Animal Aid

Man or Mouse

Genes and Proteins: A Brief Introduction

What's in a gene?

Mouse

All living creatures are made of cells; some are made of just one, others of many billions comprising hundreds of specialised types collectively organised into tissues and organs. All cells are basically small, fluid compartments containing a concentrated solution of chemicals, along with various structures that help the cell to stay alive, replicate and perform its necessary functions.

Almost all cells have in common a nucleus, a separate compartment within the cell containing DNA (deoxyribonucleic acid). This DNA, made up of building blocks known as nucleotides (of which there are four types), takes the form of the famous twisted double helix, and coils upon itself time and time again to form discrete bodies called chromosomes. Humans have 46 chromosomes (23 pairs) in the nucleus of each cell of their bodies, which together make up what is known as the human genome. The only exceptions are egg and sperm cells, which contain 23 single chromosomes not in pairs: this allows the chromosomes to 'pair up' again when the sperm and egg unite during fertilisation to make a new embryo with the normal number of chromosomes - half coming from each parent.

If one imagines the DNA strung out in a long line, it is composed of tens of thousands of units along its length known as genes. These genes serve as a template for the cell to manufacture the proteins and enzymes that make up our bodies and keep it alive. This occurs via two processes known as 'Transcription' and 'Translation'.

In transcription, pieces of 'cellular machinery' known as enzymes engage with the DNA, and track along the double helix making a copy of the DNA, but in a chemically slightly different form known as RNA. This RNA is then used as a template for the translation process, whereby other bits of cellular machinery 'translate' the RNA code in order to assemble amino acids into chains known as polypeptides. These, in turn, make up the all-important proteins (Figure 3).

Gene Expression: An exquisitely controlled process

The process whereby genes serve as a template for the cell to make proteins is called gene expression. Genes are classified as 'Structural' or 'Regulatory,' depending on their function. Structural genes code for proteins that 'make up' our bodies; that build our cells and organs, and that form enzymes that carry outchemical reactions vital for life. Regulatory genes control the expression of structural and other regulatory genes, increasing and decreasing their levels of activity or turning them 'on' or 'off' completely.

This is a very tightly controlled process involving inputs from many angles, and a minor fault in any of the components or processes can have far reaching effects and be the cause of many diseases. For example, if the DNA template is damaged or altered in some way, such as by a harmful chemical, radiation - or if a damaged version is inherited from one's parents, then the protein will not form or function correctly. Sometimes, the enzymes that carry out gene expression, which are themselves products of other genes, will themselves malfunction. Pieces of DNA flanking the actual genes are also of crucial importance, acting as extracontrol elements - in concert with the products of the regulatory genes - to modulate gene expression. Again, a small fault or minor difference can have far-reaching consequences.

It is important to note that the protein products of genes do not go about their jobs in isolation; there is an almost infinitely complex array of interactions between them and other cellular components that can alter their functions drastically. Many of these protein complexes interact with the aforementioned DNA 'switches' to change what they do. Furthermore, one gene can actually give rise to many different proteins, which have varied functions and interaction partners. (Examples include 'RGS'[2] and 'CREM'[3] genes involved in signalling between cells, tissues and nerves, responses to hormones and sensory inputs etc). Additionally, the machinery responsible for these processes differs between species. Genetics is a very complex business!

These factors illustrate how enormously difficult it is simply to alter a gene in an animal, and then expect to see precisely what that alteration means in that particular species, and then to be able to deduce what that means in a human context. We can also see that similar genes in different animal species can do different jobs in different ways, and that the generation of genetically modified animals, by their very nature, is a highly complicated, difficult, imprecise, inefficient and crude method (in terms of results) of determining or altering the function of a gene.

Increasingly we are discovering that the, genetic similarity between humans and chimpanzees (around 95%-98%, depending on whose estimates you believe) means little: after all, we are quite clearly not chimpanzees, and vice-versa. Mice are thought to share 95% of our DNA, and tiny nematode worms about 70%. Superficially then, it seems that the small difference between our genes has anything but minor consequences. As scientific knowledge increases, we are learning that such minimal changes in DNA sequence lead to profound differences in biochemistry and physiology and this, occurs predominantly due to variation in the regulatory genes and DNA regions described above.

So no matter how similar our structural genes may be, if they are regulated differently, we're looking at a whole new scenario. One simple analogy of this isto imagine two huge, complex and almost identical church organs side-by-side. The hundreds of stops either side of the keyboards are the regulatory genes and regions of our DNA, able to exert subtle changes in the sound of the instruments individually but also able to act in, countless combinations together to alter the sounds drastically. Even if the same music is played on both organs, the sound will be entirely different unless the stops (i.e. the regulatory genes and regions) are in identical positions. Change the order and timing with which the keys are operated, and the end products are completely unrecognisable from one another.

Click here for part 3 of Man or Mouse.

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