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

Anna V Kukekova,Stephen J O’Brien,Yury Herbeck,Jennifer L Johnson,Xiaozhu Wang ,Polina L Perelman,Anastasiya V Kharlamova,Halie M Rando,Zijun Xiong,Lyudmila N Trut,Andrew G Clark,Klaus‐Peter Koepfli ,Jessica P Hekman,Anastasiya V Vladimirova,Natalia A Serdyukova ,Shaohong Feng,Violetta Beklemischeva,Gregory M Acland,Р Г Гулевич ,Alexander S Graphodatsky ,Shi Ping Liu ,Xueyan Xiang,Guojie Zhang

doi:10.1038/s41559-018-0611-6

Abstract

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. 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. Other regions identified as likely to have been under selection in foxes include genes implicated in human neurological disorders, mouse behaviour and dog domestication. 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.

Highlights

There is no evidence that the fox was domesticated historically, 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 coburials of humans and dogs are found[10]
Alignment of the largest 500 scaffolds against the dog genome revealed that 84% of the scaffolds mapped to one dog chromosome, 15% mapped to two or more dog chromosomes and 1% could not be assigned to a position in the dog genome (Supplementary Table 3; Supplementary Fig. 2)
The 96% of the reads were aligned to the fox scaffolds and the 8,458,133 identified SNPs were retained for subsequent analyses (Supplementary Table 5)

Summary

Introduction

There is no evidence that the fox was domesticated historically, 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 coburials of humans and dogs are found[10]. 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]. 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. Beginning in the late 1960s, a complementary strain of foxes selected for aggressive behavior toward humans was developed and has proceeded for more than 40 generations[22,23]. A conventional population comparable to the farm-bred founder population of both selected strains has been maintained but was not subjected to deliberate selection for behaviour. We present the sequence assembly of the red fox genome and a population genetic analysis of whole re-sequenced genomes of foxes from the tame, aggressive and conventional farm-bred populations. Selection on the tame and aggressive strains is likely to have influenced genetic diversity and the fixation of variants across the genome, yielding a robust model for understanding the genetic basis of variation in social behaviour, which is a long-standing problem in evolutionary biology

Methods

Results

Conclusion