When humans domesticated wild rabbits and turned them into pet store favorites, they also changed their genome, a study has found.

The change has been dramatic; while a pet rabbit will contentedly sit in a human lap to be petted, wild rabbits remain incredibly timid animals, running away from any fox, hawk -- or human.

Looking to find the genetic foundation for such a stark difference in behavior, researchers at Uppsala University in Sweden, working with international colleagues, compared genomes of domesticated rabbits with the genomes of their wild counterparts.

The domestication of rabbits happened much more recently than that of cattle, sheep, pigs and dogs, which happened between about 15,000 and 9,000 years ago.

Monks in monasteries in the south of France first domesticated rabbits around 1,400 years ago.

The Uppsala researchers wanted to find out if domestication of rabbits involved drastic changes to a few key genes or more subtle changes in a large number of them.

The discovered that no genes had been completely turned off, one possibility that could have led to a reduction in the animals' fear of humans.

"Gene loss has not played a prominent role during rabbit domestication," says study leader Leif Andersson.

Rather, the researches report in the journal Science, small pre-existing genetic variations -- sometimes just one letter of DNA code -- started to become more common in the animals as they became domesticated.

These variations generally didn't affect the genes themselves, but rather acted on the genome's regulatory regions, which are in control of whether genes are turned on or off.

"Wild and domestic rabbits do not differ so much in actual protein sequences, but in how gene and protein expression is regulated," says Andersson.

Among the genes particularly targeted during domestication were those involved in rabbits' brains and nervous systems.

That's to be expected, Andersson says, because the differences between domestic and wild rabbits are almost all behavioral, while physical differences are slight.

"This pattern contrasts with the large-effect genetic changes that are typically associated with striking differences in the size or appearance of diverse domestic dog breeds, for example," says study co-author Jeffrey Good from the University of Montana. "These results are exciting because they shed light on what types of genetic modifications are likely to be important during the early stages of domestication."

Domestication of rabbits was made easier because the wild variety is a highly polymorphic species that already possesses many of gene variants selectively enhanced during domestication, the researchers say.

That is likely to have been the case with most domesticated species, they say.

"We predict that a similar process has occurred in other domestic animals and that we will not find a few specific genes that were critical for domestication," Andersson says.

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