MOLECULAR BIOLOGY

Intro: One thing common to all life on Earth, from bacteria to blue whales to bonobos, is a genetic code contained within strands of DNA. This leads to the perplexing question of how our DNA creates human beings.

LONG sections of genetic code are identical across the entire span of life. About 50 per cent of our own DNA sequence is the same as bananas’, while we share 98 per cent of our DNA with chimpanzees. So, what makes us different?

In April 2003, a major milestone in the study of human genetics was reached with the publication of the complete human genome. An enormous collaborative project worked on by scientists in 20 different countries, it may well come to be regarded in the same light as the great scientific landmarks. Principal among these was the work of the Augustinian monk Gregor Mendel – often referred to as the “father of genetics” – which he carried out in the 1850s and ‘60s and which first established the rules of heredity, as well as James Watson and Francis Crick’s 1953 description of the molecular structure of DNA as the now-famous double helix.

Gene Expression

The published genome contains the sequence of some three billion so-called base pairs, which constitute the genetic code in our DNA. The translation of the code made up by these base pairs is used to build up 20 different essential amino acids which, together with other amino acids we get from our food, combine in numerous different ways to form all the different proteins we require in our bodies. Geneticists used to think that the role of DNA was almost entirely concerned with providing a template for the manufacture of these proteins, but the complete genome showed that the sections of DNA which perform this function, our genes, only account for about two per cent of the total.

The function of the remaining 98 per cent, sometimes known as “junk DNA”, is not entirely known, but it has become increasingly apparent that much of it is not junk at all. It plays a role in, among other things, gene expression. This is the actual process by which the information contained in our genes is used to make up all the different tissues and organs in our body, through the process known as cell differentiation. Here, stem cells divide to produce different types of cells, such as liver cells or nerve cells. Unravelling the way in which one type of cell divides to produce a wide variety of different cells has proved to be extremely difficult and is currently one of the principal areas of genetic research.

The basic functioning of DNA in producing amino acids from the genetic code is relatively straightforward: the double-stranded DNA molecule effectively unzips, splitting apart the base pairs and revealing the code that is then copied by single-stranded RNA and used to assemble amino acids. But the control of this process, in which the required genes are activated and those not needed switched off, appears to be extremely complicated. Each advance in our knowledge of gene expression uncovers a whole new level of complexity that has to be unravelled. Beyond that, there is also the equally tricky problem of determining how, during the process of protein folding, the proteins made from genes assume the three-dimensional shape that determines their functions. The potential applications of our advancing knowledge of gene expression and protein folding are wide, not least in increasing our understanding and ability to treat diseases which have a genetic basis, prominent among which are many forms of cancer.

The Difficulties of Cloning

Another landmark in genetic research was achieved in 1996, when the first mammal (known as Dolly the Sheep) was cloned by geneticists at the University of Edinburgh in Scotland, using a technique called somatic cell nuclear transfer. This involves the removal of a nucleus containing genetic material from a cell of the animal to be cloned, and its introduction into an egg from which the original nucleus has been removed. The egg is then implanted into a surrogate mother and, in theory at least, will develop into an embryo with DNA identical to the animal from which the nucleus was taken.

Needless to say, if it were as easy as that, cloning would be a common occurrence today. In reality, it has proved much more difficult, in part because of the complications which arise as a consequence of gene expression. In some successful cloning experiments, for instance, the observable traits, or phenotype as it is known, of the cloned offspring are not always the same as those of the original animal. So, despite being genetically identical, the offspring looks different from the parent. In order to produce exact copies of the original, the process of cloning has to solve the complicated issues involved with gene expression, including the role of junk DNA in regulating genes. We are, it appears, a long way from seeking flocks of cloned sheep.

Alternative Theories

In recent years, it has become increasingly apparent that gene expression is not controlled solely by DNA but is also influenced by a number of external factors collectively known as epigenetics. This is a new field of scientific research and the details of how it works are disputed, but, in essence, it implies that the environment in which DNA replication occurs during cell division can influence the activity of genes and, in doing so, can have an effect on the resulting phenotype. This is thought to occur at a molecular level, through environmental factors modifying the actions of those proteins that surround strands of DNA and influencing the switching off or activation of genes. These epigenetic modifications do not change the DNA sequence of base pairs, so are not inherited by future generations, even if those generations may then be subjected to the same environmental conditions as the parent, resulting in similar epigenetic modifications.