Ancient Dog DNA Reveals Close Relationship with Contagious Cancer

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Ancient Dog DNA Reveals Close Relationship with Contagious Cancer

By analyzing dog DNA from archaeological remains, researchers last week pinned down the evolutionary history of domesticated dogs in North America. Dogs are thought to have first populated the Americas alongside humans via the Bering Land Bridge more than 10,000 years ago. These early arrivals disappeared following the introduction of European breeds, leaving little genetic trace among modern dogs, according to the new study. But the researchers found a relative of America’s original dogs that persists in a bizarre form: a sexually transmitted cancer descended from the tumor of single dog that lived thousands of years ago.

Dogs played a key role in ancient Native American societies, according to Laurent Frantz, a geneticist at Queen Mary University of London and a co-author of the study. “These cultures didn’t have access to any other domestic animals, so dogs were really important,” says Frantz, who notes dogs may have aided in transportation and hunting. Both the origin and fate of these ancient American dogs have been hotly debated. So his team set out to establish where these dogs came from and what happened to them following the arrival of European breeds.

The researchers sequenced DNA collected from the remains of 71 dogs between 1,000 and 10,000 years old found at archeological sites in North America and Siberia. The genomes of the ancient American dogs were similar to those of the ancient Siberian dogs and bore little resemblance to those of modern North American ones. Curiously, the scientists found the ancient American dog DNA almost perfectly matched that found in canine transmissible venereal tumor (CTVT), a contagious cancer that afflicts dogs. The researchers concluded the ancient American dogs were close relatives of the dog that first suffered CTVT, whose DNA is now preserved in the tumors of millions of dogs worldwide. “It is a genome frozen in time,” Frantz says.

Although cancer is common across the animal kingdom, the disease generally is not infectious like the flu. One animal’s immune system typically recognizes and kills cancer cells from another animal, says Máire Ní Leathlobhair, a cancer biologist at the University of Cambridge and a co-lead author of the study, which was published on Thursday in Science. But CTVT is an exception whose virulent origin has perplexed scientists.

Ní Leathlobhair’s team determined CTVT is a much younger disease than previously thought. They extrapolated mutation rates in CTVT DNA over time, and discovered the “founder” dog, whose cells mutated into the initial CTVT tumor, lived within the last 8,225 years—3,000 years later than prior estimates. The newly established timing, combined with the similarity between CTVT and ancient American dog DNA, means the CTVT founder could have been a domestic dog in North America. But the founder’s exact location is far from settled, even among the study’s co-authors.

“That was a little controversy we had among the group,” Ní Leathlobhair says, adding CTVT contains traces of DNA from coyotes, which are only found in North America. But prior studies have shown the CTVT strain currently found in the Americas was introduced within the last 500 years. She says the simplest explanation is the original CTVT tumor arose in a Siberian dog, a close relative of the ancient American dogs, and from there spread throughout the world. Regarding the coyote DNA in CTVT, she notes it “wouldn’t be too surprising” if a small number of North American coyotes traveled over the Bering Land Bridge to Siberia and mated with local dogs. “We know there was movement back and forth of people,” she says. “We think the same might be true of dogs.” Wild canids like coyotes may have followed suit, she adds. Alternatively, CTVT could have arisen in an ancient North American dog, spread into Siberia and beyond, then reentered the Americas just within the last 500 years. Ní Leathlobhair hopes to address this question in future research.

“This is an exciting and very well done study,” says Elaine Ostrander, a geneticist at the National Institutes of Health who was not involved with the work. She adds that the sequencing of DNA from nuclei of the ancient dogs’ cells sets this research apart, because nuclear DNA is rich with information about both maternal and paternal ancestry. Prior studies on ancient American dogs have been limited to DNA from cellular components called mitochondria, which is preserved better than nuclear DNA but only encodes information about the maternal line. “Using the nuclear DNA sequence to help fill in some of the missing pieces is certainly not something that’s been done before,” Ostrander says. She also notes this is the first study of ancient American dogs to include data about CTVT, which is the “oldest propagated cell line in the world.”

Besides CTVT, scientists know of very few contagious cancers. The first documented case in Tasmanian devils broke one of the “axioms of cancer science”—that the ailment cannot jump between individuals, Ní Leathlobhair says. Devil facial tumor disease, spread by the animals’ propensity for biting one another’s faces, now threatens the devils with extinction. A study published in 2016 revealed a cancer that can leap not only among individuals of the same species but also among related species of mussels and clams.

In exceptional cases cancer may be transferred from one human to another. Through the 1950’s and ’60’s Chester Southam, an oncologist at Memorial Sloan Kettering Cancer Center, experimentally injected cancer cells into more than 300 people, often without properly informing them. Some subjects, which included prison inmates, developed tumors from the injected cells. (Southam was never prosecuted and was later elected president of the American Association for Cancer Research.) In two more recent instances medical staff accidentally punctured themselves while working with cancer cells and later developed tumors. Most other cases of cancer transmission between humans involve organ transplants containing malignancies or mother-to-fetus transmission. A study in 2015 documented a man with HIV, which suppresses the immune system, developing cancer from malignant cells of a parasitic tapeworm. In general, however, people need not worry about “catching” cancer, Ní Leathlobhair says. But the story is different for dogs, because CTVT afflicts canines on every continent but Antarctica.

Frantz says CTVT’s ancestry was the study’s “biggest surprise,” although his team also answered a broader set of questions about the history of ancient American dogs. First, their genomic evidence indicates domesticated dogs traveled with people from Siberia to North America, eliminating the possibility Native Americans tamed wolves after arriving on the continent. Second, Frantz says their study provides “definite proof” European dog breeds almost completely replaced ancient American breeds following colonization. The researchers found no traces of ancient American dog ancestry in the genetic makeup of modern American dogs.

With these questions settled, Frantz says there is more to learn about how the European dogs replaced the ancient American ones. Social factors are commonly offered as an explanation, he says, including European colonists’ preference for their own dogs for hunting and herding. He believes, however, there is more to the story than cultural practices. “I find this explanation alone to be not fully satisfying,” he says. “Such a drastic replacement calls for something a bit more catastrophic, like an infectious disease.” One suspect is CTVT—the genetic relationship between the tumor and the ancient American dogs could have made them particularly susceptible to infection. “This cancer may have played a role in the demise of these dogs,” he says. Until the team finds direct evidence, he notes the idea that CTVT contributed to the disappearance of ancient American dogs is “purely speculative.” Still, he says, “I think it’s a fascinating possibility.”

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