A Canine Gene Mutation Associated With Small Body Size Arose Over 53,000 Years Ago

Researchers have assembled a catalog of 1,431 genomes, including ancient canids, modern pedigree dogs and wild canids, in a search for genetic variants passed down from ancient dogs to modern dogs. They have identified an ancient mutation in a human-selected growth hormone regulator gene that contributes a significant portion of the body size of modern dogs.

Plassais et al. identified an ancient mutation in IGF1 locus which contributes to a significant portion of body size in modern dogs. Illustration by John James Audubon and John Bachman.

“Domestic dogs (Canis lupus familiaris) are the most size-variable mammal species on Earth, showing a 40-fold size difference between races,” said lead author Dr. Jocelyn Plassais, postdoctoral researcher at the National Institute for Research on Human Genome from the National Institutes of Health, and colleagues. .

“Although dogs of varying size are found in the archaeological record, the most dramatic changes in body size are the result of selection over the past two centuries, as dog breeders have selected and propagated phenotypic extremes throughout the world. within closed breeding populations.

The search for the body-size-associated mutation had been underway at the National Institutes of Health for more than a decade, but the researchers couldn’t find it until Dr. Plassais suggested they search for sequences. around the gene that were positioned upside down and confirms whether some were present in other canids and in ancient DNA.

With this approach, scientists found an inverse form of insulin-like growth factor 1 (IGF1) gene with variants correlated to dog body size.

“We looked at 200 breeds, and it held up well,” said lead author Dr. Elaine Ostrander, a geneticist at the National Human Genome Research Institute.

The <a class=canid ancestor was probably small and carried the candidate SNP C allele, rs22397284. The large allele appeared some time before 53,000 years before present and generated larger animals (Canis lupus). The small ancestral allele continues to exist in the gray wolf population, although at a low frequency. Around 15,000 years before present, canine domestication probably began with large, wolf-like dogs. Soon after, human selection of small canids with the ancestral C allele led to a preponderance of modern small domestic breeds. The gray arrow reflects the actual hybridization observed between coyotes and wolves in eastern America. Image credit: Plassais et al., doi: 10.1016/j.cub.2021.12.036.” data-src=”http://cdn.sci-news.com/images/2022/01/image_10500-Canine-Sizes.jpg” width=”580″ height=”373″/>

The canid ancestor was probably small and carried the candidate SNP C allele, rs22397284. The large allele appeared some time before 53,000 years before present and generated larger animals (Canis lupus). The small ancestral allele continues to exist in the gray wolf population, although at a low frequency. Around 15,000 years before present, canine domestication probably began with large, wolf-like dogs. Soon after, human selection of small canids with the ancestral C allele led to a preponderance of modern small domestic breeds. The gray arrow reflects the actual hybridization observed between coyotes and wolves in eastern America. Image credit: Plassais et al., doi:10.1016/j.cub.2021.12.036.

The authors then examined the ancient wolf DNA to 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 Dr. Plassais, Dr. Ostrander and their co-authors looked at the DNA of a 54,000 year old steppe 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,” Dr Ostrander said.

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,” Dr Ostrander said.

The team now plans to continue studying the genes that regulate body size in dogs.

“One of the things that’s pretty cool about dogs is that because they’ve evolved so recently, there aren’t a lot of body-size genes,” Dr. Ostrander said.

“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.”

The study appears in the journal Current biology.

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Jocelyne Plassais et al. 2022. Natural and human selection of a single noncoding body size variant in ancient and modern canids. Current biology 32:1-9; doi:10.1016/j.cub.2021.12.036


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