For nearly 60 years, Russian scientists have bred foxes to be tame—or aggressive. A new study looking at the genomes of the two groups shows that the experiment has changed the animals’ DNA in surprising ways. The research has relevance for understanding social behavior across animals and even humans.

It took a while to get to here. In 1959, a man named Dmitri Belyaev began an experiment designed to understand how dogs became domesticated. Belyaev and other biologists believed that domestic dogs were descended from wolves, but did not yet know how all the anatomical, physiological, and behavioral differences between the two animals could arise.

But Belyaev had a hunch. He suspected that the key component was the dog's tameness. Perhaps, he hypothesized, the biological changes in domesticated animals—white spots, curled tails, floppy ears, shortened skulls—were the result of an evolutionary selection process over behavioral traits rather than anatomical ones.

Fearful and Friendly

Belyaev believed that by breeding the friendliest foxes with each other, perhaps he could domesticate them, artificially mimicking the millennia-long process through which wolves became dogs. He bought up a group of silver foxes from a Canadian fur farm and got to work at his lab in the Soviet Union. (See also: These foxes ‘grow’ their own gardens.)

Belyaev would eventually prove himself right. Breeding the least fearful foxes with each other resulted not only in animals that were eager to seek out a social connection with humans, but also in animals that displayed the suite of anatomical features associated with domestication: those characteristic white spots, curly tails, floppy ears, and so on.

PLAYFUL, ELUSIVE FOXES TOOK YEARS TO FILM

The entire collection of modifications associated with domestication could be brought about simply by breeding foxes according to their response when approached by a human. Would they approach the experimenter with curiosity and permit physical contact? Or would they back away, hissing and yelping out of fear?

Belyaev died in 1985, but the experiment continues today. Researchers have bred more than 40 generations of friendly and aggressive foxes. And now, for the first time, they have a fully sequenced fox genome to help understand the genetics that underlie the transition from wild to tame, as described in a study published today in the journal Nature Ecology and Evolution.

View Images The Russian fox breeding experiment produced docile animals, much as selective breeding over millennia produce domestic dogs. Photograph by Darya Shepeleva

The researchers sequenced the genes of 10 foxes from the aggressive and tame populations, and assembled a complete genome of the silver fox (Vulpes vulpes). This has and will continue to allow them to find genetic differences that could underlie different aspects of domestication, says University of Illinois biologist Anna Kukekova, who led the study.

Until now, researchers have had to rely on the domestic dog genome as a reference. But while wolves and foxes diverged only 10 million years ago, dogs and foxes have dramatically different lifestyles. (Related: Why are dogs so friendly? Science has an answer.)

Genetic Secrets

Kukekova and her colleagues zeroed in on one of the 103 genomic regions that differed between the tame and aggressive foxes. This analysis found that the tamest foxes had a version of a gene called SorCS1 that did not appear in either the aggressive or conventionally-bred foxes. Meanwhile, a different version of SorCS1 most common in aggressive foxes was incredibly uncommon in the other groups.

There was no prior reason to suspect that SorCS1 was associated with social behavior. "It was known to be associated with autism and Alzheimer's disease [in humans]," says Kukekova. And a mouse study recently found that SorCS1 is involved in synapse formation and neuronal signaling. This paves the way for understanding how the gene might affect social behavior, she says.

View Images Breeding foxes to be docile has also produced anatomical changes associated with domestication, such as floppy ears. Photograph by Darya Shepeleva

Domesticated animals experience less stress than wild creatures when confronted with unfamiliar people or objects, and the paper turned up genes that may be involved in this behavioral difference, which is tied to a blunted response in the hypothalamic-pituitary-adrenal, or HPA, axis. This series of biological structures form a connection between the brain and endocrine systems in the body that activates in response to stress.

The study also turned up one genomic region of interest that has been associated with domestication in dogs and with Williams-Beuren syndrome in humans, a genetic condition associated with exceptionally friendly behavior. Surprisingly, though, the "Williams-Beuren region" shows up in the aggressive foxes, rather than the tame ones.