Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Genomic consequences of intensive inbreeding in an isolated wolf population

Abstract

Inbreeding (mating between relatives) is a major concern for conservation as it decreases individual fitness and can increase the risk of population extinction. We used whole-genome resequencing of 97 grey wolves (Canis lupus) from the highly inbred Scandinavian wolf population to identify ‘identical-by-descent’ (IBD) chromosome segments as runs of homozygosity (ROH). This gave the high resolution required to precisely measure realized inbreeding as the IBD fraction of the genome in ROH (F ROH). We found a striking pattern of complete or near-complete homozygosity of entire chromosomes in many individuals. The majority of individual inbreeding was due to long IBD segments (>5 cM) originating from ancestors ≤10 generations ago, with 10 genomic regions showing very few ROH and forming candidate regions for containing loci contributing strongly to inbreeding depression. Inbreeding estimated with an extensive pedigree (F P) was strongly correlated with realized inbreeding measured with the entire genome (r 2 = 0.86). However, inbreeding measured with the whole genome was more strongly correlated with multi-locus heterozygosity estimated with as few as 500 single nucleotide polymorphisms, and with F ROH estimated with as few as 10,000 single nucleotide polymorphisms, than with F P. These results document in fine detail the genomic consequences of intensive inbreeding in a population of conservation concern.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Length distribution of ROH identified in 97 Scandinavian wolf genomes.
Fig. 2: Heterozygosity across the 38 autosomes of 21 Scandinavian wolves.
Fig. 3: Heterozygosity across chromosomes 10–14 in two full siblings and their parents.
Fig. 4: Relationship between F P and F ROH measured with the whole genome in Scandinavian wolves.
Fig. 5: r 2 from regressions of MLH estimated with subsampled SNPs versus MLH calculated from the entire genome.
Fig. 6:  Density of ROH and P values from permutation tests for regions showing a deficit of ROH.

Similar content being viewed by others

References

  1. Saccheri, I. et al. Inbreeding and extinction in a butterfly metapopulation. Nature 392, 491–494 (1998).

    Article  CAS  Google Scholar 

  2. Frankham, R. Genetics and extinction. Biol. Conserv. 126, 131–140 (2005).

    Article  Google Scholar 

  3. Keller, L. F. & Waller, D. M. Inbreeding effects in wild populations. Trends Ecol. Evol. 17, 230–241 (2002).

    Article  Google Scholar 

  4. Fountain, T., Nieminen, M., Sirén, J., Wong, S. C. & Hanski, I. Predictable allele frequency changes due to habitat fragmentation in the Glanville fritillary butterfly. Proc. Natl Acad. Sci. USA 113, 2678–2683 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Charlesworth, D. & Willis, J. H. The genetics of inbreeding depression. Nat. Rev. Genet. 10, 783–796 (2009).

    Article  CAS  PubMed  Google Scholar 

  6. Hedrick, P. W. & Garcia-Dorado, A. Understanding inbreeding depression, purging, and genetic rescue. Trends Ecol. Evol. 31, 940–952 (2016).

    Article  PubMed  Google Scholar 

  7. Kardos, M., Taylor, H. R., Ellegren, H., Luikart, G. & Allendorf, F. W. Genomics advances the study of inbreeding depression in the wild. Evol. Appl. 9, 1205–1218 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  8. Malécot, G. The Mathematics of Heredity (Freeman, San Francisco, 1969).

  9. Wright, S. Coefficients of inbreeding and relationship. Am. Nat. 56, 330–338 (1922).

    Article  Google Scholar 

  10. Pemberton, J. M. Wild pedigrees: the way forward. Proc. R. Soc. B 275, 613–621 (2008).

    Article  CAS  Google Scholar 

  11. Taylor, H. R., Kardos, M. D., Ramstad, K. M. & Allendorf, F. W. Valid estimates of individual inbreeding coefficients from marker-based pedigrees are not feasible in wild populations with low allelic diversity. Conserv. Genet. 16, 901–913 (2015).

    Article  Google Scholar 

  12. Franklin, I. The distribution of the proportion of the genome which is homozygous by descent in inbred individuals. Theor. Popul. Biol. 11, 60–80 (1977).

    Article  CAS  PubMed  Google Scholar 

  13. Hedrick, P. W., Kardos, M., Peterson, R. O. & Vucetich, J. A. Genomic variation of inbreeding and ancestry in the remaining two Isle Royale wolves. J. Hered. 108, 120–126 (2017).

    PubMed  Google Scholar 

  14. Knief, U., Kempenaers, B. & Forstmeier, W. Meiotic recombination shapes precision of pedigree- and marker-based estimates of inbreeding. Heredity 118, 239–248 (2017).

    Article  CAS  PubMed  Google Scholar 

  15. Forstmeier, W., Schielzeth, H., Mueller, J. C., Ellegren, H. & Kempenaers, B. Heterozygosity–fitness correlations in zebra finches: microsatellite markers can be better than their reputation. Mol. Ecol. 21, 3237–3249 (2012).

