Out of a rabbit hole: research reveals genetic basis for animal domestication

New research presents key findings in the DNA make-up of the common mammal’s brain and nervous system, which determines how wild rabbits were genetically transformed to domestic rabbits. 

The study predicts a similar diversity of gene variants that occur in humans and triggers our personality traits.

The study, done in collaboration with scientists from The Geonome Analysis Centre (TGAC UK), The Broad Institute (US) and Uppsala University (Sweden), in addition to other international scientists in the rabbit research community, have made a breakthrough in their field by comparing wild and domestic rabbits. The research paper reports that many gene developments were involved in the domestication of rabbits, particularly controlling the improvement of the brain and the nervous system.

The domestication of animals and plants, a prerequisite for the development of agriculture, is one of the most import technological revolutions during history of mankind. However, there has been little knowledge of what genetic changes were required to transform a wild animal into a domesticated form. No previous study on animal domestication has involved such a careful examination of genetic variation in the wild ancestral species, allowing the researchers to pinpoint the genetic changes that have occurred during rabbit domestication.

Federica Di Palma, co-first author and Director of Science at TGAC, said: “The rabbit is a model for very recent domestication, and interestingly, we found that changes in many of the domestic rabbit’s genes play a role and were also present in the wild ancestor. We also found that these variations occur in the non-coding DNA part of the genome, emphasising the regulatory nature of the genetic basis underlying domestication in rabbits.”

The scientists were baffled by the clearly heightened changes involved in the development of the brain and the nervous system among the genes particularly targeted during domestication, alluding to the drastic changes in behaviour between wild and domestic rabbits. “The results we have are very clear, the difference between a wild and a tame rabbit is not which genes they carry, but how the expression of their genes is regulated,” said Leif Andersson, co-author and Head of Medical Biochemistry and Microbiology at Uppsala University.

Wild rabbits have very strong reactions due to them being hunted by other species and humans, and therefore, must be very alert to survive in the wild. Darwin used domestic animals as a proof-of-principle that it is possible to change the phenotype by selection. The current study has now been able to reveal the genetic basis for the remarkable change in behaviour, giving important new insights about the domestication process.

“Our study shows that the wild rabbit is a highly polymorphic species that carries rare gene variants that were favourable during domestication, and the accumulation of many small changes led to the evolution of the domestic rabbit in which the strong flight response had been inhibited. We predict that a similar process has occurred in other domestic animals and there will not be specific genes that are critical for domestication. It is very likely that a similar diversity of gene variants affecting the brain and the nervous system occurs in the human population and underlies differences in personality and behaviour, for instance, response to fear,” said Leif.

The scientists first sequenced the entire genome of one domestic rabbit to develop a reference genome assembly. They then re-sequenced the entire genome of domestic rabbits, representing six different breeds, and the wild rabbits genomes were sampled at 14 different places across the Iberian Peninsula and southern France. The rabbit is an outstanding model for genetic studies of domestication. The domestication of rabbits is relatively recent; and the region is still densely populated with wild rabbits.

Rabbit domestication has primarily occurred by altering the frequencies of gene variants that were already present in the wild ancestor. The new research shows that domestication has primarily involved many minor gene changes and few drastic gene changes. There were very few examples where a gene variant common in domestic rabbits had completely replaced the gene variant present in wild rabbits; it was rather the shifts in frequencies of those variants that were favoured in domestic rabbits. 

“An interesting consequence of this is that if you release domestic rabbits into the wild, there is an opportunity for back selection of those genes that have been altered during domestication because the ‘wild-type’ variant has rarely been completely lost. In fact, this is what we plan to study next,” said Leif.

Domestication of animals started as early as 9,000 to 15,000 years ago and initially involved dogs, cattle, sheep, goats and pigs. The rabbit was domesticated much later, about 1,400 years ago, at monasteries in southern France. It has been claimed that rabbits were domesticated because the Catholic Church had declared that young rabbit was not considered meat but fish and could, therefore, be eaten during lent. When domestication occurred, the wild ancestor, the European rabbit (Oryctolagus cuniculus), was only recorded on the Iberian Peninsula and in southern France.

The paper, titled: “Rabbit genome analysis reveals a polygenic basis for phenotypic change during domestication” is published in Science.

TGAC is strategically funded by BBSRC and operates a National Capability to promote the application of genomics and bioinformatics to advance bioscience research and innovation.

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