This genetic mutation helped scientists track the evolution of domestic dogs

Surapol Manee
·4 min read

On appearances alone, it may be hard to believe dogs like fluffy Pomeranians or spritely Chihuahuas really are descended from wolves. But new research both illuminates and solidifies this relationship, while providing a new explanation as to why owners are even able to pick teacup poodles and short-snouted Shih Tzus out of the pack.

Domestic dogs come in more sizes than any other mammal species on Earth. This is a result of human preference and selective breeding — but this wide range of sizes is foundationally possible because of a newly discovered genetic mutation. This mutation corresponds to small body size and it emerged in wolves before they were domesticated.

This discovery was announced Wednesday in the journal Current Biology.

“I think most people don’t realize dogs were domesticated only 20,000 years ago, which evolutionarily is a teeny part of a teeny drop in the bucket,” said lead author Elaine Ostrander, chief and distinguished senior investigator of cancer genetics and comparative genomics branch at the National Institutes of Health.

“Bringing ancient wolf and dog DNA together is so exciting,” Ostrander said. “You can see all of this variation running around in a dog park and say ‘I know what your DNA looked like 50,000 years ago.’”

While humans have several hundred genes that regulate body size, domestic dogs have just 20 body-size genes. The strongest is an insulin-like growth factor 1 (IGF-1), which controls 15 percent of body size variation across dogs. For nearly a decade, Ostrander and colleagues have searched for a mutation related to IGF-1 — a genetic signal they could find across canids, the group of mammals that include wolves, coyotes and domestic dogs.

It finally revealed itself once the team examined the noncoding strand of the gene, or antisense. An analysis of 1,431 genome sequences spanning 13 species of both ancestral and modern canids revealed a variant, or gene mutation, within the antisense that interacts with the IGF-1 gene. This was “really the key that unlocked everything,” Ostrander said.

This mutation creates a point of variation, resulting in what the team describes as either a small allele or a large allele. Alleles are alternative forms of genes that arise by mutation and are found at the same place on a chromosome. Subsequently, this mutation can explain body size differences across ancient and modern canids.

These alleles have conferred “morphological plasticity” to modern dogs; because both alleles are circulating within the global dog population, people can selectively breed dogs of widely different sizes. For example, there are three sizes of schnauzers: toy, miniature and standard. The toy and miniature schnauzers analyzed in the study contained the small allele, while the giant schnauzers contained the large allele.

An analysis of ancient canids also revealed the large allele was more often found in wolves excavated from northern latitude sites, while the small allele was more frequently identified in wolves excavated from southern latitude sites — mostly from the Mediterranean region. This jibes with a concept known as Bergmann’s rule, which, simplified, states that being big is more advantageous if one lives in a northern climate.

The study suggests this large allele most likely emerged in wolves more than 53,000 years ago, likely due to natural selection. These wolves lived during the Pleistocene, also known as “the ice age.” Lower temperatures likely caused this allele to become a fixed feature of northern wolves, while the small allele persisted in wolves living in southern, warmer regions.

This makes the small allele the ancestral allele — a trait that stems from the common ancestor of canids. However, “what it was doing before 53,000 years ago, we have no idea,” Ostrander said. “We don’t know why nature maintained it.”

These findings may bring pet owners closer to understanding man’s best friend, but the primary purpose of the study is to improve human health. The 25 genes related to body size in domestic dogs are found in humans, and these genes can be responsible for diseases like cancer.

“We look at where the mutations are, what’s tolerated and not tolerated, and what’s going on around it,” Ostrander said. “Then we look at human mutations and we can begin to put together a story of what parts of the gene are critical and what parts are responsible for poor health.”

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