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Genomic consequences of intensive inbreeding in an isolated wolf population

Nature Ecology & Evolution volume 2, pages 124–131 (2018)Cite this article

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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.

Small populations are particularly vulnerable to extinction due to demographic stochasticity, reduced genetic variation and inbreeding depression1,2,3,4. Inbreeding (mating between relatives) in small populations can lead to decreased individual fitness and population growth rate, owing to the expression of deleterious recessive alleles and increased homozygosity at loci with heterozygous advantage3,5. While inbreeding depression has long interested biologists, its strength and genetic basis in the wild are still not well understood6,7. A major challenge has been accurately measuring individual inbreeding in natural populations.

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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.

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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.

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Authors and Affiliations

  1. Department of Evolutionary Biology, Evolutionary Biology Centre, Uppsala University, Norbyvägen 18D, SE-752 36, Uppsala, Sweden

    Marty Kardos, Toby Fountain & Hans Ellegren

  2. Flathead Lake Biological Station, University of Montana, Polson, MA, 59860, USA

    Marty Kardos

  3. Department of Ecology, Grimsö Wildlife Research Station, Swedish University of Agricultural Sciences, SE-730 91, Riddarhyttan, Sweden

    Mikael Åkesson, Olof Liberg, Håkan Sand & Camilla Wikenros

  4. Norwegian Institute for Nature Research, PO Box 5685, Sluppen, NO-7485, Trondheim, Norway

    Øystein Flagstad

  5. Wallenberg Advanced Bioinformatics Infrastructure, Science for Life Laboratory, Uppsala University, 75123, Uppsala, Sweden

    Pall Olason

  6. Faculty of Applied Ecology and Agricultural Sciences, Campus Evenstad, Inland Norway University of Applied Sciences, NO-2480, Elverum, Norway

    Petter Wabakken

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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.

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Correspondence to Hans Ellegren.

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Supplementary Data

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

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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

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