mutation explains canine size range
From Chihuahuas to Great Danes, dogs differ more in size than any other mammal species on the planet. A mutation behind such variation has been attributed to an unexpected source: ancient wolves.1.
The mutation is near a gene called IGF1, which researchers reported 15 years ago as having a major role in height variation in domestic dogs. It was the first of about two dozen such genes identified. But efforts to identify the gene variant responsible had been unsuccessful.
“IGF1 was a thorn in our side,” says Elaine Ostrander, a geneticist at the US National Human Genome Research Institute in Bethesda, Maryland, who led the 2007 study that first identified IGF1role of in dog size2as well as the study of January 27 Current biology which now completes the quest.
Ancient dogs, domesticated from wolves over the past 30,000 years, differed to some extent in size. But today’s extreme size differences – the largest breeds are up to 40 times larger than the smallest – arose in the last 200 years, when humans established modern breeds.
Ostrander and his colleagues, including geneticist Jocelyn Plassais of INSERM-University of Rennes, France, analyzed the genomes of more than 1,400 canids, including ancient dogs, wolves, coyotes and 230 modern dog breeds.
When they compared the variation in the region around the IGF1 gene with body size in dogs and wild canids, one variant stood out. It is found in a stretch of DNA that codes for a molecule called long non-coding RNA, which is involved in controlling levels of the powerful growth hormone protein IGF1.
The researchers identified two versions, or alleles, of the variant. Across all breeds, dogs with two copies of an allele tended to weigh less than 15 kilograms, while two copies of the other version were more common in dogs weighing more than 25 kilograms. Dogs with one copy of each allele tended to be intermediate in size, Ostrander says. Dogs with two copies of the large allele also had higher levels of IGF1 protein in their blood, compared to those with two copies of the “small” allele.
When the researchers looked at the genomes of other canids, they found a similar relationship. “It wasn’t just a dog story. It was a wolf story and a fox story and a coyote story and everything. It was on a canine scale,” says Ostrander.
The researchers believe that the allele linked to small bodies is, evolutionarily, much older than the large-body version. The coyotes, jackals, foxes and most other canines they analyzed had two copies of the “small” version, suggesting that this version was present in a common ancestor of these animals.
It is not known when the large-body allele evolved. Researchers have found that an ancient wolf that lived in Siberia around 53,000 years ago carried a copy of this version. Other ancient wolves and modern gray wolves tend to have two, suggesting that the large-bodied allele could have been beneficial to wolves.
According to Robert Wayne, an evolutionary biologist at the University of California, Los Angeles, the prevailing view among scientists was that short stature was likely linked to relatively new genetic changes potentially unique to domestic dogs. “It upsets the whole story. That’s the wonderful thing about it.
The study could be a sign that dogs were domesticated from smaller wolves, different from current gray wolf populations, says Elinor Karlsson, a geneticist at Chan Medical School at the University of Massachusetts Worcester. “We don’t even know what the wolves that led to the dogs looked like,” she said.
The researchers also warn that the dog’s size story is far from complete. Plassais wants to determine how the variants influence levels of the IGF1 protein. And variation is not the only determinant of size in dogs: IGF1 gene itself accounts for about 15% of the variation between races.
“We’re not talking about a mutation that makes a wolf the size of a Chihuahua,” Karlsson explains. “We’re talking about one of many mutations that tends to make you a bit smaller.”