Behavior Genetics

, Volume 41, Issue 4, pp 593–606 | Cite as

Mapping Loci for Fox Domestication: Deconstruction/Reconstruction of a Behavioral Phenotype

  • Anna V. Kukekova
  • Lyudmila N. Trut
  • Kevin Chase
  • Anastasiya V. Kharlamova
  • Jennifer L. Johnson
  • Svetlana V. Temnykh
  • Irina N. Oskina
  • Rimma G. Gulevich
  • Anastasiya V. Vladimirova
  • Simon Klebanov
  • Darya V. Shepeleva
  • Svetlana G. Shikhevich
  • Gregory M. Acland
  • Karl G. Lark
ORIGINAL RESEARCH

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.

Keywords

Behavior genetics Domestication Social behavior Vulpes vulpes Canis familiaris 

Supplementary material

10519_2010_9418_MOESM1_ESM.pdf (38 kb)
Supplementary Table IA 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)
10519_2010_9418_MOESM2_ESM.xls (19 kb)
Supplementary Table IIThe 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)
10519_2010_9418_MOESM3_ESM.pdf (58 kb)
Supplementary Table IIIA 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)
10519_2010_9418_MOESM4_ESM.pdf (25 kb)
Supplementary Table IVA list of fox microsatellite markers developed in this study and used for genotyping fox pedigrees (PDF 25 kb)
10519_2010_9418_MOESM5_ESM.tif (20.6 mb)
Supplementary Fig. 1Population 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)
10519_2010_9418_MOESM6_ESM.pdf (957 kb)
Supplementary Fig. 2Fox 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)
10519_2010_9418_MOESM7_ESM.pdf (309 kb)
Supplementary Fig. 3Comprehensive 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)
10519_2010_9418_MOESM8_ESM.tif (16.4 mb)
Supplementary Fig. 4Interval 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)
10519_2010_9418_MOESM9_ESM.tif (15.1 mb)
Supplementary Fig. 5Meiotic 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)
10519_2010_9418_MOESM10_ESM.tif (10.3 mb)
Supplementary Fig. 6Interval 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)

