In a world first, scientists have demonstrated that a particular type of DNA can shuttle between cells in an animal, a finding that will rewrite textbook science. During their study, the team observed that DNA from a mouse's second genome, or mitochondrial DNA, could be transferred from healthy tissue to tumor cells in mice, promoting cancer growth and spread.
Not only could these important findings help further our understanding of cancer and other diseases, but they raise the tantalizing possibility that one day, it might be possible to replace faulty, disease-causing genes with synthetic, custom-designed mitochondrial DNA in a bid to fight a wide variety of illnesses. The work has been published in Cell Metabolism.
Many of you will be familiar with the nucleus, the membrane-bound structure within our cells that contains our DNA, the material that provides the instructions for our characteristics, or traits. But did you know that you also have a second genome? Tiny, sausage-shaped structures within our cells called mitochondria have their own DNA, called mtDNA.
This genome is much smaller than the human nuclear genome, containing 37 genes as opposed to around 20,000. All of these genes are essential to the normal function of the mitochondria, which act as powerhouses for our cells, converting energy from food into a form that our cells can use. Because mitochondria lack an efficient proofreading system to check for mistakes in DNA replication, mtDNA is prone to mutations which can sometimes cause disease. The effects of these mutations are most evident in energy-hungry tissues such as the muscles and brain.
Since these energy factories are so important for the functioning of a cell, scientists wondered whether removing mtDNA from cancerous cells could thwart the development of tumors. To test this idea, researchers from the Malaghan Institute in New Zealand generated a mtDNA-deficient breast tumor cell line, which was found to show delayed tumor growth in mice. However, a month or so later, tumors eventually started sprouting in the mice.
“Initially we thought the cells had learned to grow without needing mitochondrial DNA,” lead researcher Professor Berridge said in a news release. But after an esteemed scientist asked if they had investigated whether the cells contained mtDNA, the researchers decided to find out. It didn’t take long to confirm the presence of mtDNA in the tumor cells, but it took some digging to work out where it had come from.
After extensive molecular and protein analyses, they eventually established that the DNA had been obtained from non-tumor cells. Furthermore, DNA sequence analysis revealed that the transferred DNA was distinct from that of the original tumor, but identical to surrounding healthy tissue.
“Our findings overturn the dogma that genes of higher organisms are usually constrained within cells except during reproduction,” said Berridge. “It may be that mitochondrial gene transfer between different cells is actually quite a common biological occurrence.”
The researchers aren’t sure at this stage whether this is important in the development of tumors, but they would like to continue the work to see if this process occurs more widely in the body. They also believe this work could open up new research fields where scientists attempt to replace faulty, disease-causing mtDNA with custom synthetic DNA.