The Search Narrows
Now it had to be determined which component of the chromosome, DNA or
protein , was the genetic material. Many scientists were sure that it
was protein. After all, there were so many subunits (20 amino acids)
that it seemed obvious that there existed within protein the
possibility for much more diversity in expressing the genetic code
than in DNA, which only has 4 subunits. DNA was considered a boring
The Discovery of DNA
DNA was first identified in 1868 by Friedrich Miescher, a Swiss
biologist, in the nuclei of pus cells obtained from discarded surgical
bandages. He called the substance nuclein, noted the presence
of phosphorous, and separated the substance into a basic part (which
we now know is DNA) and an acidic part (a class of acidic proteins
that bind to basic DNA).
The Transforming Principle - DNA Might be the Genetic Material
In 1943, Oswald Avery, Colin Macleod, and Maclyn McCarty, at the
Rockefeller Institute, discovered that different strains of the
bacterium Strepotococcus pneumonae could have different effects
on a mouse. One virulent strain could kill an injected mouse,
and another avirulent strain had no effect. When the virulent
strain was heat-killed and injected into mice, there was no effect.
But when a heat-killed virulent strain was coinjected with the
avirulent strain, the mice died. What transforming principle
was the dead virulent strain giving to the avirulent strain to make it
Avery and his colleagues separated the dead virulent cells into
fractions and coinjected them with the avirulent strain, to see which
fraction contained the transforming principle. They discovered that
the fraction was DNA. Most scientists at the time, in favour of the
theory of protein as genetic material, discounted this result and said
that there must have been some protein in the fraction that conferred
The Hershey-Chase Experiment - DNA is the Genetic Material
Finally, in 1952, Alfred Hershey and Martha Chase performed the
definitive experiment that showed that DNA was, in fact, the genetic
material. Recall the mechanism of bacteriophage infection. By radiolabelling
sulphur in one culture, they could tag the path of proteins and not
DNA, because there is no sulphur in DNA and there is sulphur in the
amino acids methionine and cysteine. By radiolabelling phosphorous,
the opposite effect could be achieved. DNA could be traced and not
protein, because there is phosphorous in the phosphate backbone of DNA
and none in any of the amino acids. Cultures could be grown in each of
these two ways and the phage purified away from the host bacteria,
resulting in one culture in which only the phage protein was labelled,
and one culture in which only the phage DNA was labelled.
Side by side experiments were performed with separate phage
cultures in which either the protein capsule was labeled with
radioactive sulfur or the DNA core was labeled with radioactive
- The radioactively labeled phages were allowed to infect bacteria.
- Agitation in a blender dislodged phage particles from bacterial cells.
- Centrifugation pelleted cells, separating them from the phage
particles left in the supernatant.
Thus, it was shown that the genetic material that encoded the growth
of a new generation of phage was in the phosphorous-containing DNA.
- Radioactive sulfur was found predominantly in the supernatant.
- Radioactive phosphorus was found predominantly in the cell
fraction, from which a new generation of infective phage was generated.
Chargaff - Nucleotide Content in DNA
Now that it had been established that DNA was the genetic material,
scientists began fervently looking for its mechanism and structure. In
1950, Erwin Chargaff at Columbia University discovered that no matter
what tissue from an animal he looked at, the percentage content of
each of the four nucleotides was the
same, though the percentages could vary from species to species. This
insinuated that the structure of the DNA was specific and conserved in
each organism. He also found, more importantly, that in all animals:
%G = %C
%A = %T
The significance of these results was overlooked for three years, but
they were crucial to elucidating the structure of DNA.
Watson and Crick - The Double Helix
In late 1953, James Watson and Francis Crick presented a model of the
structure of DNA. It was already known from chemical studies that DNA
was a polymer of nucleotide (sugar, base and phosphate) units. X-ray
crytallographic data obtained by Rosalind Franklin, combined with the
previous results from Chargaff and the chemists, were fitted together
by Watson and Crick into the following model:
In the double helix the two strands of DNA run in opposite
directions and are complementary, being matched by the hydrogen bonds of
the A - T and G - C base pairs. This complementary pairing of the bases
suggests that, when DNA replicates, an exact duplicate of the parental
genetic information is made. The polymerization of a new complementary
strand takes place using each of the old strands as a template.
For their outstanding work in discovering the double helical
structure of DNA, Watson and Crick shared the 1962 Nobel Prize for
Physiology and Medicine with Maurice Wilkins. Sadly, Rosalind Franklin,
whose work greatly contributed to this key discovery, died before this
date, and the rules do not allow a Nobel Prize to be awarded
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