1. The Genetic Code The word genetic refers to heredity. A code is a set of symbols or signals used to pass on information. The genetic code is the way in which cells store information that is passed from one generation to the next generation.

2. The Search for the Genetic Code Frederick Griffith: He studied bacteria that caused pneumonia in mice. In 1928 he did the following experiment.

3. Transformation Of Bacteria Two Strains Of Streptococcus Capsules Smooth Strain (Virulent) Rough Strain (Harmless)

4. Experimental Transformation Of Bacteria The Griffith Experiment - Control + Control - Control OUCH!

5. The Search for the Genetic Code

6. Results from #4 show that the heat-killed strain had passed to the live harmless strain its disease-causing ability. That is, one form of bacteria was transformed into another form. Griffith called this process transformation. He hypothesized that a factor was transferred from the heat killed cells into the live cells

7. The Search for the Genetic Code Oswald Avery and others: In 1944 they repeated Griffith’s experiment to see which molecules were responsible for the transformation. From the heat-killed bacteria they made an extract or juice. Individually they treated the extract with enzymes that destroy lipids, proteins, carbohydrates, and RNA.

8. The Search for the Genetic Code The results were that transformation still occurred and so none of these molecules were the transferring agent. They repeated the experiment with enzymes that break down DNA (deoxyribonucleic acid). The results were that transformation did not take place.

9. NoNuclease YesProtease YesLippase Transformation?Enzyme YesSaccharase

10. The Search for the Genetic Code Conclusion: DNA is the transforming material and is the molecule that stores and transmits the genetic code from one generation of an organism to the next.

11. SEARCH FOR THE GENETIC CODE CONTINUES After the Oswald Avery experiment some scientists still remained skeptical that DNA was the genetic material. In 1952 the following experiment was done by Alfred Hershey and Martha Chase.

12. The Hershey-Chase Experiment They used bacteriophages which are viruses that infect bacteria (e.g., T2 phage). They are composed of a DNA core and a protein coat. They infect bacteria by attaching to the surface and injecting material.

13. The Hershey-Chase Experiment The injected material is used to make many copies of the virus. Viral copies are produced until they cause the bacteria to burst, releasing the virus. Because the injected material is used to make copies, it must be the genetic code. Important question: What is being injected from the virus, the protein coat or DNA core?

14. The Hershey-Chase Experiment They labeled the protein coat of the virus with radioactive sulfur-35. They labeled the DNA core of the virus with radioactive phosphorus-32. They mixed the labeled viruses with the bacteria, waited for injection, & then separated the parts using a blender and centrifuge.

15. The Hershey-Chase Experiment Hershey and Chase took advantage of the fact that T2 phage is made of only two things: Protein and DNA H OH P O HO O NH 2 Nucleotides contain phosphorous, thus DNA contains phosphorous, but not sulfur. H OH O H2NH2NCC CH 2 SH H OH O H2NH2NC CH 3 C CH 2 S Some amino acids contain sulfur, thus proteins contain sulfur, but not phosphorous. CysteineMethionine

16. Using S 35 Bacteria grown in normal non- radioactive media T2 grown in S 35 containing media incorporate S 35 into their proteins Blending causes phage protein coat to fall off T2 attach to bacteria and inject genetic material Is protein the genetic material? When centrifuged, phage protein coats remain in the supernatant while bacteria form a pellet The supernatant is radioactive, but the pellet is not. Did protein enter the bacteria?

17. Using P 32 Bacteria grown in normal non- radioactive media T2 grown in P 32 containing media incorporate P 32 into their DNA Blending causes phage protein coat to fall off T2 attach to bacteria and inject genetic material Is DNA the genetic material? When centrifuged, phage protein coats remain in the supernatant while bacteria form a pellet The pellet is radioactive, but the supernatant is not. Did DNA enter the bacteria?

18. The Hershey-Chase Experiment

19. Conclusion: The Hershey-Chase experiment showed definitively that DNA is the molecule that carries the genetic code.

20. AN IMPORTANT QUESTION REMAINED: WHAT IS THE STRUCTURE OF DNA? In the early 1950’s Rosalind Franklin & Maurice Wilkins took x-ray pictures of the DNA molecule. These x-ray pictures provided important clues about the structure of DNA. For example, the fibers that make up DNA are twisted and the molecules in the fibers are spaced out in regular intervals.

21. AN IMPORTANT QUESTION REMAINED: WHAT IS THE STRUCTURE OF DNA? Another important piece of information on the structure of DNA was provided by Erwin Chargaff. He observed that in any sample of DNA, the number of: Adenine molecules (A) = (T) Thymine molecules Cytosine molecules (C) = (G) Guanine molecules