    Article  PubMed  Google Scholar 

  16. Fisher, R. A. The Theory of Inbreeding 2nd edn (Academic, New York, 1965).

  17. Wang, J. Pedigrees or markers: which are better in estimating relatedness and inbreeding coefficient? Theor. Popul. Biol. 107, 4–13 (2016).

    Article  PubMed  Google Scholar 

  18. Leary, R. F., Allendorf, F. W. & Knudsen, K. L. Developmental stability and enzyme heterozygosity in rainbow trout. Nature 301, 71–72 (1983).

    Article  CAS  PubMed  Google Scholar 

  19. Pierce, B. A. & Mitton, J. B. Allozyme heterozygosity and growth in the tiger salamander, Ambystoma tigrinum. J. Hered. 73, 250–253 (1982).

    Article  CAS  PubMed  Google Scholar 

  20. Coltman, D. W., Pilkington, J. G., Smith, J. A. & Pemberton, J. M. Parasite-mediated selection against inbred Soay sheep in a free-living, island population. Evolution 53, 1259–1267 (1999).

    PubMed  Google Scholar 

  21. Slate, J. et al. Understanding the relationship between the inbreeding coefficient and multilocus heterozygosity: theoretical expectations and empirical data. Heredity 93, 255–265 (2004).

    Article  CAS  PubMed  Google Scholar 

  22. Miller, J. M. et al. Estimating genome-wide heterozygosity: effects of demographic history and marker type. Heredity 112, 240–247 (2014).

    Article  CAS  PubMed  Google Scholar 

  23. Balloux, F., Amos, W. & Coulson, T. Does heterozygosity estimate inbreeding in real populations? Mol. Ecol. 13, 3021–3031 (2004).

    Article  CAS  PubMed  Google Scholar 

  24. Szulkin, M., Bierne, N. & David, P. Heterozygosity–fitness correlations: a time for reappraisal. Evolution 64, 1202–1217 (2010).

    PubMed  Google Scholar 

  25. Huisman, J., Kruuk, L. E. B., Ellis, P. A., Clutton-Brock, T. & Pemberton, J. M. Inbreeding depression across the lifespan in a wild mammal population. Proc. Natl Acad. Sci. USA 113, 3585–3590 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Chen, N., Cosgrove, E. J., Bowman, R., Fitzpatrick, J. W. & Clark, A. G. Genomic consequences of population decline in the endangered Florida scrub-jay. Curr. Biol. 26, 2974–2979 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Kardos, M., Luikart, G. & Allendorf, F. W. Measuring individual inbreeding in the age of genomics: marker-based measures are better than pedigrees. Heredity 115, 63–72 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Hoffman, J. I. et al. High-throughput sequencing reveals inbreeding depression in a natural population. Proc. Natl Acad. Sci. USA 111, 3775–3780 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Kardos, M., Qvarnström, A. & Ellegren, H. Inferring individual inbreeding and demographic history from segments of identity by descent in Ficedula flycatcher genome sequences. Genetics 205, 1319–1334 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  30. Åkesson, M. et al. Genetic rescue in a severely inbred wolf population. Mol. Ecol. 25, 4745–4756 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  31. Bensch, S. et al. Selection for heterozygosity gives hope to a wild population of inbred wolves. PLoS ONE 1, e72 (2006).

    Article  PubMed  PubMed Central  Google Scholar 

  32. Flagstad, Ø. et al. Two centuries of the Scandinavian wolf population: patterns of genetic variability and migration during an era of dramatic decline. Mol. Ecol. 12, 869–880 (2003).

    Article  CAS  PubMed  Google Scholar 

  33. Vilà, C. et al. Rescue of a severely bottlenecked wolf (Canis lupus) population by a single immigrant. Proc. R. Soc. B 270, 91–97 (2003).

    Article  Google Scholar 

  34. Liberg, O. et al. Severe inbreeding depression in a wild wolf (Canis lupus) population. Biol. Lett. 1, 17–20 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Haglund, B. De stora rovdjurens vintervanor II. Viltrevy 5, 213–361 (1969).

    Google Scholar 

  36. Wabakken, P., Sand, H., Liberg, O. & Bjärvall, A. The recovery, distribution, and population dynamics of wolves on the Scandinavian peninsula, 1978–1998. Can. J. Zool. 79, 710–725 (2001).

    Article  Google Scholar 

  37. Seddon, J. M., Sundqvist, A. K., Björnerfeldt, S. & Ellegren, H. Genetic identification of immigrants to the Scandinavian wolf population. Conserv. Genet. 7, 225–230 (2006).

    Article  Google Scholar 

  38. Szpiech, Z. A. et al. Long runs of homozygosity are enriched for deleterious variation. Am. J. Hum. Genet. 93, 90–102 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Thompson, E. A. Identity by descent: variation in meiosis, across genomes, and in populations. Genetics 194, 301–326 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. García-Dorado, A. Understanding and predicting the fitness decline of shrunk populations: inbreeding, purging, mutation, and standard selection. Genetics 190, 1461–1476 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  41. Crow, J. F. & Kimura, M. An Introduction to Population Genetics Theory (The Blackburn Press, Caldwell, 1970).

