Best-friend genetics

DOGS have long been man’s closest animal companion. The story of how they accompanied traders and settlers to every corner of the globe has now been pieced together in an unusual way by a group studying a unique genetic tag associated with a canine cancer. And in the process, this has turned up surprising new evidence about how cancer cells survive.

Transmissible cancers are rare. One of them, canine transmissible venereal tumour (CTVT), spreads between dogs through the transfer of living cells during mating. The disease, which usually appears as genital tumours in both male and female dogs, is believed to have originated in a single dog some 11,000 years ago and survived by spreading to other dogs. It is now found in dogs worldwide.

Since that founder dog first spawned CTVT, however, the disease has changed its genetic nature, according to Andrea Strakova, Máire Ní Leathlobhair and Elizabeth Murchison of the University of Cambridge’s Department of Veterinary Medicine and an international team of colleagues. They looked at the DNA of mitochondria in 449 tumours in dogs from 39 countries. Mitochondria are units within cells that act as power plants, turning the energy contained in sugar into a form of fuel which a cell can use. Mitochondria have their own genome, which is likely to be a hangover from a time when they may have existed as free-living organisms. Previous studies have shown that mitochondrial DNA has been able to transfer from body cells in infected dogs into the cells in their tumours, and hence to the tumours of dogs that were subsequently infected.

As the group report in eLife, they found evidence of the cancer having “stolen” mitochondrial DNA from the cells of its host on at least five occasions during the long history of the disease. This may well have been done to help the tumour survive, says Ms Strakova. By mapping the points at which mitochondrial DNA made the transfer it was possible to work out how the tumours are related to each other.

Of the five main branches of the family tree (known as “clades”) which the researchers came up with, the oldest arose 1,000-2,000 years ago, probably in India, where the clade still persists. One of the most common clades spread from Russia or China around 1,000 years ago, but did not arrive in the Americas until within the last 500 years, suggesting it was taken there by European colonialists. Contemporary art shows conquistadors used dogs both for protection and as a source of food. The disease arrived in Australia around the turn of the 20th century, most likely among dogs accompanying European settlers.

Yet the study also found an exceptional dog in Nicaragua in which its tumour had not just mingled with some mitochondrial DNA from its canine host but actually spliced the two sequences together. This so-called “recombination” of DNA in mitochondria is extremely unusual. It could be happening on a much wider scale, the researchers believe, perhaps even in human cancers, where it would be much more difficult to detect because the tumour’s mitochondrial DNA is likely to be very similar to the mitochondrial DNA in the patient’s normal cells. It is not yet known what the significance of mitochondrial DNA recombination in cancer could be. But it might be that the genetic changes it bestows somehow help cancer cells. If so, blocking the process could provide another way to fight the disease. That would be one more debt man owes to his dogs.