We know that the difference between Cabernet-Sauvignon and Chardonnay is red versus white wine grapes. But how did this change occur? It was a jumping gene that induced red grapes to produce a white-skinned variety by changing the sequence of one of its genes. It turns out that the same DNA elements that caused this change also exist in humans.

 Jumping genes have likely been in our genome for thousands of years. They are quiet residents, bringing genomic diversity and evolution to thousands of species. However, they can also be the bearers of bad news. Occasionally, it’s the sudden movement of these elements around our genome that can be one of the leading causes of disease.

Two glasses of red and white wine on barrel in the cellar
Jumping genes caused red grapes to produce white-skinned ones, giving us the red and white varieties we enjoy today. The same DNA elements that caused this change also exist in humans and are linked to both health and disease.

Where do jumping genes come from?

The human genome is huge. In fact, putting all the DNA strands from your body end-to-end would reach the end of the solar system. The genome is so intriguing that, in 2001, the ambitious Human Genome Project was launched, aiming to sequence and understand what every gene of the human body was doing. Upon its completion in 2003, the Human Genome Project discovered that despite the huge size of the human genome, the genes that code for a protein and that therefore have a functional role in forming the cell’s identity was only a tiny 2%! The remaining 98% was a mystery, and so it was termed the Dark Genome.

DNA in every living organism is made up of just four chemical structures, called nucleic acids, that scientists abbreviated A, T, C, G. Individually, the chemicals have no purpose, but when attached together into long strands of DNA called chromosomes, they provide the instructions coding for every cell’s identity in the entire body. Imagine these four nucleic acids each represent letters in the alphabet. The letters alone do not carry any meaning. However when these letters are combined into words and sentences to make the full-length DNA, they begin to make sense. Using state-of-art sequencing technology, the Human Genome Project aimed to read all the letters, end-to-end, of the human DNA book. The Human Genome Project discovered that most of the DNA in the Dark Genome was not only extremely challenging to sequence, it was also almost impossible to interpret what function this DNA was having in the cells. 

Launched from these findings was the Encyclopaedia of DNA Elements (ENCODE) which aimed to determine exactly what this mysterious Dark Genome was doing in our cells.  

One of the major findings of the ENCODE project was that a vast contributor of the Dark Genome was a unique type of element called a transposon, or a jumping gene. In fact, these jumping genes had already been described by the Nobel prize winner Barbara McClintock 50 years earlier, although her theories had been under some scepticism during that time! 

Transposons are exceptional. They have the exclusive ability to move around the genome and relocate their DNA sequence. For many types of transposon, this movement occurs through an intermediate, highly specialised molecule. Through either a “copy-and-paste” or “cut-and-paste” like strategy, depending on the type of transposon, the jumping gene can copy its sequence back into the genome at an alternative location. Imagine a single sentence in a book, copied and pasted thousands of times again and again through the book. Using your eyes, it would be impossible to perfectly guess how many times the sentence is copied, and from which part of the book a single sentence originated. The sequencing machine is no better at this challenge! It is easy to see how this sequence could be considered junk.

A blue keyboard key with text copy / paste
Jumping genes can copy and paste themselves around the genome, which drives genomic diversity but can also cause disease.

Transposons however are far from junk. The ability of transposons to copy themselves around the genome can be highly beneficial, bringing diversity and boosting evolution. It was the mobility of transposons that likely drove the activity of genes required for the earliest steps of normal embryonic development. They also likely played a role in the evolution of the placenta, a temporary organ unique to mammalian embryonic development.

But they can also bring chaos. 

They were first discovered to be the cause of illness in two unconnected individuals who both had a severe blood disease in 1988. Researchers found that a transposon had jumped directly into the middle of a coagulation gene called “F8”. Imagine as if one sentence, the transposon, had inserted itself into the middle of another sentence, the gene, in the DNA book. The words no longer make sense. It’s thought that approximately half of human cancers may have been induced by a transposon changing the DNA sentence of a healthy protein coding gene into something nonsensical. Often these healthy protein coding genes are a type of gene called a “tumor suppressor.” When a transposon inserts into this type of gene, it deactivates its usual function, switching it from being a suppressor to allowing tumor development. Studies of the gene “APC”, which is commonly affected in colon cancers, found exactly this; a transposon had jumped into the middle of this gene and disrupted its normal function. 

On the flip side, some transposon types have even been shown to prevent cancer development. A recent study using leukaemia cells, found that the activity of transposons actually suppressed acute myeloid leukemia advancement. When the scientists blocked transposon activity, they found that the progression of the leukaemia, and so potentially patient prognosis, was actually worse.

New therapies and treatments for diseases such as cancer could be achieved by understanding and interpreting the benefits, activity and mechanisms of the Dark Genome, and the ability of transposons contained within this DNA to move around. It will also mean learning more about the role of transposons in genetic diseases and fertility. Scientists currently speculate that the extent of transposon activity in female eggs may be used by the ovary as a method of quality control.

To make the most effective treatments, we need to be able to read the human genome book in more detail. In 2021, a game-changing not-yet-peer-reviewed sequencing study was released, adding an astounding 200 million nucleic acids, containing 115 new genes, to the data from the Human Genome Project, using the most modern and contemporary state-of-the-art DNA sequencing strategies. Now, instead of sequencing single letters at a time, we are able to sequence whole paragraphs or pages of the DNA book in one go, enabling scientists to make more accurate guesses about the function and origin of the repetitive sequence contained within the Dark Genome. 

What we can be sure of however, is that junk DNA is far from junk. In fact, your junk DNA may contribute some of the most important DNA sequences your cells could ever ask for. We are just beginning to learn why.