Sexually transmitted cancer sheds light on devil disease
Humans can't catch cancer but canines – and a marsupial – can. While it's not generally fatal for dogs it is devastating for Tasmania's iconic animal. The reason lies in its genome. Yi-Di Ng reports.
An ancient sexually transmitted cancer in dogs could shed light on the disease threatening Tasmanian devils with extinction.
Canine transmissible venereal tumour afflicts dogs worldwide, but doesn’t kill them. Instead, the disease produces benign tumours that sometimes regress naturally. By contrast, the deadly devil facial tumour disease has rampaged across Tasmania, leaving a trail of dead and diseased devils in its wake.
Dogs, unlike devils, have learned to live with their cancer. To better understand why, Elizabeth Murchison and her colleagues at the Wellcome Trust Sanger Institute in the UK sequenced the genome of the dog cancer. Their findings were published in January in the journal Science.
A Tasmanian native and long-standing researcher of devil facial tumour disease, Murchison previously sequenced the genome of the devil. She couldn’t resist the opportunity to sequence the genome of the only other known transmissible cancer. Perhaps something might be learnt that would help the Tasmanian devil?
It’s not uncommon for an infectious virus, such as the human papillomavirus, to spread between individuals and to trigger cancer. But it’s extraordinary for a cancer cell itself to spread. Not only must it colonise foreign tissue, it has to evade the new host’s formidable immune system. So far, the huge disfiguring facial tumours of the Tasmanian devil and the cauliflower-like genital tumours of dogs provide the only known examples of such transmissible cancers in nature.
Devils are notoriously aggressive, spreading the facial tumour cells when they bite each other. Their tumour is just as aggressive, spreading rapidly and killing the devils within months. Part of the problem is that the devils are so inbred, their immune systems do a poor job of recognising the invading cells as foreigners. But the tumour itself has also evolved to evade the devil’s immune defences.
The canine tumours are far less aggressive. Transmitted during mating to the partner’s genitals, the tumour barely spreads and in some cases regresses naturally. But when it comes to evading immune systems, the dog cancer is a master, spreading rampantly through far-flung dog breeds around the world.
DNA from a normal dog revealed that the tumour had accumulated
close to two million mutations.
To learn how the canine tumour was evolving, Murchison’s team sequenced the genome of tumours from dogs as far distant from each other as possible: one from an Aboriginal camp in Northern Australia, the other a cocker spaniel from Brazil. It turned out the tumour genomes were extremely similar – confirming previous findings that the tumour itself had emerged from a single rogue cell.
The team could also calculate when this first cancer cell might have lived. Comparing the DNA of the tumours with the DNA from a normal dog revealed that the tumour had accumulated close to two million mutations. Since mutations accrue at a roughly steady rate (based on cancers studied in people), the researchers estimated the dog tumour first arose about 11,000 years ago, making it the oldest known cancer in the world.
By contrast the devil tumour genome carried about 20,000 mutations, tracing the original carrier to a female that lived about 20 years ago.
We can learn lots more about that original dog tumour ancestor too. Since the dog tumour genome overwhelmingly bore the same DNA as the dog that spawned it, the researchers could decrypt the code and arrive at an identikit. It suggested a dog close to the ancient wolf-like breeds: pointy-eared, resembling a malamute with a coat that was either black or agouti (patterns of light and darker fur).
It wasn’t possible to assign the gender to the cancer-carrying dog since the cancer had only one X chromosome. It could have been a male that lost its Y chromosome or a female that lost an X. Moreover much of its genome carried two exact copies of maternal and paternal genes, suggesting inbreeding in the founder dog’s population.
Like leafing through the tattered pages of a historic manuscript, reading the genome allowed the researchers to partly piece together the story of the evolution of this extraordinary cancer, though Murchison stresses, “much of it is speculation”. 11,000 years ago, a dog in an inbred population, just like that of the Tasmanian devils, developed a cancer that sloughed off when the dogs mated. The tumour established a foothold in the inbred population, but then something changed. It developed strategies to overwhelm the immune systems of unrelated individuals allowing it to spread into populations across the planet.
Researchers are very interested in discovering what those strategies are. Whatever strategy the cancer hit on, it seems to tolerate very little change now. The DNA of the cancers in the dogs from Australia and Brazil were extremely similar. “One possibility is that the cancer is very well adapted to its niche and has been selected for genomic stability,” says Murchison.
“Now we can see what sort of mutations and genes have evolved to allow this particular cancer to persist for so long,” says Leonie Quinn, a cancer researcher at the University of Melbourne. “We finally have the opportunity to see how cancer evolves over a long period of time. We’ve never been able to because most cancers are so lethal and short-lived.”
With all this new knowledge, what does it mean for the Tasmanian devil’s plight? Quinn suspects that 11,000 years would have been sufficient time for the canine cancer to evolve into a form that spares its host. With time, the devil’s cancer may also take the same route. But time is a luxury the devils may not have.