In 1959, the experimental domestication of farm-bred foxes began at the Institute of Cytology and Genetics of the Russian Academy of Sciences 18, 19, 20, 21, 22, 23. Conventional farm-bred foxes have adapted to the farm environment, yet their behaviour still clearly differentiates them from dogs because they generally exhibit fear or aggression toward humans. Though many animal species are not well-suited to breeding in captivity 12, fox breeding has continued successfully for more than a century 11, 13, 14, 15, 16, 17. The first strong evidence of fox domestication comes instead from the late nineteenth century, when the farm breeding of red foxes for fur began in Prince Edward Island, Canada 11. There is no evidence that the fox was domesticated historically, although a red fox was found co-buried with humans in a Natufian grave from 14.5–11.6 thousand years ago at a southern Levant site in northern Jordan 9, the same geographic region where the oldest co-burials of humans and dogs are found 10. The dog, on the other hand, has become widespread for a different reason: it was domesticated from the grey wolf at least 15,000 years ago 7, 8 and became ‘man’s best friend’. The red fox has a geographic range wider than that of any other wild species in the order Carnivora 2 and has even become a common resident of many major cities 3, 4, 5, 6. However, these two species occupy very different ecological niches. The red fox ( Vulpes vulpes) and the domestic dog ( Canis familiaris) are closely related species that only diverged about 10 million years ago within the family Canidae 1. The fox represents a powerful model for the genetic analysis of affiliative and aggressive behaviours that can benefit genetic studies of behaviour in dogs and other mammals, including humans. Other regions identified as likely to have been under selection in foxes include genes implicated in human neurological disorders, mouse behaviour and dog domestication. A strong positional candidate gene for tame behaviour was highlighted: SorCS1, which encodes the main trafficking protein for AMPA glutamate receptors and neurexins and suggests a role for synaptic plasticity in fox domestication. Analysis of the re-sequenced genomes identified 103 regions with either significantly decreased heterozygosity in one of the three populations or increased divergence between the populations. Here we sequenced and assembled the red fox genome and re-sequenced a subset of foxes from the tame, aggressive and conventional farm-bred populations to identify genomic regions associated with the response to selection for behaviour. Strains of red fox ( Vulpes vulpes) with markedly different behavioural phenotypes have been developed in the famous long-term selective breeding programme known as the Russian farm-fox experiment.
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