References

  1. Albert FW, Carlborg O, Plyusnina I, Besnier F, Hedwig D, Lautenschläger S, Lorenz D, McIntosh J, Neumann C, Richter H, Zeising C, Kozhemyakina R, Shchepina O, Kratzsch J, Trut L, Teupser D, Thiery J, Schöneberg T, Andersson L, Pääbo S (2009) Genetic architecture of tameness in a rat model of animal domestication. Genetics 182(2):541–554PubMedCrossRefGoogle Scholar
  2. Gácsi M, Miklósi A, Varga O, Topál J, Csányi V (2004) Are readers of our face readers of our minds? Dogs (Canis familiaris) show situation-dependent recognition of human’s attention. Anim Cogn 7(3):144–153PubMedCrossRefGoogle Scholar
  3. Gácsi M, Gyori B, Miklósi A, Virányi Z, Kubinyi E, Topál J, Csányi V (2005) Species-specific differences and similarities in the behavior of hand-raised dog and wolf pups in social situations with humans. Dev Psychobiol 47(2):111–122PubMedCrossRefGoogle Scholar
  4. Gácsi M, Györi B, Virányi Z, Kubinyi E, Range F, Belényi B, Miklósi A (2009) Explaining dog wolf differences in utilizing human pointing gestures: selection for synergistic shifts in the development of some social skills. PLoS One 4(8):e6584PubMedCrossRefGoogle Scholar
  5. Gilbert JR, Vance JM (1994) Isolation of genomic DNA from mammalian cells. In: Current protocols in human genetics. Wiley, Appendix A.3B, pp 1–6Google Scholar
  6. Green P, Fall K, Crooks S (1990) Documentation for CRI-MAP, version 2.4. Washington University School of Medicine, St. LouisGoogle Scholar
  7. Hare B, Brown M, Williamson C, Tomasello M (2002) The domestication of social cognition in dogs. Science 298(5598):1634–1636PubMedCrossRefGoogle Scholar
  8. Hare B, Plyusnina I, Ignacio N, Schepina O, Stepika A, Wrangham R, Trut L (2005) Social cognitive evolution in captive foxes is a correlated by-product of experimental domestication. Curr Biol 15(3):226–230PubMedCrossRefGoogle Scholar
  9. Kukekova AV, Trut LN, Oskina IN, Kharlamova AV, Shikhevich SG, Kirkness EF, Aguirre GD, Acland GM (2004) A marker set for construction of a genetic map of the silver fox (Vulpes vulpes). J Hered 95:185–194PubMedCrossRefGoogle Scholar
  10. Kukekova AV, Oskina IN, Kharlamova AV, Chase K, Erb HN, Aguirre GD, Lark KG, Trut LN, Acland GM (2005) In: Ostrander EA, Giger U, Lindblad-Toh K (eds) The dog and its genome. Cold Spring Harbor Laboratory Press, Woodbury NY, pp 515–538Google Scholar
  11. Kukekova AV, Trut LN, Oskina IN, Johnson JL, Temnykh SV, Kharlamova AV, Shepeleva DV, Gulievich RG, Shikhevich SG, Graphodatsky AS, Aguirre GD, Acland GM (2007) A meiotic linkage map of the silver fox, aligned and compared to the canine genome. Genome Res 17(3):387–399PubMedCrossRefGoogle Scholar
  12. Kukekova AV, Trut LN, Chase K, Shepeleva DV, Vladimirova AV, Kharlamova AV, Oskina IN, Stepika A, Klebanov S, Erb HN, Acland GM (2008) Measurement of segregating behaviors in experimental silver fox pedigrees. Behav Genet 38(2):185–194PubMedCrossRefGoogle Scholar
  13. Manly B (1997) Randomization, bootstrap, and Monte Carlo methods in biology, 2nd edn. Chapman & Hall, LondonGoogle Scholar
  14. Matise TC, Perlin M, Chakravarti A (1994) Automated construction of genetic linkage maps using an expert system (MultiMap): a human genome linkage map. Nat Genet 6:384–390PubMedCrossRefGoogle Scholar
  15. Miklósi A (2009) Evolutionary approach to communication between humans and dogs. Vet Res Commun 33(Suppl 1):53–59PubMedCrossRefGoogle Scholar
  16. R Development Core Team (2006) R: A Language and Environment for Statistical Computing. R Foundation for Statistical Computing, ViennaGoogle Scholar
  17. Saetre P, Strandberg E, Sundgren PE, Pettersson U, Jazin E, Bergström TF (2006) The genetic contribution to canine personality. Genes Brain Behav 5(3):240–248PubMedCrossRefGoogle Scholar
  18. Seaton G, Haley CS, Knott SA, Kearsey M, Visscher PM (2002) QTL Express: mapping quantitative trait loci in simple and complex pedigrees. Bioinformatics 18(2):339–340PubMedCrossRefGoogle Scholar
  19. Seaton G, Hernandez J, Grunchec JA, White I, Allen J, De Koning DJ, Wei W, Berry D, Haley C, Knott S. (2006) GridQTL: a grid portal for QTL mapping of compute intensive datasets. In: Proceedings of the 8th world congress on genetics applied to livestock production, August 13–18. Belo Horizonte, BrazilGoogle Scholar
  20. Svartberg K (2002) Shyness–boldness predicts performance in working dogs. Appl Anim Behav Sci 79:157–174CrossRefGoogle Scholar
  21. Svartberg K (2005) A comparison of behaviour in test and in everyday life: evidence of three consistent boldness-related personality traits in dogs. Appl Anim Behav Sci 91:103–128CrossRefGoogle Scholar
  22. Svartberg K, Forkman B (2002) Personality traits in the domestic dog (Canis familiaris). Appl Anim Behav Sci 79:133–155CrossRefGoogle Scholar
  23. Topál J, Gácsi M, Miklósi Á, Virányi Zs, Kubinyi E, Csányi V (2005) The effect of domestication and socialization on attachment to human: a comparative study on hand reared wolves and differently socialized dog puppies. Anim Behav 70:1367–1375CrossRefGoogle Scholar
  24. Trut LN (1980) The genetics and phenogenetics of domestic behaviour, vol 2. In: Problems in general genetics. Proceeding of the XIV international congress of genetics. Mir Publishers, Moscow, pp 123–136Google Scholar
  25. Trut LN (1999) Early canid domestication: the farm fox experiment. Am Sci 87:160–169Google Scholar
  26. Trut LN (2001) Experimental studies of early canid domestication. In: Ruvinsky A, Sampson J (eds) The genetics of the dog. CABI, New York, pp 15–43CrossRefGoogle Scholar
  27. Trut LN, Pliusnina IZ, Oskina IN (2004) An experiment on fox domestication and debatable issues of evolution of the dog. Genetika (Russ.) 40:794–807Google Scholar
  28. Trut L, Oskina I, Kharlamova A (2009) Animal evolution during domestication: the domesticated fox as a model. Bioessays 31(3):349–360PubMedCrossRefGoogle Scholar
  29. Udell MA, Dorey NR, Wynne CDL (2008) Wolves outperform dogs in following human social cues. Anim Behav 76:1767–1773CrossRefGoogle Scholar
  30. Venables WN, Ripley BD (2002) Modern applied statistics with S, 4th edn. Springer, New YorkGoogle Scholar
  31. vonHoldt BM, Pollinger JP, Lohmueller KE, Han E, Parker HG, Quignon P, Degenhardt JD, Boyko AR, Earl DA, Auton A, Reynolds A, Bryc K, Brisbin A, Knowles JC, Mosher DS, Spady TC, Elkahloun A, Geffen E, Pilot M, Jedrzejewski W, Greco C, Randi E, Bannasch D, Wilton A, Shearman J, Musiani M, Cargill M, Jones PG, Qian Z, Huang W, Ding ZL, Zhang YP, Bustamante CD, Ostrander EA, Novembre J, Wayne RK (2010) Genome-wide SNP and haplotype analyses reveal a rich history underlying dog domestication. Nature 464(7290):898–902PubMedCrossRefGoogle Scholar
  32. Wilson DS, Clark AB, Coleman K, Dearstyne T (1994) Shyness and boldness in humans and other animals. Trends Ecol Evol 9:442–446CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Anna V. Kukekova
    • 1
  • Lyudmila N. Trut
    • 2
  • Kevin Chase
    • 3
  • Anastasiya V. Kharlamova
    • 2
  • Jennifer L. Johnson
    • 1
  • Svetlana V. Temnykh
    • 1
  • Irina N. Oskina
    • 2
  • Rimma G. Gulevich
    • 2
  • Anastasiya V. Vladimirova
    • 2
  • Simon Klebanov
    • 4
  • Darya V. Shepeleva
    • 2
  • Svetlana G. Shikhevich
    • 2
  • Gregory M. Acland
    • 1
  • Karl G. Lark
    • 3
  1. 1.James A. Baker Institute for Animal HealthCornell UniversityIthacaUSA
  2. 2.Institute of Cytology and Genetics of the Russian Academy of SciencesNovosibirskRussia
  3. 3.Department of BiologyUniversity of UtahSalt Lake CityUSA
  4. 4.New York Obesity Research Center, St. Luke’s-Roosevelt Hospital CenterNew YorkUSA

Personalised recommendations