1. Identifying the Molecule of Inheritance
Predicting the Results of the Griffith Experiment and (Re)-Designing the Avery, MacLeod and McCarty Experiment

2. Objectives
Hypothesize outcomes for a given experiment given the data collected.
Design an experiment to conclude whether protein, DNA or RNA is the genetic material.
Explain why DNA makes a better genetic material than protein.

3. Griffith Experiment: Results

4. Griffith Experiment: What’s Going On?
What are TWO hypotheses that might explain the unexpected results of the experiment?
8000 BCE
Selective Breeding
400 BCE
Tiny particles from every part of the body mix from the “fluids” of each parent
1700s
Preformation
An organism contains all of its future descendants encased in miniature form
Homunculus
1800s
Heredity is a blending process

5. Bacterial Phenotypes S (smooth) strain R (rough) strain
The pneumococcus bacterium was a pathogenic bacterium that causes pneumonia in animals and humans.
A polysaccharide capsule surrounds some strains of S. pneumonia is essential for its pathogenicity
Layer of polysaccharides that lies outside the cell wall of some bacteria
It enhances the ability of bacteria to cause disease because it prevents phagocytosis of the bacterium by a white blood cell (macrophages)
The capsule can also exclude bacterial viruses, protect against desiccation, and prevent uptake of antibiotics
S (smooth) strain
R (rough) strain

6. Transformation Transformation: A change in phenotype.
Includes “transformation” in the context of cancer – a normal cell taking on a cancerous phenotype, including uncontrolled rate of growth, ability to metastasize (spread from primary site), etc.
In this case, “transformation” refers to non-pathogenic (non-infectious) bacteria taking on the properties / phenotype of pathogenic bacteria.
The R strain was transformed into the pathogenic S strain when mixed together, and pneumonia and death ensued in infected mice
This new “S” bacteria replicated like S strain bacteria, and possessed a capsule like the S strain
Some thing in the heat-killed bacteria could still transmit disease causing properties to the living “rough” bacteria
Transforming Principle
In 1928, when Frederick Griffith discovered the phenomenon of transformation in the non-pathogenic, “rough” bacteria. He proposed the concept of the “transforming principle.”
Some part of the dead S strain bacteria was able to transform the R strain to make it lethal
Some part of the dead S strain had survived the heating process and was taken up by the R strain bacteria
These S strain parts must contain the “genetic material” to build a new polysaccharide capsule

7. Discovery of “Nuclein”
In 1869, Freidrich Miescher was working with white blood cells from pus, derived from dirty bandages
He would then use techniques to isolate the nuclei from each cell on the bandage
Purified “nuclein” from isolated nuclei from every cell that he tested
This nuclein was known to be high in phosphorus (unlike proteins, carbohydrates and lipids)
The significance of the difference in this composition remained unknown in Miescher’s lifetime (it wasn’t until the discovery of the structure of DNA by Franklin, Watson and Crick that the relevance of PO4 in the backbone of DNA was realized).

8. Transforming Principle
Genes are on Chromosomes
T.H. Morgan discovered sex-linked traits, and defined the chromosomal theory of inhertiance, this being that genes lie on chromosomes.
BUT: Is it the proteins or the DNA of the chromosomes that are the genes?
Basic Requirements for the Genetic Material
Coding capacity
A large molecule
Enough structural variation to encode the huge variety of phenotypes
Self Replicable
Copying of the genetic material
Most people thought that protein was the genetic material. Why?
Mostly abundant, central molecules of life
Long enough
Versatile enough – 20 different amino acids
Thought that DNA couldn’t be the genetic material. Why?
Structure of DNA is too simple to encode the genetic materail – only 4 different nucleotides

9. Enzyme Toolbox
Protease: Any enzyme that digests proteins by the hydrolysis of peptide bonds that link amino acids together in a polypeptide chain.
DNase: Any enzyme that digests DNA by the hydrolysis of phosphodiester bonds in the DNA backbone.
RNase: Any enzyme that degrades RNA into smaller components.

10. Objectives
Hypothesize outcomes for a given experiment given the data collected.
Design an experiment to conclude whether protein, DNA or RNA is the genetic material.
Explain why DNA makes a better genetic material than protein.

11. Avery, MacLeod and McCarty Conclusions

12. Avery, MacLeod and McCarty Conclusions