Charles Darwin once wrote that there was no animal more difficult to tame than a young wild rabbit, and yet no animal tamer than a young domesticated one. Now modern science is backing him up. At last week’s Biology of Genomes meeting here, researchers reported that domesticated rabbits, instead of arising through changes in just one or two genes, have many subtle genetic shifts distinguishing them from wild rabbits. The same likely holds true for other animals, predicts the Uppsala University team that helped conduct the rabbit study.

“The message here is that there’s no [single] domestication gene,” says Peter Andolfatto, an evolutionary geneticist at Princeton University.

Researchers have probed the history of sheep, dogs, horses, and other species, looking for DNA that helped make their wild ancestors more accommodating to people. “People believe that there must be a speciation gene,” Andolfatto says. “It’s almost a paradigm.”

Yet, while scientists have identified several genes that confer specific traits in these species that humans have bred or selected for, such as a special gait in horses, these “are not critical for domestication,” says Leif Andersson, a geneticist at Uppsala University in Sweden. Such genes have been hard to pinpoint, in part because most animals were domesticated thousands of years ago, so it’s difficult to know for sure who the true ancestors were and if they are still around for DNA comparisons.

Rabbits are a different story. People domesticated these animals relatively recently. About 1400 years ago, after a pope declared that they were “fish” that could be eaten during Lent, monks and others brought wild rabbits into the fold. Until then, the animals lived only in Spain, Portugal, and southern France. They still run wild there today, so the researchers had easy access to the domesticated rabbit’s ancestors.

The team collected and sequenced DNA from 14 wild rabbit populations and from six domestic breeds. It found that the rabbit genome is quite variable from one individual to the next, much more so than in humans. Yet not enough time had passed for the domestic rabbit to evolve very many consistent differences from the wild ancestor, and no gene stood out as key to domestication, reported Andersson’s colleague, Nima Rafati, at the meeting. “We did not find any evidence for [key] domestication genes,” he concluded. “We propose that they may not exist.”

Instead, there were thousands of places in the genome where the frequency of certain versions of genes and other DNA differed between wild and domesticated rabbits. Many of these places were in regulatory DNA that helps control gene activity.

That DNA tended to be associated with brain and nerve cell development, Rafati said. For example, domestication had seemingly altered 13 places near a gene called SOX2, which helps maintain cells destined to become part of the nervous system.

The conclusion of the rabbit genome study “goes against the grain,” Andolfatto says. “The message coming from the rabbit is that it’s just a large number of small changes.” But the results are in line with what Alex Cagan, a graduate student at the Max Planck Institute for Evolutionary Anthropology who was not involved with the rabbit work, also reported at the meeting about his rats, which he is breeding to be tamer or more aggressive. He, too, finds a broad number of places in the DNA are changing, many of which are important in the nervous system or in early development.