Genes controlling the development of the brain and nervous system were fundamentally important for animal domestication, according to new research.
An international team of scientists have now made a breakthrough in understanding the genetic changes that tamed wild animals, which have long been a mystery.
The domestication of animals and plants, a prerequisite for the development of agriculture, is one of the most important technological revolutions in mankind's history.
Although the domestication of dogs and cattle started 9,000 to 15,000 years ago, the rabbit was domesticated much later, around 1,400 years ago at monasteries in southern France.
Miguel Carneiro, an author of the study from the Inbio-University of Porto, said rabbits were a good model for genetic studies of domestication as it happened fairly recently and we know where the domestication began.
For the study, scientists first sequenced the entire genome of one domestic rabbit to develop a reference genome assembly. Then they resequenced entire genomes of domestic rabbits representing six different breeds and wild rabbits sampled at 14 different places across the Iberian Peninsula and southern France.
Charles Darwin used domestic animals as a proof-of-principle that it was possible to change phenotypes by selection, writing in the Origin of Species: "No animal is more difficult to tame than the young of the wild rabbit; scarcely any animal is tamer than the young of the tame rabbit."
Now, scientists have been able to reveal the genetic basis for this remarkable change in behaviour.
Rabbit domestication has primarily occurred by altering the frequencies of gene variants that were already present in the wild ancestor.
"Our data shows that domestication primarily involved small changes in many genes and not drastic changes in a few genes," said senior co-author Kerstin Lindblad-Toh, of the Broad Institute of MIT and Harvard.
The team observed very few examples where a gene variant common in domestic rabbits had completely replaced the gene variant present in wild rabbits. It was rather shifts in frequencies of those variants that were favoured in domestic rabbits.
"A consequence of this is that if you release domestic rabbits into the wild, there is an opportunity for back selection at those genes that have been altered during domestication because the 'wild-type' variant has rarely been completely lost," said Carneiro.
The scientists found no example where a gene has been inactivated during rabbit domestication and there were many more changes in the non-coding part of the genome than in the parts of the genome that codes for protein.
The team concluded that the difference between a wild and a tame rabbit was not which genes they carried but how their genes are regulated - when and how much of each gene was used in different cells.
It revealed genes involved in the development of the brain and the nervous system had been altered during domestication.
The study was published in Science.