Wednesday, 1 April 2015

DNA structure... a primer

A DNA Down Under post
For an organism, or a virus, to grow or replicate, it must make new pieces of itself and assemble those pieces into something functional.

Simple pieces or units can form larger and larger structures. In humans this process starts with proteins then moves on to form cells, then tissues, then organs and eventually whole bodies. 

In viruses the process of assembly is much shorter and less complex than in humans, with proteins assembled into a relatively simple final product, a virion or single virus particle.

So what tells the machinery of an organism to make proteins? Basically, the information is stored by a blueprint or template which is made of deoxyribonucleic acid, or DNA. DNA forms the basis of the genes of an organism or virus. But, even though DNA code has all the information needed to make proteins, it needs to be "decoded" into something that enzymes can recognise. In humans, this process is carried out by the ribonucleic acid, or RNA. RNA is a middle-man or mediator for the early steps required to produce an organism - be it a human, or quite often, a virus. RNA is also needed as a template to make more copies of the DNA. So you can see that there are two processes going on - making proteins from the DNA, and making new DNA copies from the original DNA.

What I've just described is a general, pretty simplistic plan. There are exceptions to these rules and a big one is found among viruses. Some viruses don't have genes made of DNA, they are made of RNA instead. Some viruses have thus developed special ways and workarounds to make proteins and copies of their genes. More on that later.

DNA was discovered in 1869 by Friedrich Miescher, a Swiss physician. He found an acidic substance in the nuclei of cells in pus that he named nuclein. 

It was not until 1878 that the German chemist Albrecht Kossel purified the protein away from these nucleic acids, and also later identified its nucleobases (see above) - or component parts.

A pentose sugar (middle) attached
to a monophosphate group (left) 

and the site where a purine or 
pyrimidine nucleobase attaches (right). 
Nucleoside=sugar + base;
Nucleotide=sugar + base 

phosphate group
In 1919 the Lithuanian-American chemist Phoebus Levene identified that units of DNA (a nitrogenous base, a sugar and a phosphate; right) associated into chains. In 1937 these structures were first revealed through X-Ray diffraction thanks to English physicist and molecular biologist, William Astbury. In 1952 Dr Rosalind Franklin captured images of the patterns DNA crystals made when scattering X-Rays. In 1953 American molecular biologist James Watson and English molecular biologist Francis Crick proposed the double-helix model of DNA structure, based on an X-ray diffraction image.

Nucleic acid is one of several macromolecules (big molecules) found in the body (others include proteins and carbohydrates) which are formed by lots of individual molecules (nucleotides) strung together to form a polynucleotide. Each nucleotide consists of a sugar, a nitrogen base and a phosphate group. In RNA the sugar is called ribose (how the name ribonucleic acid comes about), and in DNA it is called deoxyribose which means that it is missing ("deoxy") a carbon atom compared to a ribose sugar.

The combination of a sugar with a any one of five different nitrogen bases creates a nucleoside. The five bases are divided into two categories based on the structure of their molecules; purines have two ring structures (adenine and guanine) while pyrimidines have one (thymine, cytosine and uracil). Adenine, guanine, thymine and cytosine are found in DNA whereas RNA replaces thymine with uracil.

If a phosphate molecule is added to a nucleoside it becomes known as a nucleotide. Nucleotides with a ribose sugar are therefore ribonucleotides, and nucleotides with a deoxyribose sugar are deoxyrobonucleotides. Each nucleotide's name can be shortened to a single letter, A for adenine, C for cytosine, G for guanine, T for thymine and U for uracil.

The chemical bond that links one nucleotide to another is formed between the phosphate group of one nucleotide and the sugar group of the next nucleotide via an ester bond between a carbon atom and an oxygen atom. Two things remain the same no matter how many nucleotides are added to the growing polynucleotide chain; one end of the chain has a free phosphate group and the other end has a free hydroxyl (-OH) group. These ends are called 5' ("five prime") and 3' ("three prime") respectively (there's no Optimus prime).

This naming system comes from the way we present a sugar structure when we draw it on paper. We start at the "top, right-hand" carbon and count in a clock-wise manner. The phosphate group of the previous nucleotide is linked to carbon number 5, and the phosphate group of the next nucleotide is linked to carbon number 3. The naming system, 5' to 3' is used to describe the order of the nucleotides in the DNA strand. Think of the system as being similar to the way European people are taught to read and write - from the left side of a page to right side.