When Anna Kukekova met the famous Siberian silver foxes, she was smitten. The behavioral geneticist at the University of Illinois in Urbana had read all about the animals, tamed so that they resembled dogs in just a few short years in mid–20th century Siberia in Russia. But when she approached them, their reactions—nuzzling, cooing, and even vying for attention like golden retrievers—was “beyond my expectation,” she says.
Kukekova immediately set aside her other work and started to search for the genetic basis of the foxes’ remarkably doglike behavior. Now, some 16 years later, she and her colleagues say they have finally found some of the keys.
“This work is really great,” says evolutionary geneticist Bridgett vonHoldt of Princeton University, who has studied the genetic differences between wolves and dogs. But she cautions that identifying the genes behind domestication is tough, because many work together in complex ways.
Kukekova first became aware of the celebrated “fox farm experiment” in 1988, when she was still a freshman at Saint Petersburg State University. In 1959, researchers took a group of wild silver foxes (a dark color mutation of the red fox) and bred only the most docile animals—those that didn’t bite when humans stuck fingers in their cages. The scientists then selected the tamest offspring of these animals and repeated the process over and over. By the eighth generation, the foxes started to seek out human company and show affection. (Today, nearly 60 years after the experiment began, some of them even enjoy belly rubs.)
In the 1960s, the scientists also bred a separate strain of foxes, selecting for aggressiveness. Over the generations, those animals were even less friendly toward humans than the other farm-raised foxes, attacking or growling at two-legged visitors as soon as they approached.
Those two strains of foxes, and a third that was neither aggressive nor tame formed the basis for Kukekova’s new study. After colleagues sequenced the silver fox genome, the team resequenced the genomes of 30 foxes—10 tame, 10 aggressive, and 10 from the “normal” group. They identified 103 genetic regions that varied significantly among the three groups. Forty-five of these overlapped with regions linked to domestication in dogs, and 30 had been previously linked to aggressive and tame behaviors in foxes. One gene from this latter set of regions stood out: SorCS1, which helps ferry proteins involved in nervous system signaling and synapse formation, assisting in memory formation and learning.
To test SorCS1’s effect on behavior, the team measured how nearly 1600 tame and aggressive foxes responded to human observers. Gathering those data took 6 years. When the researchers finally analyzed the data, they found the foxes’ behavior could be consistently linked to whatever version of the SorCS1 gene they carried, they report today in Nature Ecology & Evolution. Most of the tame foxes carried the same version of the gene, but a few carried versions common in aggressive foxes. That suggests that as the foxes undergo domestication, their genes are changing in ways that might aid in learning and memory, the researchers write.
In addition to SorCS1, the team found variations in genes related to immune response and genes that, in humans, are linked to autism, bipolar disorder, and Williams-Beuren syndrome. The latter causes “elfinlike” facial features and a friendly demeanor in humans.
No one yet knows how any of these genes function in foxes. But Constantina Theofanopoulou, a neuroscientist at the University of Barcelona in Spain who was not involved in the work, says cross-species comparisons hold promise. “The same changes that we see that provoke changes in human behavior or give rise to social deficits … are the same ones that pop up in differences in behavior and social behavior in other species.” She says future studies could use genetically engineered domesticated mice to narrow down which domesticated behaviors are linked to which genes or networks of genes.
Guojie Zhang, an evolutionary geneticist at the University of Copenhagen and the Beijing Genomics Institute and a co-author on the paper, says similar work on other species selected for tameness and aggression—such as Puerto Rico’s gentle “killer bees”—could reveal even more about behavioral changes on small time scales.
Meanwhile, the new work raises another big question: Where do we draw the line between domesticated and wild species? In domesticated animals, genetic variations are “fixed,” after natural selection weeds wild versions out of the gene pool. That’s why dogs don’t suddenly become wild if they’re not born around humans. But this isn’t the case with the tame foxes, some of which still carry “wild” versions of genes that they can pass along to their kits.
The work reinforces the idea that we should think of the wild-tame split as a spectrum, Theofanopoulou says. Once the genes of enough members of a species change in tandem, we should consider them domesticated. “This, in the end, might be what domestication is.”