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Taming of Wild Rabbit Linked to Pattern Shifts in Neurologic Gene Regulation Variants

NEW YORK (GenomeWeb) — While the genetics behind animal domestication are complex and mostly uncharted, researchers have uncovered new evidence that appears to explain some of the genomic transformation of wild rabbits into a variety of tame bunnies.

The study, published this week in Science by a large international group of institutions, identified a number of SNPs in regions associated with brain and nervous system development genes whose frequency distinguished wild from domestic rabbits. The results imply that genetic changes affecting these processes may have been a hallmark of rabbit domestication, which would be consistent with the behavioral changes necessary for rabbits and other animals to adapt to life with humans.

Rabbits, it turns out — unlike other mammals whose domestication took place so long ago that their wild ancestors are sparsely spread or extinct — are remarkably suited to genetic comparison because their taming was taken up relatively recently — as little as 1,400 years ago — by monks in the south of France.

At the time of first domestication, the wild rabbit population was confined to France and the Iberian Peninsula in only a handful of subspecies. Meanwhile, wild rabbits closely related to these ancestors of the first domesticated monastery bunnies still roam the area, according to the study authors.

In their study, the rabbit researchers started from the ground up, creating a reference genome using Sanger sequencing of a single rabbit genome. They then used this to compare resequenced genomes of six domestic rabbit breeds and wild rabbits from 14 local populations across the Iberian Peninsula and southern France to try to pick out areas that appeared to distinguish one from the other.

According to the team's genomic comparison, rabbit domestication looks to have been driven by changes in the allele frequency of regulatory rather than coding gene variants.

Unlike breed-specific traits present in subsets of other domestic animals that are linked to simple, fixed changes in the genome, the genetic selection that morphed wild rabbits into tame rabbits appears to have been polygenic and complex, according to the study.

The researchers did not find variants that appeared statically in domestic versus wild rabbits, or vice versa. Instead, the frequency of many different variants differed between the tame and wild populations.

"Our data shows that domestication primarily involved small changes in many genes and not drastic changes in a few genes," Kerstin Lindblad-Toh, co-senior author of the study and director of vertebrate genome biology at the Broad Institute of MIT and Harvard, said in a statement highlighting the results.

The team also didn't identify inactivating nonsense or frame-shift mutations distinguishing tame from wild rabbits, which the authors wrote was consistent with studies of other mammals and suggests that gene loss is not a major player in animal domestication.

Further biological and functional analyses revealed that the variants whose allele frequency differed in tame versus wild rabbits were highly enriched for genes implicated in the development of the brain and nervous system, which, the authors wrote, makes sense considering the phenotypic changes that take place in domestication, altering the behavior of animals in relation to humans.

In essence, the results paint a picture of many small changes in the regulation of genes associated with behavior and cognition combining in different ways in different individual animals to create overall population tameness.

According to the researchers, the data suggest that "no single genetic change is either necessary or sufficient for domestication," and that "because of the complex genetic background for tame behavior … domestic animals [appear to have] evolved by means of many mutations of small effect rather than by critical changes at only a few domestication loci."

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