The fact that DNA is the key hereditary material is well established now. But it’s worth wondering how this crucial bio-molecule positioned itself at the center of biology.
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The discovery of the nucleus within a cell itself is a milestone. Later it was observed that the nucleus of the cell and chromosomes have something to do with transferring heredity. But the early scientific evidence was highly unconvincing. Scientists only made the first conclusive evidence that chromosomes were responsible for gene transfer when they observed that the variation in the number of chromosomes among organisms. The fact that the number of chromosomes constant in all the cells within an organism, and varied among cells of different organisms came out a big surprise.
But more surprising is the fact that DNA was considered highly unconvincing to be the genetic material because of its low chemical diversity. DNA contained only phosphates and nucleoside. Instead, Proteins were considered an ideal candidate as they were chemically diverse and had a huge variety of compounds. But the following experiments brought researchers into finally accepting DNA as the key genetic element.
Friedrich Griffith Experiment (1928)
Frederick Griffith (1879–1941) was a British bacteriologist whose focus was on the epidemiology and pathology of bacterial pneumonia. Griffith played with two strains of Streptococcus pneumoniae, of which one strain(S or Smooth) produced Pneumonia while the other strain(R or Rough) didn’t. The ability of the S-strain to induce disease was due to its ability to produce a capsular polysaccharide coating. This outer polysaccharide coat enabled the bacteria to conceal itself from being detected by the host immune system, which otherwise would get targeted and killed.
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Griffith injected mice with living R strains and heat-killed S strains and expected the mice to remain healthy. But the mouse developed pneumonia instead. He then isolated the bacteria from the blood of infected mice from which S-strains of the bacteria were isolated. This implied that there must be a genetic material in the heat-killed S-strains of bacteria and a mechanism to transfer this material from dead S-strain of bacteria to the living R-strains which as a result, changed the non-virulent R-cells to virulent S-cells.
Oswald Avery, Colin MacLeod and Maclyn McCarty (1944)
Griffith’s experiment in 1944 was further illuminated by the discovery of DNA’s role in the transformation process. Only then it was concluded that DNA was the material that transferred from one cell to other eventually changing R-strains into S-strains.
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In their experiment, for the first time, researchers isolated almost pure DNA from S-cells and mixed this extracted DNA with the culture of R-cells. They observed the transformation of R-cells into S, and thus confirmed the role of DNA in genetic transformation. Furthermore, they discovered that the transformative ability was not altered by the destroying proteins (by using Proteinase) and RNA (by using RNAse) in the DNA isolate, but this ability was completely lost by when DNA was destroyed. This experiment by the trio researchers proved DNA to be the genetic material.
3. Hershey and Chase (1952)
Alfred Hershey and Martha Chase studied the role of DNA in genetic information transfer by experimenting with T2 Bacteriophage. A bacteriophage is a virus that infects the bacteria. It was known to the researchers that the phage attaches itself to the surface of the bacterial cell with the help of its tail and injects itself inside the bacteria.
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It was also known that DNA contains Phosphorus and Protein contains Sulphur, which formed the basis for differentiating DNA from Proteins. Hershey and Chase used radioactive isotopes of Phosphorus and Sulphur for proving that DNA indeed is the genetic material, even in viruses. In their experiment, several generations of E. coli were grown in media containing 32P and 35S to produce viral progeny containing these isotopes in their DNA and Proteins.
After this, the non-radioactive E. coli cells were mixed with phage particles labeled with 32P and 35S separately. The phage particles rapidly attached to the surface of E.coli after mixing. The unattached phage particles were removed by centrifugation. Furthermore, the phage particles from the surface of the cells were also sheared off by a violent stirring with a kitchen blender.
Despite the rapid decapitation of the virus from the cell surface by vigorous blending, a subsequent amount of virus infection was observed in the bacteria. This implied that the genetic material of the phage enters the bacteria soon after attachment.
As a result, a high amount of 32P isotopes (~50%) were inherited by the progeny phage particles, which was observed in the cells. However, a low amount of 35S isotopes(~1%) was detected. This proved that DNA is the genetic material in T2 Bacteriophage and was readily transferred in the viral progeny. The experiment also cleared protein from the generalization of being presumed as genetic material.
Reference:
Hartl, D., & Jones, E. (2001). Introduction to molecular genetics and genomics. Genetics: analysis of genes and genomes, 5th edn. Jones & Bartlett, Mississauga, ON, Canada, 1–35.
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