1 Lecture no. 4 DNA: The Genetic Material

2 Terminologies (see Early experiments that led to the discover of DNA as the genetic material. Lecture no. 4

3 Characteristics of “The Genetic Material”: Must be a stable form containing information about cell form and function. Must replicate accurately. Must be able to change/evolve. Until 1944 it was not known which component of chromosomes was the genetic material. Until 1953 it was not known how DNA could encode genetic information. 3 Lecture no. 4

Early Studies Beginning with the earliest observations concerning heredity, genetic material was assumed to exist. Until the 1940s proteins were considered by geneticists to be the best candidates:  Very abundant in cells and did nifty things.  Nucleic acids were similar, and just a couple of nucleotides connected to each other… Lecture no. 4

5 Phoebus Levene proposed a tetranucleotide structure !! for DNA He though that a DNA molecule contained only four units, each unit contain phosphate-sugar-base -in order- linked together in a repeated manner, i.e. a tetranucleotide. Furthermore, he considered such a simple sequence could not allow DNA any role in coding for anything. This was later to be proved wrong by Chargaff. Lecture no. 4

So… It was widely thought that DNA was organized into repeating "tetranucleotides" in a way that could not carry genetic information. Proteins, on the other hand, had 20 different amino acids and could have lots of variation. Most geneticists focused on “transmission genetics” and passively accepted proteins as being the likely genetic material Lecture no. 4

7 Toward The Real Conclusion Griffith’s Transformation Experiment Tobacco Mosaic Virus (TMV) Experiment Avery’s Transformation Experiment Hershey-Chase Bacteriophage Experiment Lecture no. 4

First Real Break- First Real Break- Frederick Griffith’s Transformation Experiment. 8 Griffith concluded that the type II-R had been "transformed" into the lethal III-S strain by a "transforming factor“. Griffith hypothesized that the transforming factor was a “IIIS” protein. Griffith concluded that the type II-R had been "transformed" into the lethal III-S strain by a "transforming factor“. Griffith hypothesized that the transforming factor was a “IIIS” protein Lecture no. 4

Continue… Continue… Avery’s Transformation Experiment 9 When DNA was destroyed, the transforming activity was lost, but when DNA was left intact, the transforming activity survived When DNA was destroyed, the transforming activity was lost, but when DNA was left intact, the transforming activity survived 1944 Lecture no. 4

10 When DNA was destroyed, the transforming activity was lost, but when DNA was left intact, the transforming activity survived. Continue… Continue… Avery’s Transformation Experiment 1944 Lecture no. 4

Continue… Continue… Hershey-Chase Bacteriophage Experiment Because DNA and not protein entered the cell, then DNA must be the heritable material (i.e., responsible for the function and reproduction of phage). A.H. received Nobel Prize in 1969 for this & other work Because DNA and not protein entered the cell, then DNA must be the heritable material (i.e., responsible for the function and reproduction of phage). A.H. received Nobel Prize in 1969 for this & other work 1953 Lecture no. 4

- Gierer & Schramm (TMV) Experiment Gierer & Schramm 1956/Fraenkel-Conrat & Singer 1957 Used 2 viral strains to demonstrate RNA is the genetic material of TMV. Gierer & Schramm 1956/Fraenkel-Conrat & Singer 1957 Used 2 viral strains to demonstrate RNA is the genetic material of TMV. RNA as Genetic Material 1956 Lecture no. 4

In conclusion 13 DNA (not RNA) is transforming agent DNA (not protein) is the genetic material RNA (not protein) is genetic material of some viruses Lecture no. 4

14 Chargaff’s Rules , evidence for DNA as genetic material. Digested many DNAs and subjected products to chromatographic separation Results: A = T, C = G A + G = C + T (purine = pyrimidine) A + T does not equal C + G Members of a species similar but different species vary in AT/CG ratio Lecture no. 4

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