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MBE Advance Access published online on August 9, 2008
Molecular Biology and Evolution, 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 Article

The legacy of domestication: Accumulation of deleterious mutations in the dog genome

Fernando Cruz1, Carles Vilà2,3 and Matthew T. Webster4

1 Department of Ecology and Evolution, Biophore, University of Lausanne, 1015 Lausanne, Switzerland
2 Department of Evolution, Genomics and Systematics, Evolutionary Biology Centre, Uppsala University, Norbyvägen 18D, 75236 Uppsala, Sweden
3 Estación Biológica de Doñana-CSIC, Avd. María Luisa s/n, 41013 Seville, Spain
4 Department of Medical Biochemistry and Microbiology, Uppsala University, Box 597, SE-751 24 Uppsala, Sweden

Correspondence should be addressed to: Matthew Webster, Tel: +46 18 471 4525. Fax: +46 18 471 4673. matthew.webster{at}imbim.uu.se

Received for publication July 14, 2008. 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 grey wolf. We compared variation in dog and wolf genes using whole genome 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 non-functional 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


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