Ask any biochemist, and they’ll have definitely heard of the term “DNA”. And as much as how it is such a common term thrown around in the world of life sciences, it would be a great idea to get some basic understanding of how the DNA was discovered. Or if you’re new to this term, let’s have a quick run-through on what it is.
What is DNA?
You probably would have come across the term “genome” when you learnt about the existence of DNA. Essentially, your genome is the complete recipe book of genetic instructions, which are used to construct your body and provide directions on how your body will grow and mature. This magnificent genome is made of the deoxyribonucleic acid (DNA) and its length is approximately 3,000,000,000 base pairs long! Meanwhile, your DNA is the hereditary material in most organisms. They basically encode the instructions to synthesize all the proteins that are essential for life.
All DNA instructions are made of four bases, or chemical building blocks to put things simply, which are adenine (A), cytosine (C), guanine (G) and thymine (T). These bases serve as the simplest unit of the genetic cues encoded by our DNA to direct the construction of an organism.
To focus on the general overall structure of a DNA, it is basically a double-stranded molecule with a twisted ladder shape, more popularly known as the “double helix”. Each strand would have a beginning called the 5’ (pronounced as “five prime”) end, and an end known as the 3’ (three prime) end. In essence, these two strands run in opposite directions whereby one strand runs from the 5’ to 3’ end (and thus called the sense strand), whereas the other is called the antisense strand as it runs from the 3’ to 5’ end. As a result, the DNA strand pairing is known to be of an “antiparallel” nature.
Not to mention, the bases present on each DNA strand will pair together with one of the bases located on the other DNA strand. Though it is important to note that the pairing is specific, as adenine will only pair with thymine, whilst cytosine can only pair with guanine.
Hence, the final structure of the DNA appears to be a ladder, with both strands joined together via hydrogen bonds, which is a strong intermolecular interaction that holds the two DNA strands together to maintain the DNA’s double helix structure.
The origins of DNA
Come to think about it, writing the previous paragraph would not have been possible - if it weren’t for the magnificent discoveries made by some of the most brilliant scientists in the past. So, it would be extremely important for us to not take our knowledge of DNA for granted and to delve a little deeper into the journey of discovering DNA and its structure.
Friedrich Miescher
Much of the research into nucleic acids started out thanks to a Swiss physician and biologist called Friedrich Miescher. He was the guy who first discovered “nuclein” within the pus that was collected in the bandages of wounded patients back in 1869, whereby he managed to extract this chemical substance using mild alkali. Mr Miescher eventually showcased that this “nuclein” was rich in phosphorus and was located within a cell’s nucleus.
Phoebus Levene
Mr Levene was essentially the guy who, in 1929, discovered the four nucleotides (A, C, G, and T) of DNA. He also demonstrated that the DNA is made up of three key chemical constituents, namely a deoxyribose sugar, a phosphate group, and a nitrogenous base. Upon his discovery, he simply postulated that this structure is way too simple to be a hereditary material that directs key biochemical processes that maintain life on Earth.
Frederick Griffith
Back in 1928, Mr Griffith demonstrated that a Gram-positive bacteria called Streptococcus pneumoniae could be converted from a “rough” phenotype to a “smooth” phenotype, by applying a genetic technique known as transformation. This was popularly recognised as Griffith's experiment.
Oswald Avery, Colin MacLeod and Maclyn McCarty
Meanwhile, it was the Avery–MacLeod–McCarty experiment, conducted by Oswald Avery, Colin MacLeod, and Maclyn McCarty 16 years later, that built upon the results from Griffith's experiment to showcase that DNA is the key component that made bacterial transformation a possibility.
Hershey and Chase
Strangely, many people still didn’t buy into the notion that DNA was responsible for transformation, despite the rather convincing data presented by the Avery–MacLeod–McCarty experiment.
To effectively convince the sceptics, Alfred Hershey and Martha Chase famously used a kitchen blender that they borrowed to prove that DNA plays a genetic role within bacteriophages.
Erwin Chargaff
A paper published in 1950 and penned by Mr Chargaff provided an important clue to its structure. In particular, he identified a pattern in the composition of nucleotides, in which the content of adenine is usually the same as thymine, whereas the amount of guanine would be identical to cytosine.
This ultimately led to the proposition of Chargaff’s rules for specific base-pairing, which explains that adenine always pairs with thymine, and cytosine will always bind to thymine. This could be accomplished due to these two base pairs having specific hydrogen bonds between them, with the A=T pair having two hydrogen bonds, whilst the G≡C pair having three hydrogen bonds instead.
Other than that, Mr Chargaff also purified DNA from various human tissues, bacteria, yeast, and several cows. After performing in-depth chemical analysis, he eventually realised that the guanine-cytosine (G≡C) content of DNA varies between different species. This provided evidence to further strengthen the case that DNA was indeed the hereditary material for organisms, as each species he investigated had a unique DNA composition.
Franklin, Watson and Crick
Under pressure of a race against their rival, Linus Pauling, Watson and Crick brought forward the idea that the DNA had an antiparallel double helix structure in 1953. This notion was made based on the X-ray diffraction data (famously known as Photo 51) produced by Rosalind Franklin in combination with the works of Mr Chargaff. Soon enough, this proposition eventually landed them the Nobel Prize in Physiology/Medicine later in 1962.
Nevertheless, it is important to realise that Watson and Crick did not actually perform any of those experiments as they only made models based on Franklin’s data and results from previous investigations on the DNA.
Interestingly, Mr Pauling did actually publish a paper only a few months before Watson and Crick did. He proposed that DNA may have a triple helix structure consisting of three parallel strands with its bases located on the outside. However, Crick quickly realised that this was incorrect as this would mean that the phosphate groups will be found in the centre of the helix, and this structure would therefore not be viable because their intrinsic negative charges would repel each other and tear down the overall structure.
Why should you care?
It has been largely debated that the discovery of DNA and its function as well as structure could be the most critical discovery in the previous century!
Though, why would someone say that?
To put things into perspective, DNA holds the manual to generate proteins that direct genetic processes governing life. It is essential for the development of cells as well as reproduction amongst organisms.
DNA is also the key factor responsible for death, if nature messes up its production. A great example would be single nucleotide polymorphisms (or SNPs in short; pronounced as ‘snips’), which are a type of error that may occur during DNA replication. This may ultimately result in a different protein being produced. For instance, certain SNPs can alter the way you look or even cause diseases such as sickle cell anaemia and cystic fibrosis.
To further emphasize our point, having different genetic makeup would determine certain things like whether you can tolerate lactose or not, your metabolism rate, or even which skincare routine or workout regime would suit you best!
Therefore, it is pretty clear that understanding the DNA structure plays an enormous role in boosting the progress we’ve made in healthcare, whereby we may soon be able to design drugs intended for personalised genomic medicine.
Author
Bianca Khor
BSc Biochemistry
Imperial College London