Abstract
During the second part of the twentieth century, Belyaev selected tame and aggressive foxes (Vulpes vulpes), in an effort known as the “farm-fox experiment”, to recapitulate the process of animal domestication. Using these tame and aggressive foxes as founders of segregant backcross and intercross populations we have employed interval mapping to identify a locus for tame behavior on fox chromosome VVU12. This locus is orthologous to, and therefore validates, a genomic region recently implicated in canine domestication. The tame versus aggressive behavioral phenotype was characterized as the first principal component (PC) of a PC matrix made up of many distinct behavioral traits (e.g. wags tail; comes to the front of the cage; allows head to be touched; holds observer’s hand with its mouth; etc.). Mean values of this PC for F1, backcross and intercross populations defined a linear gradient of heritable behavior ranging from tame to aggressive. The second PC did not follow such a gradient, but also mapped to VVU12, and distinguished between active and passive behaviors. These data suggest that (1) there are at least two VVU12 loci associated with behavior; (2) expression of these loci is dependent on interactions with other parts of the genome (the genome context) and therefore varies from one crossbred population to another depending on the individual parents that participated in the cross.
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Acknowledgements
We are grateful to Irina V. Pivovarova, Tatyana I. Semenova, Vasiliy V. Ivaykin, Vera I. Vladimirova, Tatyana V. Konovalova, Vera L. Haustova, and all the animal keepers at the ICG experimental farm for research assistance. We want to thank Franz Goller for insightful discussions during the writing of the manuscript. We express our profound gratitude to Marshfield Laboratories Mammalian Genotyping Service for genotyping support. Research was supported by NIH grants MH077811, EY06855, GM63056, NIH FIRCA grants TW007056 and TW008098, grants # 05-04-4837 and # 06-04-48142 of the Russian Fund for Basic Research, Program of the Russian Academy of Sciences: “Biodiversity and Genome Dynamics”, and Cornell VERGE Initiative.
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Supplementary Table I
A list of 98 traits used for principal component analysis and frequencies of trait observations in each fox population. Frequencies of traits in the F2 population were calculated using both F2_1 and F2_2 data sets (PDF 37 kb)
Supplementary Table II
The percentage of variation in silver fox behavior explained by the first two principal components, calculated for individual test steps and all test steps combined. Principal component one explains percentage of total variation; principal component two explains a percentage of residual variation (XLS 19 kb)
Supplementary Table III
A list of markers used for genotyping fox pedigrees. BCT_1 and BCA pedigrees were genotyped at Marshfield Laboratories and Cornell University. The sources of genotypes for these pedigrees are indicated in corresponding columns. All BCT_2 and F2 pedigrees were genotyped at Cornell University. About 50% of markers used for genotyping F2 pedigrees were genotyped in multiplexed PCRs. The information about markers used in multiplexed PCRs (multiplex name, dye, product size, and Tm) is listed in correspondent columns (PDF 58 kb)
Supplementary Table IV
A list of fox microsatellite markers developed in this study and used for genotyping fox pedigrees (PDF 25 kb)
Supplementary Fig. 1
Population distributions for the first two principal components of silver fox behavior for individual test steps. The first letter in the principal component abbreviation indicates the individual test step for which this principal component was calculated (e.g., A.PC1 corresponds to the PC1 defined using behavioral observations from the test step A (“Observer stays calmly near the closed cage”). Aggr = selectively bred “aggressive” founder population; BCA = backcross-to-aggressive; F2_1 and F2_2 = Two F2 populations (F1 x F1); F1 = F1 population (“tame” x “aggressive”); BCT_1 and BCT_2 = Two backcross-to-tame populations; Tame = selectively bred “tame” founder population. Horizontal bars within each box indicate the population median. Confidence intervals for the medians are shown as notches such that two distributions with non overlapping notches are significantly different (p = 0.05). 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. (TIFF 21105 kb)
Supplementary Fig. 2
