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What’s Up, Doc? A Bevy of Brain and Behavior Genes Breed Bugs Bunny


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Back in the 600s, monks in southern France grew tired of eating fish during Lent. So they petitioned the Pope, informing him that rabbits—one of the country’s most delectable meats—were actually fish. The Pope agreed, and thus began the human domestication of rabbits.

Now, researchers at the Broad Institute in Cambridge, Massachusetts, with collaborators in Sweden, Portugal, and elsewhere, have compared the domesticated rabbit genome to the wild one and found that domesticated rabbits differ from wild rabbits at many genetic loci having to do with brain and behavior, rather than just a few “domestication genes.”

“The rabbit is really exciting because it’s the most recent domestication event,” said Kerstin Lindblad-Toh of the Broad Institute, co-lead investigator on the paper with Leif Andersson at Uppsala University, Sweden. “Also, the wild populations in southern France from which the rabbits were domesticated still exist...thus, the domestication is recent, well-established, and we can compare the current domesticated rabbits with their wild ancestors.”

For the past 10 years, Nuno Ferrand and his team at the Universidade do Porto in Vairao, Portugal have collected samples from several populations of wild rabbits in southern France. Working with the Broad Institute, the group performed a whole-genome resequencing of three pools of these wild rabbits, as well as sequencing of pooled samples from six breeds of domesticated rabbits. They also sequenced 11 pools of wild rabbits from the Iberian Peninsula and a close relative, the snowshoe hare.

The team found that the domesticated rabbit is most closely related to the southern France wild rabbits. More importantly, genes affecting behavior, brain development, and brain function were most changed. “And it wasn’t just a few genes, but thousands of loci that have allele frequency differences. It’s really quite exciting that there are so many loci involved and they all have to do with brain development,” said Lindblad-Toh.

Notably, changes in regulatory genes are prominent. “This makes sense because...if you change the tissues where the neurons are expressed a little bit, or the amount that’s expressed a little bit, you can fine tune the function of the brain and fine tune the behavior,” said Lindblad-Toh, which is just what’s needed when adapting to a slightly different environment, like living with humans.

Since no one knows exactly where or when dogs and other pets were domesticated, the genetic data from the recently tamed rabbit are precious.

“It’s important to learn about the mechanisms of genome evolution and about the function of the different parts of the human and mammalian genomes. How did we end up being the human beings that we are? Why have dogs or rabbits changed to be what they are?” said Lindblad-Toh. “This can teach us about human evolution, but also about what variants are involved in human complex disease.”


1. Carneiro M, Rubin CJ, Di Palma F, Albert FW, Alföldi J, Barrio AM, Pielberg G, Rafati N, Sayyab S, Turner-Maier J, Younis S, Afonso S, Aken B, Alves JM, Barrell D, Bolet G, Boucher S, Burbano HA, Campos R, Chang JL, Duranthon V, Fontanesi L, Garreau H, Heiman D, Johnson J, Mage RG, Peng Z, Queney G, Rogel-Gaillard C, Ruffier M, Searle S, Villafuerte R, Xiong A, Young S, Forsberg-Nilsson K, Good JM, Lander ES, Ferrand N, Lindblad-Toh K, Andersson L. Rabbit genome analysis reveals a polygenic basis for phenotypic change during domestication. Science. 2014 Aug 29;345(6200):1074-9.

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