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MBE Advance Access originally published online on August 9, 2008
Molecular Biology and Evolution 2008 25(11):2331-2336; doi:10.1093/molbev/msn177
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© The Author 2008. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Research Articles

The Legacy of Domestication: Accumulation of Deleterious Mutations in the Dog Genome

Fernando Cruz*, Carles Vilà{dagger},{ddagger} and Matthew T. Webster§

* Department of Ecology and Evolution, Biophore, University of Lausanne, Lausanne, Switzerland
{dagger} Department of Evolution, Genomics and Systematics, Evolutionary Biology Centre, Uppsala University, Norbyvägen, Uppsala, Sweden
{ddagger} Estación Biológica de Doñana-Consejo Superior de Investigaciones Científicas (CSIC), Avd. María Luisa s/n, 41013 Seville, Spain
§ Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden

E-mail: matthew.webster{at}imbim.uu.se.

Accepted for publication August 1, 2008.

Dogs exhibit more phenotypic variation than any other mammal and are affected by a wide variety of genetic diseases. However, the origin and genetic basis of this variation is still poorly understood. We examined the effect of domestication on the dog genome by comparison with its wild ancestor, the gray wolf. We compared variation in dog and wolf genes using whole-genome single nucleotide polymorphism (SNP) data. The dN/dS ratio ({omega}) was around 50% greater for SNPs found in dogs than in wolves, indicating that a higher proportion of nonsynonymous alleles segregate in dogs compared with nonfunctional genetic variation. We suggest that the majority of these alleles are slightly deleterious and that two main factors may have contributed to their increase. The first is a relaxation of selective constraint due to a population bottleneck and altered breeding patterns accompanying domestication. The second is a reduction of effective population size at loci linked to those under positive selection due to Hill–Robertson interference. An increase in slightly deleterious genetic variation could contribute to the prevalence of disease in modern dog breeds.

Key Words: genetic drift • bottleneck • selective constraint • purifying selection • domestication • dog genome

John H McDonald, Associate Editor


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