Missing history of a modern domesticate: Historical demographics and genetic diversity in farm-bred red fox populations.

The first record of captive-bred red foxes (Vulpes vulpes) dates to 1896 when a breeding enterprise emerged in the provinces of Atlantic Canada. Because its domestication happened during recent history, the red fox offers a unique opportunity to examine the genetic diversity of an emerging domesticated species in the context of documented historical and economic influences. In particular, the historical record suggests that North American and Eurasian farm-bred populations likely experienced different demographic trajectories.

The brain of the silver fox (Vulpes vulpes): a neuroanatomical reference of cell-stained histological and MRI images.

Although the silver fox (Vulpes vulpes) has been largely overlooked by neuroscientists, it has the potential to serve as a powerful model for the investigation of brain-behavior relationships. The silver fox is a melanistic variant of the red fox. Within this species, the long-running Russian farm-fox experiment has resulted in different strains bred to show divergent behavior.

Defining hippocampal area CA2 in the fox (Vulpes vulpes) brain.

Since 1959, the Russian Farm-Fox study has bred foxes to be either tame or, more recently, aggressive, and scientists have used them to gain insight into the brain structures associated with these behavioral features. In mice, hippocampal area CA2 has emerged as one of the essential regulators of social aggression, and so to eventually determine whether we could identify differences in CA2 between tame and aggressive foxes, we first sought to identify CA2 in foxes (Vulpes vulpes). As no clearly defined area of CA2 has been described in species such as cats, dogs, or pigs, it was not at all clear whether CA2 could be identified in foxes.

Neuromorphological Changes following Selection for Tameness and Aggression in the Russian Farm-Fox experiment.

The Russian farm-fox experiment is an unusually long-running and well-controlled study designed to replicate wolf-to-dog domestication. As such, it offers an unprecedented window onto the neural mechanisms governing the evolution of behavior. Here we report evolved changes to gray matter morphology resulting from selection for tameness versus aggressive responses toward humans in a sample of 30 male fox brains.

Hypothalamic transcriptome of tame and aggressive silver foxes (Vulpes vulpes) identifies gene expression differences shared across brain regions.

The underlying neurological events accompanying dog domestication remain elusive. To reconstruct the domestication process in an experimental setting, silver foxes (Vulpes vulpes) have been deliberately bred for tame vs aggressive behaviors for more than 50 generations at the Institute for Cytology and Genetics in Novosibirsk, Russia. The hypothalamus is an essential part of the hypothalamic-pituitary-adrenal axis and regulates the fight-or-flight response, and thus, we hypothesized that selective breeding for tameness/aggressiveness has shaped the hypothalamic transcriptomic profile.

The Red Fox Y-Chromosome in Comparative Context.

While the number of mammalian genome assemblies has proliferated, Y-chromosome assemblies have lagged behind. This discrepancy is caused by biological features of the Y-chromosome, such as its high repeat content, that present challenges to assembly with short-read, next-generation sequencing technologies. Partial Y-chromosome assemblies have been developed for the cat (), dog (), and grey wolf (), providing the opportunity to examine the red fox () Y-chromosome in the context of closely related species.

Genomic responses to selection for tame/aggressive behaviors in the silver fox ().

Animal domestication efforts have led to a shared spectrum of striking behavioral and morphological changes. To recapitulate this process, silver foxes have been selectively bred for tame and aggressive behaviors for more than 50 generations at the Institute for Cytology and Genetics in Novosibirsk, Russia. To understand the genetic basis and molecular mechanisms underlying the phenotypic changes, we profiled gene expression levels and coding SNP allele frequencies in two brain tissue specimens from 12 aggressive foxes and 12 tame foxes.

Author Correction: Red fox genome assembly identifies genomic regions associated with tame and aggressive behaviours.

In the version of this Article originally published, there were some errors in the affiliations: Stephen J. O'Brien's affiliations were incorrectly listed as 8,9; they should have been 7,9. Affiliation 3 was incorrectly named the Institute of Cytology and Genetics of the Russian Academy of Sciences; it should have read Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences.

Red fox genome assembly identifies genomic regions associated with tame and aggressive behaviours.

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. 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. 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.

Construction of Red Fox Chromosomal Fragments from the Short-Read Genome Assembly.

The genome of a red fox () was recently sequenced and assembled using next-generation sequencing (NGS). The assembly is of high quality, with 94X coverage and a scaffold N50 of 11.8 Mbp, but is split into 676,878 scaffolds, some of which are likely to contain assembly errors.

Anterior Pituitary Transcriptome Suggests Differences in ACTH Release in Tame and Aggressive Foxes.

