A person’s genome contains all of their genetic material and hereditary information (genes) which is passed from one generation to the next. The majority of this genetic material is located within the nucleus of a cell in structures called chromosomes which are a mixture of proteins and nucleic acids. Previously, the proteins were believed to be the genetic material and the function of the DNA (deoxyribonucleic acid) was to provide structural support.
However, this theory was challenged numerous times throughout the twentieth century leading to the realisation that the DNA is in fact the genetic material and not the proteins; but how do we know this?
Genes must be tangible; they have to be physical matter. This was demonstrated by a bacteriologist named Griffith in 1928 through the discovery of the “transforming principle”. The “transforming principle” is the horizontal exchange of genes from one organism to another completely unrelated organism (for example, if you gave your genes to your pet).
Griffith noticed that a strain of bacteria which had a smooth coat quickly killed any infected mice. Whereas a different strain of the same bacteria which had a rough coat was soon fought off by the mice. This is because the rough coat was easily recognised by the immune system of the mice so their bodies would react quickly to fight it off.
However, when dead smooth bacteria were mixed with live rough bacteria Griffith noticed the mice would die very quickly. The reason for this is that the rough bacteria had somehow gained the smooth coat meaning they could attack the mice without triggering an immune response.
This suggests that the genetic information coding for the advantageous smooth coat was passed from the smooth strain to the rough, and the only way this can happen is if genes are free physical units that can exist outside of cells and can be passed between organisms.
This theory was supported by the work of Muller. Muller devised a way to produce mutant male flies which he mated with healthy females to give offspring that possessed many genetic mutations. Through this trial and error process Muller identified that genes must be composed of physical matter and must also meet some very important criteria, all of which were properties associated with chemical matter.
In the light of Griffith and Muller’s evidence that genes are physical chemical units, further investigations took place to identify the exact carrier of genetic material that exists within cells.
Curiosity led a microbiologist named Avery to separate each chemical component of a cell. He removed the bacterial coat, dissolved the membranes and broke down all proteins until all that remained was a mysterious white substance. After conducting a range of experiments, Avery had enough evidence to claim that this unknown white precipitate, which turned out to be DNA, was in fact capable of demonstrating the “transforming principle”.
However, despite the vast amounts of evidence which indicated DNA is solely responsible for this, this discovery was greatly disputed because proteins were also present in the white precipitate. It’s like trying to identify the killer in a murder case; all evidence points towards the male being responsible however, his wife was also present at the scene - we can’t rule out the wife completely.
It was unclear as to whether the protein was necessary for and had a role in the “transforming principle” or if protein contained any genetic information. Furthermore, because the samples used (the white precipitates) were not “pure” and protein can interfere with the results, Avery’s experiments and conclusions were heavily scrutinised.
Protein interference was a huge problem. In 1950, Mazia identified that there had to be the same amount of the mysterious substance in every cell of a given species. This amount then had to change as the cell progressed through the cell cycle for example, doubling just before the cell divides and halving as the cell splits into two.
Although these experiments were successful and the amount of DNA in cells was able to be quantified, once again the presence of protein interfered with the results. However, it was established that even if the data was slightly affected by protein impurities it was clear that no protein(s) met the criteria Mazia had identified. This further supports the theory that DNA is the genetic material.
A major contribution to the acceptance that DNA contained hereditary information was an investigation carried out by Hershey and Chase in 1952. They allowed viral cells to replicate in either radiolabelled phosphorus or sulfur then infected bacterial cells. Their results showed that little sulfur and most of the phosphorus was found in the infected cells.
Only DNA contains phosphorus and only proteins contain sulfur; this means virus cells transferred most of their DNA (containing phosphorus) into the host bacterial cells but little of their protein. The scientists concluded that viruses transfer up to 85 % of their DNA into host cells from which they are able to replicate from.
So, this provided sufficient evidence that genetic material was stored in DNA, but (you know what’s coming…) unfortunately they could not be certain that no protein also entered the bacterial cell and nor could they show what exactly the DNA did.
There was still some disbelief that chemical matter was capable of transmitting hereditary information and even more speculation as to whether DNA was its carrier, and not proteins as previously believed. It was difficult to understand that a presumably simple molecule like DNA which was made up of just four different units was capable of creating the vast variety of effects generated by genes.
It made sense that proteins which can have such a complex structure and various forms were the most plausible molecules, not DNA. However, in 1953 when the discovery of the antiparallel double helical structure of DNA was made by the infamous Watson and Crick, the realisation hit. DNA was definitely capable of containing the genetic code, proteins on the other hand had other roles like in DNA packaging.
The discovery of the structure of DNA revealed exactly how this molecule can self-replicate and can contain such important information. This was the breakthrough that convinced the scientific community to finally accept that DNA is the genetic material within a cell.
This post was based on a tutorial essay I wrote in Autumn term of my first year at university. I was given the title “What is the evidence that DNA is the genetic material?”, a word limit of 1,500 and two weeks to write my first extended piece of writing since I finished GCSE English almost three years earlier. Fortunately, (by chance) I read a book by Siddhartha Mukherjee in the months leading up to starting university titled “The Gene: An Intimate History”- what a lifesaver that turned out to be!
Cobb, M. (2015). Oswald Avery, DNA, and The Transformation of Biology. Current Biology. 24 (2), 55-60.
Hershey, A. & Chase, M. (1952). Independent Functions of Viral Protein and Nucleic Acid In Growth of Bacteriophage. Journal of General Physiology. 36 (1), 39.
MUKHERJEE, S. (2016). The Gene: An Intimate History. St Ives: Clays Ltd.
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