DNA Mutations Can Help Personalize Medicine, New Study Shows

As humans, we like to think our genes are of a superior calibre and rarely mutate – especially if we are fit and healthy. Despite this, new research reveals that natural genetic mutations are more frequent than originally thought, which (although in extreme incidents lead to diseases or other problems), can provide further insight into the mechanisms that are necessary for adaptation to the environment.

Many of the characteristics that make you an individual, ranging from the colour of your hair and eyes to how susceptible you are to developing certain diseases, are determined by the genetic material (long strands of DNA) inherited from your parents. Certain sections of DNA – known as genes – contain molecular sequences that enable proteins, the basic building blocks of life, to be assembled. However, the DNA sequences that comprise genes are not always perfect and can be prone to change. These changes, known as mutations, often lead to negligible or unnoticed traits in an organism, although some do result in significant alterations, which can be beneficial or harmful. Those altered genes that are damaging often result in death and are subsequently removed from the gene pool; while those that are deemed favourable can increase the likelihood of an organism’s survival, providing a greater chance for such genes to be passed onto the next generation and help continue the success of a species.

Normal Imperfections

No one is perfect. We are either too fat, too short, have skin problems, lose our tempers too easily or are prone to disease. These imperfections, however, are vital for our species. Variation is necessary for allowing a species to continue, with the better suited individuals within a population having a greater chance of survival in a given environment at a particular time. This process leads to adaptation, and when – over geological time – environments change, those individuals that are better adapted to the environmental shift are more likely to survive. This can ultimately lead to the development of new species. It is easier to accept these changes in micro-organisms and plants; yet when we start to consider such occurrences in animals, and particularly birds and mammals, we often find these ideas more challenging for a variety of different reasons. Nevertheless, new studies indicate that we all carry imperfections in our genetic make-up and that this is a normal phenomenon.

Genes are sections of DNA that are transcribed by an associate molecule called RNA. Following this process, another type of RNA translates the DNA-copy into a sequence of amino acids, and this string of amino acids forms a protein, the fundamental molecular structures that comprise all plant and animal bodies. Therefore, changes in a DNA sequence can lead to alterations in the make-up of a protein. When an organism develops at the embryonic phase, certain genes activate, which allows for the manufacture of proteins that construct basic body architectures. These proteins that are produced can also further activate dormant genes, while other proteins deactivate genes that are in operation. The time during which a gene is activated can have a significant effect on the characteristics of an organism. For instance, the genes that are responsible for the length of the hind-limbs in a vertebrate embryo will be activated for a longer period in a horse, cow or giraffe than in a frog, tortoise or mouse – and not at all in a snake or dolphin – before they are deactivated by proteins (produced by other genes) that stop the hind-limb building genes from assembling proteins. These proteins that communicate with genes depend on the DNA sequences that assembled them, so a change in this sequence – a mutation – will affect the functioning of the proteins and this can ultimately alter the anatomy and physiology of an organism.

It is also known that genes do not always operate by themselves. In the Soviet Union during the 1950s, an experiment was designed to understand how humans domesticated the wolf-like ancestors of the modern dog. This breeding experiment used Siberian silver foxes, which had never been domesticated previously. Foxes were collected from local fur farms and from this population the friendlier and more docile individuals were selected and bred together – a process that continued with the subsequent offspring, and so on. The outcome of this research revealed that not only did a population of artificially selected foxes become tamer around humans and choose to seek human company; the results also revealed that after only nine generations, the physical characteristics of the animals also dramatically altered. These included drooping ears, curly and wagging tails, vocal cries for attention and white blotch- and spot-markings in the fur pattern – traits not found in wild animals. This indicates that genes for one trait can influence other genes that are responsible for different characteristics. Therefore, a genetic mutation at the embryonic phase could produce proteins that influence the genes they activate, which could then affect yet other genes and their functioning, and thus further variation. Research is now trying to locate the genes for tameness in foxes, dogs and other animals – it will be interesting to see whether similar genetic processes exist in humans and, if so, whether they influenced our characteristics when we became domesticated during our own biological history. 

Advancing Medicine

Located in Cambridge, England, the Wellcome Trust Sanger Institute is a major participant of an international consortium that forms the 1000 Genomes Project. This project has recently decoded and mapped the genetic sequences of over 1,000 apparently healthy human individuals from the Americas, Europe, Africa and Asia to understand what genetic processes can lead to variation within a population, and gain further insight into the development of genetic diseases, such as cancer and diabetes. From this research, the genetic sequences of 179 individuals were compared with a database of diseases caused by genetic mutations (which can occur naturally when errors are made during the transcription and translation of DNA) from Cardiff University in Wales. The results revealed that on average there were 400 possibly harmful DNA mutations among the participants who were sampled, including two changes in the genetic material that are known to be associated with disease. However, these mutations often cause no harm to the individual and may only pose a risk later-on in life, or if they are inherited by offspring, who also inherit the corresponding detrimental genes from the other parent.

These findings could be used in personalised medicine techniques, which are predicted to become more available in the future. Indeed, it is the concept of biological variation that supports the idea of personalised medicine – if there are no mutations in our genes then there would be no need for personalised treatments. To enable this form of medicine, the genetic make-up of an individual would be examined to see what diseases they are likely to encounter during a typical lifetime. It is predicted that specialist companies will be able to offer screening techniques that will pinpoint specific harmful gene mutations. Although there are many benefits to these anticipated gene sequencing methods, the questions of ethics also need to be considered, especially as this is still a new field of genetic science and biotechnology. Accordingly, it is important to regulate this approach to reduce harm to biological systems, and potential patients should be aware that this warning system is not a guarantee and that the results – although useful for doctors – could come as an undesirable surprise. 

Faulty Genes and Biological Adaptation

The outcomes from the 1000 Genomes Project not only allow for advancements in medical research and future personalised medicine possibilities. It also demonstrates the scope of genetic variability that is found within all organisms, including ourselves, which can be visible to the observer or concealed at the genetic level, and that such variation is a normal occurrence. If a population is given time to progress – and has a restriction on the migrations of individuals or external genetic inputs – some of the more advantageous gene mutations, which can enable a greater chance of survival within the surrounding environment, could accumulate, leading to not only variation within the given population but also adaptation to suit their surroundings. And the complex and interlinked genetic processes, which allow variation and adaptive progression to occur, take place in all micro-organisms, plants, fungi and animals, including human beings. Indeed, these new findings can also provide insight into the development of our own species, helping us to understand the biological mechanisms that enabled the individuals that formed the population of our ancestors to survive and progress – events that set the genetic foundations for our history.