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The genomic signature of dog domestication reveals adaptation to a starch-rich diet

Journal name:
Nature
Year published:
(2013)
DOI:
doi:10.1038/nature11837
Received
Accepted
Published online

The domestication of dogs was an important episode in the development of human civilization. The precise timing and location of this event is debated1, 2, 3, 4, 5 and little is known about the genetic changes that accompanied the transformation of ancient wolves into domestic dogs. Here we conduct whole-genome resequencing of dogs and wolves to identify 3.8 million genetic variants used to identify 36 genomic regions that probably represent targets for selection during dog domestication. Nineteen of these regions contain genes important in brain function, eight of which belong to nervous system development pathways and potentially underlie behavioural changes central to dog domestication6. Ten genes with key roles in starch digestion and fat metabolism also show signals of selection. We identify candidate mutations in key genes and provide functional support for an increased starch digestion in dogs relative to wolves. Our results indicate that novel adaptations allowing the early ancestors of modern dogs to thrive on a diet rich in starch, relative to the carnivorous diet of wolves, constituted a crucial step in the early domestication of dogs.

At a glance

  1. Figure 1: Selection analyses identified 36 candidate domestication regions.
    Selection analyses identified 36 candidate domestication regions.

    a, Distribution of Z-transformed average pooled heterozygosity in dog (Z(HP)DOG) and wolf (Z(HP)WOLF) respectively, as well as average fixation index (Z(FST)), for autosomal 200kb windows (σ, standard deviation; μ, average). b, The positive end of the Z(FST) distribution plotted along dog autosomes 1–38 (chromosomes are separated by colour). A dashed horizontal line indicates the cut-off (Z>5) used for extracting outliers. c, The negative end of the Z(HP) distribution plotted along dog autosomes 1–38. A dashed horizontal line indicates the cut-off (Z<−5) used for extracting outliers.

  2. Figure 2: Selection for increased amylase activity.
    Selection for increased amylase activity.

    a, Pooled heterozygosity, HP (blue), and average fixation index, FST (orange), plotted for 200-kb windows across a chromosome 6 region harbouring AMY2B. b, Heterozygosity, H (blue), and fixation index, FST (orange), for single SNPs in the selected region. Dog relative to wolf coverage, rC (green line), indicates increase in AMY2B copy number in dog. Genes in the region are shown below panel b. c, Histogram showing the distribution of diploid amylase copy number in wolf (n = 35) (blue) and dog (n = 136) (red). d, Amylase messenger RNA expression levels in pancreas of wolf (n = 12) and dog (n = 9). e, Amylase activity in serum from wolf (n = 13) and dog (n = 12).

  3. Figure 3: Selection is associated with increased maltase activity.
    Selection is associated with increased maltase activity.

    a, Pooled heterozygosity, HP (blue), and average fixation index, FST (orange), plotted for 200-kb windows across a chromosome 16 region harbouring MGAM. b, Heterozygosity, H (blue), and fixation index, FST (orange), for single SNPs in the selected region. c, Haplotypes inferred from genotyping of 47 SNPs across the MGAM locus in 71 dogs and 19 wolves (red and blue colour are major and minor dog allele, respectively). Genes in the genotyped region are shown below panel c. d, MGAM mRNA expression levels in pancreas of wolf (n = 8) and dog (n = 9). e, MGAM activity in serum from wolf (n = 8) and dog (n = 7).

Accession codes

Primary accessions

Sequence Read Archive

Author information

Affiliations

  1. Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala University, 75237 Uppsala, Sweden

    • Erik Axelsson,
    • Abhirami Ratnakumar,
    • Maja-Louise Arendt,
    • Khurram Maqbool,
    • Matthew T. Webster &
    • Kerstin Lindblad-Toh
  2. Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts 02139, USA

    • Michele Perloski &
    • Kerstin Lindblad-Toh
  3. Grimsö Wildlife Research Station, Department of Ecology, Swedish University of Agricultural Sciences, 73091 Riddarhyttan, Sweden

    • Olof Liberg
  4. Department of Forestry and Wildlife Management, Faculty of Applied Ecology and Agricultural Sciences, Hedmark University College, Campus Evenstad, NO-2418 Elverum, Norway

    • Jon M. Arnemo
  5. Department of Wildlife, Fish and Environmental Studies, Faculty of Forest Sciences, Swedish University of Agricultural Sciences, 901 83 Umeå, Sweden

    • Jon M. Arnemo
  6. Science for Life Laboratory, Department of Clinical Sciences, Swedish University of Agricultural Sciences, 75651 Uppsala, Sweden

    • Åke Hedhammar

Contributions

K.L.-T. and Å.H. designed the study. K.L.-T. and E.A. oversaw the study. M.-L.A. coordinated and performed the majority of the sample collecting and O.L. and J.M.A. provided samples of critical importance. E.A. performed the SNP detection and selection analyses; A.R. identified candidate causative mutations and analysed haplotypes in CDRs; K.M. detected CNVs bioinformatically; M.T.W. performed phylogenetic analysis and analysed the Canine HD-array data; A.R. performed the maltase activity assay; M.-L.A. validated CNVs and quantified mRNA expression of candidate genes; M.P. performed validation SNP genotyping; E.A., A.R., M.-L.A. and K.L-T. interpreted the data; E.A. and K.L.-T. wrote the paper with input from the other authors.

Competing financial interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to:

Sequence reads are available under the accession number SRA061854 (NCBI Sequence Read Archive).

Author Details

Supplementary information

PDF files

  1. Supplementary Information (6.4M)

    This file contains Supplementary Discussions sections 1-9, Supplementary references, Supplementary Figures 1-24 and Supplementary Tables 1-25.

Zip files

  1. Supplementary Data 1 (3.4M)

    This zipped file lists the position of short indels in the canine genome.

  2. Supplementary Data 2 (257K)

    This zipped file lists the position of CNVs in the canine genome.

Additional data

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