STANFORD, Calif. — Slipping through trees or across snow, the wolf hasglided into legend on paws of white, gray or — in North America — evenblack. This last group owes an unexpected debt to the cousins of thedomestic dog, say Stanford researchers. In an unconventionalevolutionary twist, dogs that bred with wolves thousands of years agoceded a genetic mutation encoding dark coat color to their formerancestors. As a result, the Gray Wolf, or Canis lupus, is no longer justgray.
The effect was more than just cosmetic: the resulting black wolves,which are found nearly exclusively in North America, seem to have aselective advantage over lighter-colored wolves in forested areas. It'sa rare instance of domestic animals — in this case, probably the dogs ofthe earliest Native Americans — contributing to the genetic variabilityof their wild counterparts in a way that affects both the recipients'appearance and survival.
"We usually think of domestication as something that is carried out tobenefit humans," said genetics professor Greg Barsh, MD, PhD. "So wewere really surprised to find that domestic animals can serve as agenetic reservoir that can benefit the natural populations from whichthey were derived. It's also fascinating to think that a portion of thefirst Native American dogs, which are now extinct, may live on inwolves." Canine geneticists generally agree that North American dogstoday are all descended from European dogs.
Barsh and graduate student Tovi Anderson collaborated with, amongothers, scientists at the University of California-Los Angeles, theUniversity of Calgary, the National Park Service at Yellowstone NationalPark and the National Human Genome Research Institute to conduct theresearch, which will be published on Feb. 5 in the journal Science.Scientists from Sweden and Italy also participated in the internationaleffort.
Anderson and her collaborators compared DNA collected from 41 black,white and gray wolves in the Canadian Arctic and 224 black and graywolves in Yellowstone National Park with that of domestic dogs and grayand black coyotes. Their intention was to build on previous work in theBarsh lab that identified a mechanism controlling pigmentation in dogsthat differs from most other mammals.
"We expected this to be a short research project to confirm that wolvesand dogs shared the same genetic pathway that determines black coatcolor," said Anderson. "But the story got much more interesting when weexpanded our research and began asking about the origin of the mutationin wolves."
Dark-coated wolves are significantly more prevalent in forested areas ofthe Canadian Arctic than they are in the icy tundra (62% vs. 7% of thetotal population, respectively). Biologists have long suspected thatsomething about having black fur is particularly advantageous for thewoodland wolves, but they weren't sure what. Because black wolves graywith age, it seems that the root cause might be deeper than just coat color.
Barsh's laboratory, which has spent years studying genes affecting coatcolor and other biological pathways in mammals, discovered in 2007 thatthe gene responsible for black fur in dogs, called beta-defensin,belongs to a family of genes previously believed to be involved infighting infection. One version of the gene produces light oryellow-colored dogs and wolves; a mutant version missing threenucleotides produces black animals.
"Wildlife biologists don't really think that wolves rely much oncamouflage to protect themselves or to increase their hunting success,"said Barsh. "It's possible there is something else going on here. Forexample, the protein responsible for the coat color difference has beenimplicated, in humans, in inflammation and infection, and thereforemight give black animals an advantage that is distinct from its effecton pigmentation."
Although the "why" of this selective advantage remains a mystery, the"how" is becoming more clear. Anderson's study confirmed that theblack-coat gene shows evidence of positive selection in forest wolves.She also showed that the gene is dominant, meaning that an animal withonly one copy of the gene would still have a black coat. Ten of fourteenpups of a mating between a black wolf and a gray wolf carried the geneand were black.
She and her collaborators used a variety of genetic tests to determinethat the mutation was likely introduced into wolves by dogs sometime inthe last 10,000 to 15,000 years, about the same time the first Americanswere migrating across the Bering land bridge. These humans were probablyaccompanied by dogs, some of which carried the black-coat mutationestimated to have arisen about 50,000 years ago. The rest, as they say,was history.
"It may have been easier for dogs to interact with wolves in NorthAmerica than in Europe," said Anderson. "There was probably a higherconcentration of wolves, and the dogs, like the humans, were moremigratory."
Unfortunately, it's not yet possible to tell whether there were anyblack wolves prior to the domestication of dogs. It may be that themutation arose in the wolf population prior to the domestication of thedog somewhere between 15,000 and 40,000 years ago and then died out inthe wild. Alternatively, it may have made its first appearance in adomestic dog and never entered the wild until the Native Americansmigrated from Europe. Regardless, it's the seemingly beneficial aspectof the mutation coupled with its origin that has the researchers excited.
"This is a mutation that had been cultivated by humans in the form ofthe domestic dog for thousands of years," said Anderson. "Now we seethat it not only entered the wild population, but also is benefitingthem." The researchers speculate that the loss of the wolves' tundrahabitat may encourage the spread of the black-coat gene even further.They're interested in finding out exactly how the mutation works to helpforest wolves.
The research underscores the idea that evolution may involve otherinstances in which traits are passed in unexpected directions. "We nowknow that dogs have been the caretakers of a genetic legacy that may bevery beneficial to wolves," said Barsh. "It should lead us to think morebroadly as to how this might apply to other animals and plants."
Barsh and Anderson's Stanford collaborators include Hua Tang, PhD,assistant professor of genetics, and Sophie Candille, PhD, postdoctoralfellow in the Tang lab. The research was funded by the NationalInstitutes of Health, the National Science Foundation and the SwedishResearch Council.