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Discovery of Nucleic Acids
Friedrich Miescher (Swiss physician/biologist) 1844-1995
He isolated the genetic material from white blood cell nuclei. He noted it had an acidic nature and called it nuclein. -
Discovery of DNA components
Phoebus Levene (Lithuanian-American Biochemist) 1869-1940.
He determined the components of DNA:
- Adenine, guanine, thymine, cytosine, deoxyribose phosphate.
- Defined phosphate-sugar-base units called nucleotides. -
Levene's Tetranucleotide
Levene proposed that there were four nucleotides per molecule.
Said DNA could not store the genetic code because it was chemically far too simple.
This was his proposal for the DNA structure. -
Frederick Griffith and his Transformation Experiment
Friedrick Griffith (1879-1941) British bacteriologist.
He studied the epidemiology and pathology of 2 strains of Streptococcus pneumoniae.
In January 1928 he reported the first widely accepted demonstrations of bacterial transformation.
Griffith used two strains of Streptococcus:
Type S: virulent (deadly)
Type R: non-virulent (harmless)
He observed bacterial transformation but did not understand the mechanism. -
Experiment Friedrick Griffith
The “Griffith's Experiment,” conducted in 1928 by English bacteriologist Frederick Griffith described the conversion of a non-pathogenic pneumococcal bacteria to a virulent strain. In this experiment, Griffith mixed the living non-virulent bacteria with a heat inactivated virulent form. -
Avery, Macleod and McCarty
Determined the cause of the transformation in Griffith's Experiment.
They took live R and heat-treated S and mixed it with one of two enzymes:
- a protease (destroys protein)
- a DNAse (destroys DNA)
Finally, they concluded that DNA (not proteins) can transform the properties of cells, clarifying the chemical nature of genes. Avery, MacLeod and McCarty identified DNA as the "transforming principle" while studying Streptococcus pneumonia, bacteria that can cause pneumonia. -
Journal of Experimental Medicine
Published in the Journal of Experimental Medicine
February 1944
Studies on the Chemical Nature of the Substance Inducing Transformation of Pneumococcal Types: Induction of Transformation by a Deoxyribonucleic Acid Fraction Isolated from Pneumococcus Type III
DNA, not protein was responsible for the bacterial transformation Griffith observed! -
Double Helix
In 1951, Watson and Crick wrote a paper in which they described DNA as a double helix with sugars and phosphates at the center and the nucleobases facing the outside
This model was quickly shown to be incorrect, and in fact it made no chemical sense. -
Counting Nucleobases
Erwin Chargoff Austrian biochemist (1905-2002)
He used paper chromatography and UV spectroscopy to examine the abundance of the nucleobases, and he started to notice something VERY odd... -
Chargaff's Rules
Came to be known as "Chargoff's Rules"
Amounts of Adenine = Amounts of Thymine
Amounts of Cytosine = Amounts of Guanine
ALWAYS in EVERY SPECIES!!!
Unfortunately, Chargaff did not realize the importance of these findings; he did however share his discovery with Watson and Crick at Cambridge in 1952. -
Hershey-Chase Experiments
Used phages and radio labeled phosphorus and sulfur
Hershey and Chase concluded that DNA, not protein, was the genetic material.
A protective protein coat was formed around the bacteriophage, but the internal DNA is what conferred its ability to produce progeny inside bacteria. -
Hershey-Chase conclusions
Hershey and Chase concluded that DNA, not protein, was genetic material.
A protective protein coat was formed around the bacteriophage, but the internal DNA is what conferred its ability to produce progeny inside bacteria. -
So, it's the DNA
The race was on to determine the structure of DNA in cells and to determine how it codes for proteins and how it replicates
The problem: DNA exists in two forms
- A form (dry form)
- B form (wet form, as DNA exists in cells) -
Triple Helix?
Linus Pauling and Robert Corey proposed a triple helix structure for DNA.
The triple helix model could not be proven and was therefore discarded and did not become a "real" model. -
Eureka
James Watson and Francis Crick, 1953
Basically, when Rosalind Franklin takes photo 51, he sends it to his king's college London. The same, makes it to reach James Watson and Francis Crick who, thanks to the photo, just discover the entire structure of DNA and end up being credited with the discovery. -
The nobel prize in Physiology or medicine 1962
The Nobel Prize in Physiology or Medicine in 1962 was awarded to James Watson, Francis Crick and Maurice Wilkins for their discovery of the molecular structure of DNA, which helped solve one of the most important of all biological riddles. For the discoveries concerning the molecular structure of nucleic acids and its significance for information transfer in living material. -
DNA is a double-standed helix
The backbone is made of sugar (deoxyribose) and phosphate groups
Hydrogen bonds between the nucleobases: A-T and G-C
The sequence of nucleobases codifies the amino acid sequence of a protein.
Strings of base pairs that code for a product are called genes.