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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 F2 population including 537 individuals by cross-breeding tame and aggressive fox strains. 98 fox behavioral traits were recorded during social interaction with a human experimenter in a standard four-step test. Patterns of fox behaviors during the test were evaluated using principal component (PC) analysis. Genetic mapping identified eight unique significant and suggestive QTL. Mapping results for the PC phenotypes from different test steps showed little overlap suggesting that different QTL are involved in regulation of behaviors exhibited in different behavioral contexts. Many individual behavioral traits mapped to the same genomic regions as PC phenotypes. This provides additional information about specific behaviors regulated by these loci. Further, three pairs of epistatic loci were also identified for PC phenotypes suggesting more complex genetic architecture of the behavioral differences between the two strains than what has previously been observed.

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We are grateful to Irina V. Pivovarova, Tatyana I. Semenova, and all the animal keepers at the ICG experimental farm for research assistance. We thank K. Gordon Lark and Kevin Chase for advice and important discussions. The project was supported by National Institutes of Health Grant MH077811, NIH FIRCA Grant TW008098, USDA Federal Hatch Project #538922, Program of the Siberian Branch of the Russian Academy of Sciences #0324-2015-0007, Grant #13-04-00420 from the Russian Fund for Basic Research, and Campus Research Board Grant from the University of Illinois at Urbana-Champaign.

Author information

Correspondence to Anna V. Kukekova.

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Conflict of interest

Ronald M. Nelson, Svetlana V. Temnykh, Jennifer L. Johnson, Anastasiya V. Kharlamova, Anastasiya V. Vladimirova, Rimma G. Gulevich, Darya V. Shepeleva, Irina N. Oskina, Gregory M. Acland, Lars Rönnegård, Lyudmila N. Trut, Örjan Carlborg, Anna V. Kukekova declare that they have no conflict of interest.

Human and animal rights and informed consent

All institutional and national guidelines for the care and use of laboratory animals were followed. All animal procedures at the Institute of Cytology and Genetics of the Russian Academy of Sciences complied with standards for humane care and use of laboratory animals by foreign institutions.

Additional information

Edited by Stephen Maxson.

Ronald M. Nelson, Svetlana V. Temnykh, and Jennifer L. Johnson have contributed equally to this work.

Irina N. Oskina—deceased.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary Table 1. The F2 pedigrees used for QTL mapping. Parents are listed only for F1 and F2 individuals.

Supplementary Table 2. Contribution of each of tame and aggressive grandparent to the F2 generation.

Supplementary Table 3. Microsatellite markers used for genotyping fox F2 pedigrees and their locations on the meiotic linkage map (LOD 0.0).

Supplementary Table 4. List of traits used for PC analysis and frequency of trait observations in aggressive, tame, F1, and F2 populations (A) and average PC values in parental and cross-bred populations (B). For aggressive, tame, and F1 populations frequency of the trait observations in the test #1 are listed, for the F2 population, mean of frequency observations in the tests #1 and #2 is presented. The standard test included four steps: Step A - observer stands calmly near the closed cage but does not deliberately try to attract the fox’s attention; Step B - observer opens the cage door, remains nearby but does not initiate any contact with the fox; Step C - observer attempts to touch the fox; Step D - observer closes the cage door, then stays calmly near the closed cage. The zones 1 and 2 are located in the front of the cage, zones 5 and 6 are located in the back of the cage, and zone 3 and 4 are in the middle. The zone 2 and 2a are the closest to a human experimenter. Tame = tame population; Aggr = aggressive population, BCT = backcross-to-tame, BCA = backcross-to-aggressive.

Supplementary Table 5. Trait loadings in the first three PCs calculated for each individual test step. The traits with highest absolute loadings to the corresponding PC are highlighted by green (top 20th percentile) and blue (lowest 20th percentile).

Supplementary Table 6. Estimated additive (a) and dominance (d) effects of QTL identified for PC1 traits and estimation of population differences and residual variance explained by each QTL. Tame = tame population; Aggr = aggressive population.

