that DNA is the genetic material T.H. Morgan (1908) Frederick Griffith (1928) Avery, McCarty & MacLeod (1944) Erwin Chargaff (1947)

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AP Biology

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  1. AP Biology Lecture #30 History of the Molecular Basis for Inheritance

  2. The Molecular Basis of Inheritance

  3. Scientific History • The march to understanding that DNA is the genetic material • T.H. Morgan (1908) • Frederick Griffith (1928) • Avery, McCarty & MacLeod (1944) • Erwin Chargaff (1947) • Hershey & Chase (1952) • Watson & Crick (1953) • Meselson & Stahl (1958)

  4. The “Transforming Principle” 1928 • Frederick Griffith • Streptococcus pneumonia bacteria • was working to find cure for pneumonia • harmless live bacteria (“rough”) mixed with heat-killed pathogenic bacteria (“smooth”) causes fatal disease in mice • a substance passed from dead bacteria to live bacteria to change their phenotype • “Transforming Principle”

  5. The “Transforming Principle” mix heat-killed pathogenic & non-pathogenic bacteria live pathogenic strain of bacteria live non-pathogenic strain of bacteria heat-killed pathogenicbacteria A. B. D. C. mice die mice live mice live mice die Transformation=change in phenotype something in heat-killed bacteria could still transmit disease-causing properties

  6. DNA is the “Transforming Principle” 1944 • Avery, McCarty & MacLeod • purified both DNA & proteins separately from Streptococcus pneumonia bacteria • which will transform non-pathogenic bacteria? • injected protein into bacteria • no effect • injected DNA into bacteria • transformed harmless bacteria into virulent bacteria mice die What’s the conclusion?

  7. Avery Experiment

  8. Avery, McCarty & MacLeod 1944 | ??!! • Conclusion • first experimental evidence that DNA was the genetic material Oswald Avery Maclyn McCarty Colin MacLeod

  9. Confirmation of DNA 1952 | 1969 Hershey • Hershey & Chase • classic “blender” experiment • worked with bacteriophage • viruses that infect bacteria • grew phage viruses in 2 media, radioactively labeled with either • 35S in their proteins • 32P in their DNA • infected bacteria with labeled phages Why useSulfurvs.Phosphorus?

  10. Hershey & Chase Protein coat labeled with 35S DNA labeled with 32P T2 bacteriophages are labeled with radioactive isotopes S vs. P bacteriophages infect bacterial cells bacterial cells are agitated to remove viral protein coats Which radioactive marker is found inside the cell? Which molecule carries viral genetic info? 32P radioactivity foundin the bacterial cells 35S radioactivity found in the medium

  11. Blender experiment • Radioactive phage & bacteria in blender • 35S phage • radioactive proteins stayed in supernatant • therefore viral protein did NOT enter bacteria • 32P phage • radioactive DNA stayed in pellet • therefore viral DNA did enter bacteria • Confirmed DNA is “transforming factor” Taaa-Daaa!

  12. Hershey & Chase 1952 | 1969 Hershey Martha Chase Alfred Hershey

  13. Chargaff 1947 • DNA composition: “Chargaff’s rules” • varies from species to species • all 4 bases not in equal quantity • bases present in characteristic ratio • humans: A = 30.9% T = 29.4% G = 19.9% C = 19.8% RulesA = T C = G That’s interesting!What do you notice?

  14. Structure of DNA 1953 | 1962 • Watson & Crick • Credited with double helix model of DNA • other leading scientists working on question: • Rosalind Franklin - crystallography • Maurice Wilkins - crystallography • Linus Pauling – alpha helix in proteins Wilkins Pauling Franklin

  15. 1953 article in Nature Watson and Crick Watson Crick

  16. Rosalind Franklin (1920-1958)

  17. Double helix structure of DNA “It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material.” Watson & Crick

  18. Directionality of DNA nucleotide • You need to number the carbons! • it matters! PO4 N base 5 CH2 This will beIMPORTANT!! O 1 4 ribose 3 2 OH

  19. The DNA backbone 5 PO4 • Putting the DNA backbone together • refer to the 3 and 5 ends of the DNA • the last trailing carbon base CH2 5 O 4 1 C 3 2 O P –O O Sounds trivial, but…this will beIMPORTANT!! O base CH2 5 O 4 1 2 3 OH 3

  20. Anti-parallel strands • Nucleotides in DNA backbone are bonded from phosphate to sugar between 3 & 5 carbons • DNA molecule has “direction” • complementary strand runs in opposite direction 5 3 3 5

  21. hydrogen bonds covalent phosphodiester bonds Bonding in DNA 5 3 3 5 ….strong or weak bonds? How do the bonds fit the mechanism for copying DNA?

  22. Base pairing in DNA • Purines • adenine (A) • guanine (G) • Pyrimidines • thymine (T) • cytosine (C) • Pairing • A : T • 2 bonds • C : G • 3 bonds

  23. Characteristics of Double Helix 3’ 5’ 1 2 3 4 5 6 7 8 9 10 5’ 3’ 36 Å Large groove Small groove 1 Twist = 10.5 bp

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