Domesticated species exhibit a suite of behavioral, endocrinological, and morphological changes referred to as "domestication syndrome." These changes may include a reduction in reactivity of the hypothalamic-pituitary-adrenal (HPA) axis and specifically reduced adrenocorticotropic hormone release from the anterior pituitary. To investigate the biological mechanisms targeted during domestication, we investigated gene expression in the pituitaries of experimentally domesticated foxes ().

Y-Chromosome Markers for the Red Fox.

The de novo assembly of the red fox (Vulpes vulpes) genome has facilitated the development of genomic tools for the species. Efforts to identify the population history of red foxes in North America have previously been limited by a lack of information about the red fox Y-chromosome sequence. However, a megabase of red fox Y-chromosome sequence was recently identified over 2 scaffolds in the reference genome.

Facial shape differences between rats selected for tame and aggressive behaviors.

Domestication has been consistently accompanied by a suite of traits called the domestication syndrome. These include increased docility, changes in coat coloration, prolonged juvenile behaviors, modified function of adrenal glands and reduced craniofacial dimensions. Wilkins et al recently proposed that the mechanistic factor underlying traits that encompass the domestication syndrome was altered neural crest cell (NCC) development.

Genetics of Interactive Behavior in Silver Foxes (Vulpes vulpes).

Individuals involved in a social interaction exhibit different behavioral traits that, in combination, form the individual's behavioral responses. Selectively bred strains of silver foxes (Vulpes vulpes) demonstrate markedly different behaviors in their response to humans. To identify the genetic basis of these behavioral differences we constructed a large F population including 537 individuals by cross-breeding tame and aggressive fox strains.

Genotyping-By-Sequencing (GBS) Detects Genetic Structure and Confirms Behavioral QTL in Tame and Aggressive Foxes (Vulpes vulpes).

The silver fox (Vulpes vulpes) offers a novel model for studying the genetics of social behavior and animal domestication. Selection of foxes, separately, for tame and for aggressive behavior has yielded two strains with markedly different, genetically determined, behavioral phenotypes. Tame strain foxes are eager to establish human contact while foxes from the aggressive strain are aggressive and difficult to handle.

Selection for tameness, a key behavioral trait of domestication, increases adult hippocampal neurogenesis in foxes.

Work on laboratory and wild rodents suggests that domestication may impact on the extent of adult hippocampal neurogenesis and its responsiveness to regulatory factors. There is, however, no model of laboratory rodents and their nondomesticated conspecifics that would allow a controlled comparison of the effect of domestication. Here, we present a controlled within-species comparison of adult hippocampal neurogenesis in farm-bred foxes (Vulpes vulpes) that differ in their genetically determined degree of tameness.

Genetic influences on brain gene expression in rats selected for tameness and aggression.

Interindividual differences in many behaviors are partly due to genetic differences, but the identification of the genes and variants that influence behavior remains challenging. Here, we studied an F2 intercross of two outbred lines of rats selected for tame and aggressive behavior toward humans for >64 generations. By using a mapping approach that is able to identify genetic loci segregating within the lines, we identified four times more loci influencing tameness and aggression than by an approach that assumes fixation of causative alleles, suggesting that many causative loci were not driven to fixation by the selection.

A comparison of brain gene expression levels in domesticated and wild animals.

Domestication has led to similar changes in morphology and behavior in several animal species, raising the question whether similarities between different domestication events also exist at the molecular level. We used mRNA sequencing to analyze genome-wide gene expression patterns in brain frontal cortex in three pairs of domesticated and wild species (dogs and wolves, pigs and wild boars, and domesticated and wild rabbits). We compared the expression differences with those between domesticated guinea pigs and a distant wild relative (Cavia aperea) as well as between two lines of rats selected for tameness or aggression towards humans.

Genetics of behavior in the silver fox.

The silver fox provides a rich resource for investigating the genetics of behavior, with strains developed by intensely selective breeding that display markedly different behavioral phenotypes. Until recently, however, the tools for conducting molecular genetic investigations in this species were very limited. In this review, the history of development of this resource and the tools to exploit it are described.

Sequence comparison of prefrontal cortical brain transcriptome from a tame and an aggressive silver fox (Vulpes vulpes).

Background: Two strains of the silver fox (Vulpes vulpes), with markedly different behavioral phenotypes, have been developed by long-term selection for behavior. Foxes from the tame strain exhibit friendly behavior towards humans, paralleling the sociability of canine puppies, whereas foxes from the aggressive strain are defensive and exhibit aggression to humans. To understand the genetic differences underlying these behavioral phenotypes fox-specific genomic resources are needed.