Supplementary Table 7. Correlation coefficients for pairs of PC1 phenotypes in parental and experimental populations. BCT = backcross-to-tame strain; BCA = backcross-to-aggressive strain.

Supplementary Figure 1. Box plots of first three PCs calculated for each individual test step. Horizontal bars within the boxes indicate the population median. The bottom and top edges of the boxes indicate the 25 and 75 percentiles. The whiskers indicate the range of data up to 1.5 times the interquartile range. Outliers are shown as individual circles. Data for four populations Tame = tame, Aggr = aggressive, F1 and F2 are shown.

Supplementary Figure 2. Histogram of the first three PCs calculated for each individual test step. Data for F2 population are shown.

Supplementary Figure 3. Heat map of 98 traits scored in the standard test. Spearman Rank correlation of 98 traits was calculated for all 1287 individuals included in PC analysis. The traits are ordered using two parameters: 1) test step; 2) correlation coefficient with step specific PC1 phenotype.

Supplementary Figures 4. Main effect QTL for PC phenotypes. QTL plot for each PC phenotype with significant (p = 0.05) and suggested (p ≈ 0.20) QTL thresholds indicated. Vertical dashed lines indicate boundaries of fox autosomes.

Supplementary Figure 5. QTL plot for each trait. QTL plot for each trait with genome-wide significance threshold (p=0.05) indicated (F-value = 8.3). See also Table 4.

Supplementary Figures 6. QTL plot for each PC and the associated traits. QTL plots for each of the PC phenotypes are in blue. Associated traits in the 20th percentile (see Table 2 for details) indicated in red (TL-20). Genome-wide significance threshold (p=0.05) is indicated (F-value of 8.3). See also Supplementary Figures 4 and 5 for individual PC and trait profiles.

Supplementary Figure 7. Correlation between B.PC1 and C.PC1 phenotypes in tame, aggressive, backcross-to-tame, backcross-to-aggressive, and F2 populations.

Supplementary Figure 8. Genotype-phenotype map for C.PC1 on VVU1. Genotype-phenotype map and associated QTL position on chromosome 1 (65 cM) for the phenotype C.PC1 and traits with significant contribution to C.PC1 (Table 2). The QTL plot indicates a position in the genome for which the association between phenotype and genotype is presented (vertical red line). The box-plot indicates the C.PC1 phenotype values for the three genotypic classes (TT, TA, and AA). The stacked bar graph for significant traits demonstrates a relative proportion of F2 individuals from the three genotypic classes (TT, TA and AA) which did not show the trait (0) demonstrated it in one of the two tests (0.5), or in both tests analyzed (1).

Supplementary Figure 9. Genotype-phenotype map for C.PC1 on VVU5. Genotype-phenotype map and associated QTL position on chromosome 1 (65 cM) for the phenotype C.PC1 and traits with significant contribution to C.PC1 (Table 2). The QTL plot indicates a position in the genome for which the association between phenotype and genotype is presented (vertical red line). The box-plot indicates the C.PC1 phenotype values for the three genotypic classes (TT, TA, and AA). The stacked bar graph for significant traits demonstrates a relative proportion of F2 individuals from the three genotypic classes (TT, TA and AA) which did not show the trait (0) demonstrated it in one of the two tests (0.5), or in both tests analyzed (1).

Supplementary Figure 10. Interacting pairs of loci for B.PC1 and C.PC1 phenotypes. Main effect QTL for B.PC1 and C.PC1 in the fox genome indicated on the X- and Y-axes with a genome-wide significance threshold of 5%. 2D plot of SSE (residual sum of squares) of all epistatic pairs (low values darker). Significant interacting pairs indicated by blue dots. See Table 5 for details.

Supplementary File 1. R code used in simulation study.

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Nelson, R.M., Temnykh, S.V., Johnson, J.L. et al. Genetics of Interactive Behavior in Silver Foxes (Vulpes vulpes). Behav Genet 47, 88–101 (2017). https://doi.org/10.1007/s10519-016-9815-1

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  • Behavior genetics
  • Social behavior
  • Quantitative trait loci
  • Domestication
  • Aggression
  • Epistasis
  • Vulpes vulpes
  • Canis familiaris