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Chemistry in Genetics

In this age of rapidly evolving technology, DNA sequences can be analysed by computers, and machines can separate hundreds of proteins at once. This makes it is easy to forget that the genetic code isn’t simply a series of letters, and that proteins aren’t just what we get out of eating poultry. They are physical and chemical structures that build and care for our bodies.

The building blocks of DNA are known as nucleotides, and are comprised of three main parts: a phosphate group, a sugar, and a highly-charged unique nitrogenous base. Of the four bases, adenine (A) and guanine (G) are both purines, which consist of an aromatic ring attached to an imidazole group. The other two bases, cytosine (C) and thymine (T) are pyrimidines, made up of a single aromatic ring. It is widely known that in DNA, A pairs with T and G pairs with C, but why is this?

The first thing to address is what ‘pairing’ actually means. Imagine the entire nucleotide with its sugar, phosphate, and highly-charged hydrophobic base. The molecule will want to bury its hydrophobic base, to shield it from water. The best way to do this is to bind another nucleotide’s base to its own, with protective sugar phosphate groups flanking either side. But why are the bases always paired the same way? The answer is in the chemistry of their compositions.

Adenine and thymine both have two charges, one positive and one negative, arranged opposite each other. This allows the two bases to form two strong and stable hydrogen bonds. On the other hand, cytosine and thymine each have three charges: guanine has two positive and one negative, and cytosine has two negative and one positive. Similar to the previous case, this allows the two bases to form three strong and solid hydrogen bonds. The complementary nature of the two sets of bases is as if they were paired together like sets of socks. An entire genome is made up of millions of these ‘base pairs’.

Starting with the structure we’ve just described: a phosphate-sugar-base-base-sugar-phosphate. How do we move from this ‘slab’ to the entire DNA double-helix? Firstly, these slabs are stacked on top of one another, which further buries the inner hydrophobic bases. This stacking occurs when the phosphate of one nucleotide binds to the sugar of another, a process that can be repeated ad infinitum, creating what is commonly known as the ‘sugar-phosphate backbone’. As luck chemistry would have it, these sugar-phosphate, or phosphodiester, bonds are extremely hydrophilic, loving to be immersed in water, which further protects their hydrophobic bases.

These phosphodiester bonds begin to give us a ladder type structure that resembles the recognisable double helix, but not quite. The DNA double helix structure is the result of further acts of geometry and chemical interactions. There are a large number of tweaks, turns, and bends that can be performed on the internal base pairs, with the sole purpose being the ultimate protection for these hydrophobic bases from water. Once the base pairs are fully protected, these adjustments give DNA its characteristic helical shape, ready to be translated into proteins.

Like DNA, proteins are made up of small building blocks: the 20 amino acids. Each amino acid is comprised of an amine group, a carboxylic acid, and a unique side chain arranged tetrahedrally around an α-carbon. Special properties of the unique side chain-like chemical hydrophobicity, charge, and size will eventually determine the overall shape and therefore the function of a protein.

For example, hydrophobic amino acids will want to be buried in the core of the protein and small amino acids will be able to fit in small pockets to interact with other proteins. Forms of the amino acids cysteine, serine, and threonine allow them to act as nucleophiles. On the other hand, the amino acid tryptophan allows a protein to absorb ultraviolet light. Some amino acids have higher melting points because they can form exceptionally strong bonds thanks to their ‘zwitterionic’ nature — two different electrical charges within the same molecule. With an α-carbon and four distinct substituents (except for glycine, which has a hydrogen as its side chain), 19 of the amino acids are ‘chiral’, which means they have four unique side-chains surrounding a central carbon, and every single one of them is left-handed, meaning that the side-chains stick out in the same way way. Scientists today are still debating why and how this ‘homochirality’ arose in life on Earth.

Chemical actions form the structure of DNA. This structure is just the foundation for thousands of processes such as DNA transcription, translation, inheritance, cell division, and the expression of proteins, which are all governed by chemistry. These processes are critically important, but none of them would be possible without the complex structure of DNA, because as any geneticist will tell you: structure determines function.

Kaitlyn Martin is an undergraduate student in genetics

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