  42. Kardos, M., Allendorf, F. W. & Luikart, G. Evaluating the role of inbreeding depression in heterozygosity–fitness correlations: how useful are tests for identity disequilibrium? Mol. Ecol. Resour. 14, 519–530 (2014).

    Article  PubMed  Google Scholar 

  43. Pemberton, T. J. et al. Genomic patterns of homozygosity in worldwide human populations. Am. J. Hum. Genet. 91, 275–292 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Hedrick, P. W., Hellsten, U. & Grattapaglia, D. Examining the cause of high inbreeding depression: analysis of whole-genome sequence data in 28 selfed progeny of Eucalyptus grandis. New Phytol. 209, 600–611 (2016).

    Article  CAS  PubMed  Google Scholar 

  45. Bérénos, C., Ellis, P. A., Pilkington, J. G. & Pemberton, J. M. Genomic analysis reveals depression due to both individual and maternal inbreeding in a free-living mammal population. Mol. Ecol. 25, 3152–3168 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  46. McQuillan, R. et al. Runs of homozygosity in European populations. Am. J. Hum. Genet. 83, 359–372 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Chapron, G. et al. Recovery of large carnivores in Europe’s modern human-dominated landscapes. Science 346, 1517–1519 (2014).

    Article  CAS  PubMed  Google Scholar 

  48. Laikre, L., Olsson, F., Jansson, E., Hossjer, O. & Ryman, N. Metapopulation effective size and conservation genetic goals for the Fennoscandian wolf (Canis lupus) population. Heredity 117, 279–289 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Chapron, G. et al. Estimating wolf (Canis lupus) population size from number of packs and an individual based model. Ecol. Model. 339, 33–44 (2016).

    Article  Google Scholar 

  50. Li, H. & Durbin, R. Fast and accurate short read alignment with Burrows–Wheeler transform. Bioinformatics 25, 1754–1760 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Li, H. et al. The sequence alignment/map format and SAMtools. Bioinformatics 25, 2078–2079 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. McKenna, A. et al. The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res. 20, 1297–1303 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Danecek, P. et al. The variant call format and VCFtools. Bioinformatics 27, 2156–2158 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Campbell, C. L., Bhérer, C., Morrow, B. E., Boyko, A. R. & Auton, A. A pedigree-based map of recombination in the domestic dog genome. G3 6, 3517–3524 (2016).

    Article  CAS  Google Scholar 

  55. Sargolzaei, M., Iwaisaki, H. & Colleau, J. J. A fast algorithm for computing inbreeding coefficients in large populations. J. Anim. Breed. Genet. 122, 325–331 (2005).

    Article  CAS  PubMed  Google Scholar 

  56. Kalinowski, S. T., Taper, M. L. & Marshall, T. C. Revising how the computer program CERVUS accommodates genotyping error increases success in paternity assignment. Mol. Ecol. 16, 1099–1106 (2007).

Download references

Acknowledgements

Financial support was obtained from the Swedish Research Council, Swedish Research Council Formas, Swedish Environmental Protection Agency, Research Council of Norway, Norwegian Environment Agency and Marie-Claire Cronstedts Foundation. We thank the National Veterinary Institute (Sweden), Norwegian Institute for Nature Research, Swedish Museum of Natural History, County Administrative Boards in Sweden, Wildlife Damage Centre at the Swedish University of Agricultural Sciences and Inland Norway University of Applied Sciences for contributing with samples. The preparation of samples was conducted by A. Danielsson and E. Hedmark at Grimsö Wildlife Research Station at the Swedish University of Agricultural Sciences. Bioinformatic computations were performed on resources provided by the Swedish National Infrastructure for Computing through the Uppsala Multidisciplinary Center for Advanced Computational Science.

Author information

Authors and Affiliations

Authors

Contributions

H.E. conceived the project. M.K., M.Å., Ø.F., H.S., C.W. and H.E. initiated the project. H.E., M.K. and M.Å. designed the project. M.K. and T.F. performed the data analysis. O.L. performed the original reconstruction of the pedigree. O.L., M.Å. and Ø.F. maintained, updated and refined the pedigree. M.Å. performed the calculations of F P. O.L., H.S., P.W. and C.W. coordinated the field work and sampling. P.O. performed the variant calling. The first draft of the paper was written by M.K. with input from H.E. and T.F. All authors contributed to discussing the results and editing the paper.

Corresponding author

Correspondence to Hans Ellegren.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Additional information

Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Supplementary Information

Supplementary tables and figures.

Life Sciences Reporting Summary

Supplementary Data

Detailed plots of heterozygosity and identified ROH are provided for each chromosome in each of the individuals sampled.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kardos, M., Åkesson, M., Fountain, T. et al. Genomic consequences of intensive inbreeding in an isolated wolf population. Nat Ecol Evol 2, 124–131 (2018). https://doi.org/10.1038/s41559-017-0375-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41559-017-0375-4

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing