TRANSPOSONS - your 'Jumping Genes', good and bad

Never heard of them? Don’t worry; most medical practitioners haven’t heard of them either. Why would you want to know about transposons, anyway?

Wait for it! Because transposons are part of you. They are in your DNA. And in the DNA of every other human who has ever existed. And they are not going to go away. Nor would you want them to.

By 2001, advances in technology allowed scientists to examine our DNA in unprecedented detail by the process of ‘genome sequencing’. They were amazed to discover that only 1-2% of our DNA made up our genes. Recall that your genes largely determine who you are – your eye colour, blood type, your height and so on. Without a known function, the remaining 98% was uncharitably dubbed ‘junk DNA’. Then more amazingly, it was noted that around 10% of our DNA is identical to viral DNA.

Furthermore, much of the rest is virus-like components. Some virus-like elements can leap from place to place in our genomes, often making copies of themselves and acquiring mutations. Think of them as ‘jumping genes’. Scientists coined the term ‘transposon’ to describe them. Incredibly, transposons account for about 35% of our genomes. So all-in-all, some 45% of your DNA originated in viruses! How did this comes about?

Viruses have infected probably all living organisms since life first arose on earth. Humankind has likely weathered numerous viral epidemics during the 6 million or so years ago we have walked the planet. Of course, the precise identity of the virus invaders remains unknown. Some would have used the same genetic material as ourselves - DNA- to make up their genes. Another group of viruses termed ‘retroviruses’ almost certainly accounted for some (?many) epidemics. Retroviruses use RNA for their genetic material (RNA is a nucleotide like DNA). Retroviruses can make DNA copies of their RNA, or fragments thereof, which can be inserted into the DNA of human cells the viruses infect. We now know human genomes contain thousands of retrovirus fragments from around 30-50 families; a fossil record, if you like, of waves of ancestral viral epidemics in humans. In addition, we have inherited viral genetic material from the epidemics endured by our mammalian ancestors.

Viral genetic material contributes substantially to human evolution and genomic diversity. Sounds ominous? Yes, it can be, and we’ll come to that in a moment. But there is a good side, too. Suppose a virus introduces DNA which encodes a function useful in human evolution. That DNA may be subject to positive natural selection (provided the retrovirus infects human eggs and sperm in addition to other cells in the body, which some do). The viral-derived DNA spreads through the human population during reproduction. Just like any other useful human gene. Unlikely? No. Viral DNA encodes a protein called ‘syncytin-1’ in women. Syncytin-1 is critical for the correct functioning of the placenta during pregnancy. Another example; there are certain inserted retroviral sequences in our DNA which protect our cells from infection by further pathogenic viruses. There are numerous instances of ‘useful’ viral DNA in our genome.1 Although most genetic material of viral origin embedded in our genome is just sitting there, without function (?or is it).

It is fair to say we humans could not exist without our transposable elements of viral origin. Other viral DNA encodes transposons which jump around the genome and control the expression of human genes. Indeed perhaps 25% of human gene expression is regulated in this way.

But now, the bad side. Quietly sitting in the DNA of all of us are dormant genes called ‘oncogenes’, which, when activated, are associated with various cancers. Transposons can activate oncogenes by multiple mechanisms, including disrupting tumour suppressor genes, inducing chromosome breakages and generally causing genomic instability. The outcome is out-of-control cell proliferation, a prerequisite for cancer. Transposon-driven activation is known to occur in some twenty types of cancer.

Add a propensity for rapid mutation in retroviral-derived DNA associated with other metabolic changes in bodily function, and you have a disaster waiting to happen.

In a word, the downside of having transposable elements inserted into our DNA is that they are associated with various clinical disorders.

In some circumstances, proteins produced by transposon activation inside our cells may be perceived as ‘foreign’ by our immune system leading to autoimmune diseases in which the body attacks its own tissues.

More recently, it has been hypothesized that the accumulated volume of transposed retroviral-derived DNA exposes the body to an increased risk of malfunction as we age. A resultant inflammation in multiple organs likely exacerbates the ageing process.

So, what can clinical practice do to curb our bodies being usurped by retroviruses? Not a lot at present, apart from addressing the medical conditions the retroviruses produce.

However, transposons may be helpful to the medical profession as novel biomarkers for diagnosis, prognosis and prediction of response to therapy. Particularly those which are detected in body fluids and, therefore, easily accessible. The day may even come when transposon elements have a role as therapeutic ‘bullets’ by injection into the body.

The idea that each and every one of us has virus irreversibly embedded in our DNA is challenging enough. That the viral genes influence who we are and what might befall us is existentially daunting.

But at least when you next hear from your GP that “you’ve got a virus”, you can be confident of the diagnosis.