Dog vaccine

The genetic mutation that makes dogs small existed in ancient wolves

Popular belief is that small dogs, such as Pomeranians and Chihuahuas, exist because once dogs were domesticated, humans wanted cute little companions. But in the newspaper Current biology on January 27, National Institutes of Health (NIH) researchers identify a genetic mutation in a growth hormone regulator gene that correlates with small body size in dogs that was present in wolves more than 50 years ago 000 years, long before domestication.

The search for this mutation had been underway at the NIH for more than a decade, but researchers didn’t find it until Jocelyn Plassais (@JocelynPlassais), a postdoc in the lab of geneticist Elaine Ostrander , suggests that they look for sequences around the gene that were placed upside down and confirm if there were any in other canids and in ancient DNA. With this approach, their team found an inverse form of the insulin-like growth factor 1 (IGF1) gene with variants correlated to dog body size. “We looked at 200 breeds, and it held up well,” says Ostrander.

The researchers then collaborated with evolutionary biologists Greger Larson (@Greger_Larson) from Oxford University and Laurent Franz from Ludwig Maximilian University to examine ancient wolf DNA and see when the IGF-1 mutation appeared for the first time. Scientists have theorized that dogs started out large and got smaller around 20,000 years ago when they were domesticated, but this discovery presents the possibility of a new evolutionary narrative.

Indeed, when the team looked at the DNA of a 54,000-year-old Siberian wolf (Canis lupus campestris) they discovered that he also had the growth hormone mutation. “It’s as if nature kept it in its back pocket for tens of thousands of years until it was needed,” says Ostrander.

The discovery applies not only to dogs and wolves, but also to coyotes, jackals, African hunting dogs and other members of the animal family called canids. “It’s so tied to canine domestication and body size, and things that we think are very modern are actually very old,” says Ostrander.

Ostrander and his team plan to continue studying the genes that regulate body size in dogs. “One of the things that’s kind of cool about dogs is that because they’ve evolved so recently, there aren’t a lot of body size genes,” she says. Canids have only 25 known genes that regulate body size, compared to several hundred in humans. “I really want to understand the whole continuum — from Chihuahuas to Great Danes,” says Ostrander.

This work was supported by funding from the Intramural Program of the National Human Genome Research Institute.

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