Fox LOD 2.0 meiotic linkage map of the silver fox (Vulpes vulpes). Markers on the left map to unique positions with confidence 100:1 (LOD 2.0). Markers on the right are drawn in their most likely position, determined at the latter confidence threshold. The color is used to simplify identification of markers that were not mapped to the unique positions. The LOD 2.0 map was used for the genome wide association studies. (PDF 957 kb)
Supplementary Fig. 3
Comprehensive map of the fox genome. Markers not mappable to unique positions at the LOD 2.0 threshold were placed without statistical support (LOD 0.0) to generate this comprehensive map for use in interval mapping. (PDF 308 kb)
Supplementary Fig. 4
Interval mapping of behavioral components 1 and 2 for individual test steps and all test steps combined in different segregating populations. Interval mapping results are presented only for the first two principal components for which QTLs on VVU12 exceeded the chromosome wide significance threshold at p < 0.01 or experiment wide threshold at p < 0.05. The significance of each QTL is presented in Table 3. Interval mapping using GridQTL software was undertaken for the two data sets: a) backcross-to-tame population (BCT_1 and BCT_2), b) F2 population (F2_1 and F2_2) separately. a.i. Interval mapping of PC1 (all test steps) in the backcross-to-tame population; a.ii. Interval mapping of PC2 (all test steps) in the backcross-to-tame population; a.iii. Interval mapping of A.PC1, defined using behavioral observations for test step A, in the backcross-to-tame population; a.iv. Interval mapping of B.PC1, defined using behavioral observations for test step B, in the backcross-to-tame population; a.v. Interval mapping of C.PC2, defined using behavioral observations for test step C, in the backcross-to-tame population; b.i. Interval mapping of PC2 (all test steps) in the F2 population; b.ii. Interval mapping of C.PC1, defined using behavioral observations for test step C, in the F2 population. The F statistics (y-axis) is graphed as a function of cM distance across the VVU12 chromosome. Interval mapping in individual populations yields supports for behavioral loci on VVU12, located broadly between 10 and 60 cM. (TIFF 16743 kb)
Supplementary Fig. 5
Meiotic linkage map of fox chromosome 12 (VVU12), aligned and compared to the dog genome. The linkage map of the VVU12 was constructed with the LOD 2.0 support. Positions of the corresponding markers in the dog genome were identified using BLAT (USCS Genome Browser, Santa-Cruz, CA). (TIFF 15470 kb)
Supplementary Fig. 6
Interval mapping of traits with highly significant or not significant loadings for C.PC2. For each trait, the signed F statistic (y-axis) from GridQTL is plotted as a function of cM distance across VVU12 (x-axis). The sign of the F statistic indicates the direction and parent-of-origin of the additive allele effect (i.e. positivity indicates that the allele originating from the tame population increases the frequency of the observed trait in the segregating population, and negativity indicates that the “tame” allele decreases the trait frequency). a. Trait C7, “Observer can first touch fox in zones 5-6” has highest negative loading for C.PC2; b. Trait C39, “Moved forward at least one zone during the step” has highest positive loading for C.PC2; c. Trait C8, “Lies down during a contact for at least 5 s” is not significant for C.PC2 but this trait is highly significant for C.PC1. Significance of trait loadings is presented in Table 5. Traits were mapped in four segregating populations: BCT_1 = dotted line, BCT_2 = dot dash line, F2 = dashed line, BCA = continuous line. Trait C7 (passive trait) maps to 60-100 cM region on VVU12 in both backcross-to-tame populations with the “tame” allele having opposite effect in BCT_1 and BCT_2. Trait C39 (active trait) maps broadly to the 0-60 cM region in the BCT_2 and BCA populations and to the 10-80 cM region in the BCT_1 population. The tame allele decreases the frequency of the trait in both BCT populations and increases the frequency of the trait in the BCA population. Trait C8 maps to the 10-60 cM region on VVU12 in the F2 population but not in the backcross-to-tame populations. (TIFF 10527 kb)
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Kukekova, A.V., Trut, L.N., Chase, K. et al. Mapping Loci for Fox Domestication: Deconstruction/Reconstruction of a Behavioral Phenotype. Behav Genet 41, 593–606 (2011). https://doi.org/10.1007/s10519-010-9418-1
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DOI: https://doi.org/10.1007/s10519-010-9418-1