2. The History of DNA How we know what we know

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. Chromosomes related to phenotype T.H. Morgan –working with Drosophila fruit flies –associated phenotype with specific chromosome 1908 | 1933

5. Morgan’s conclusion Genes are on chromosomes –but is it the protein or the DNA of the chromosomes that are the genes? initially proteins were thought to be genetic material… Why? 1908 | 1933 What ’ s so impressive about proteins?!

6. DNA history http://media.hhmi.org/biointeractive/films/D ouble_Helix.htmlhttp://media.hhmi.org/biointeractive/films/D ouble_Helix.html

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

8. 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

9. Oswald AveryMaclyn McCartyColin MacLeod Avery, McCarty & MacLeod 1944 | ??!! Conclusion DNA is the transforming principle

10. Confirmation of DNA Hershey & Chase –classic “blender” experiment –worked with bacteriophage viruses that infect bacteria –grew phage viruses in 2 media, radioactively labeled with either P 32 (P is in DNA) S 35 (S is in Protein) –infected bacteria with labeled phages 1952 | 1969 Hershey Why use S ulfur vs. P hosphorus?

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

12. Chargaff Regarding A, T, C, and G –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% A + G = T + C –That is: amount of purines = amount of pyrimidines 1947 That ’ s interesting! What do you notice? Rules A = T C = G

13. Chargoff’s rules http://www.hhmi.org/biointeractive/chargaff s-ratiohttp://www.hhmi.org/biointeractive/chargaff s-ratio

14. Structure of DNA Watson & Crick –The Double Helix other leading scientists working on question: –Rosalind Franklin –Maurice Wilkins –Linus Pauling 1953 | 1962 Franklin WilkinsPauling

15. The Double Helix - 1953

16. Rosalind Franklin (1920-1958)

17. Watson and Crick Determined the DOUBLE HELIX model Two strands of nucleotides, joined at the bases A with T and G with C (a purine with a pyrimidine) (Chargoff’s Rules) Complementary Base Pairs: A-T with 2 hydrogen bonds G-C with 3 H bonds

18. The Double Helix Why can’t two purines or two pyrimidines pair up?

19. Summary of DNA Structure DNA has two polymers of nucleotides which are Anti-parallel (not Watson/Crick) It resembles a ladder where the Sugar-phosphates are the sides and The base pairs are the rungs It then twists into a Double Helix

20. Anti-Parallel One polymer goes from #5C to #3C and the other goes from #3C to #5C

21. DNA structure http://www.hhmi.org/biointeractive/chemic al-structure-dnahttp://www.hhmi.org/biointeractive/chemic al-structure-dna http://www.hhmi.org/biointeractive/coding- sequences-dnahttp://www.hhmi.org/biointeractive/coding- sequences-dna

22. The Genetic Code What makes one section of DNA different from another? The sequence of bases The Genetic code is the sequence of bases in the DNA

23. But how is DNA copied? Replication of DNA –base pairing suggests that it will allow each side to serve as a template for a new strand “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

24. Functions of DNA 1. Replication – Occurs before Mitosis and meiosis only Produces an exact copy of DNA 2. Transcription – DNA makes mRNA in order to make protein (DNA---RNA----Protein) This is the function of individual genes

25. proteinRNA The “Central Dogma” DNA Flow of genetic information in a cell Replication transcriptiontranslation