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Demographic history, selection and functional diversity of the canine genome

Key Points

  • The dog is descended from a single species, the grey wolf, but from an ancient lineage that is now extinct and is the only large carnivore ever to be domesticated.

  • Dogs were domesticated by hunter-gatherers over 15,000 years ago, whereas all other domesticated species were domesticated by agrarian societies.

  • The demographic history of the dog is complex, with multiple population bottlenecks associated with domestication and breed formation as well as admixture among dog populations and with wolves.

  • DNA analysis from modern dogs can be used to recapitulate the historic migration of human populations, providing previously unknown information about how various regions were settled.

  • Whole-genome sequencing of modern dogs has generated a large catalogue that captures much of the variation that exists in modern dogs.

  • There are nearly 400 breeds of dog worldwide that display an extraordinary amount of phenotypic diversity in terms of morphology, behaviour, and disease susceptibility. All domesticated dogs are members of the same species, termed Canis lupus familiaris or, alternatively, Canis familiaris.

  • Selection for behaviour and appearance in modern breeds has resulted in an increased level of disease susceptibility, perhaps as deleterious alleles 'hitch-hike' with those that breeders and fanciers select for.

  • Cancer is an extremely common disease in dogs, and findings from breed-specific studies reveal information that is relevant for basic cancer biology.

Abstract

The domestic dog represents one of the most dramatic long-term evolutionary experiments undertaken by humans. From a large wolf-like progenitor, unparalleled diversity in phenotype and behaviour has developed in dogs, providing a model for understanding the developmental and genomic mechanisms of diversification. We discuss pattern and process in domestication, beginning with general findings about early domestication and problems in documenting selection at the genomic level. Furthermore, we summarize genotype–phenotype studies based first on single nucleotide polymorphism (SNP) genotyping and then with whole-genome data and show how an understanding of evolution informs topics as different as human history, adaptive and deleterious variation, morphological development, ageing, cancer and behaviour.

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Figure 1: Analytical approach to correct for demographic history in selection scans.
Figure 2: Phenotypic diversity of dog breeds.
Figure 3: Migration of the Fonni's Dog mimics human population migration.
Figure 4: Selective sweeps from whole-genome sequencing analysis.
Figure 5: Haplotype sharing between breeds indicates the source of a common phenotype for a given trait.

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Acknowledgements

We gratefully acknowledge the many individuals who provided comments and edits for this paper. We thank Dayna Dreger, Heidi Parker and Andrew Hogan for providing figures and valuable suggestions. E.A.O. and B.W.D. are supported by the Intramural Program of the US National Human Genome Research Institute. B.W.D. also acknowledges support from Texas A&M University. R.K.W. acknowledges support from the US National Science Foundation grants DEB 1021397 and 1257716 and seminal insights from John Novembre, Kirk Lohmueller and Claire Marsden, all of which have greatly enhanced this perspective on canine evolution.

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Glossary

Population bottlenecks

Reduction in the size of a population due to any of a variety of factors (for example, natural disasters, disease or human intervention) that in turn reduces genetic variation in the population.

Haplotype

A group of variants or markers on a chromosome that are inherited together from one generation to the next. It can also refer to a pattern of variation observed across members of a population.

Linkage disequilibrium

(LD). Nonrandom association of alleles located at distinct loci; measured by determining if the frequency of two loci co-occurring is higher than expected by chance.

Selective sweep

A decrease in genomic variation surrounding a mutation due to positive selection for the mutation.

Genetic drift

Allele frequency changes in a population due to random mating of members of the population.

Effective population size

(Ne). The number of individuals that contribute equally to inherited genetic variation to the next generation within a given population.

Population subdivision

The relational structure of species with multiple subpopulations that exist either in total isolation or with minimal gene flow between them.

Admixture

The process by which isolated populations initiate previously non-existent gene flow.

Popular-sire effect

A reduction in genetic diversity in a population due to nonrandom and excess mating of a sire with desirable traits.

Genetic load

A reduction in the mean individual fitness of a population due to the presence of deleterious alleles or allelic combinations relative to a genotypically ideal population.

Non-synonymous

A change in DNA sequence that alters the encoded amino acid, thus altering the encoded protein.

Synonymous

A change in DNA sequence which, if it occurs in a coding region, does not alter the resultant amino acid.

Chondrodysplastic

A state of abnormal cartilaginous growth resulting in disproportionate dwarfism. In dogs, this affects only the limbs, with minimal other observed effects.

Identical-by-descent

A haplotype shared between individuals that is inherited from a recent common ancestor without intervening recombination.

Quantitative trait locus

(QTL). A defined region of DNA that correlates with variation in a phenotype. Quantitative traits, by comparison, are phenotypes that vary in degree or presentation due to the joint effects of multiple genes.

Penetrance

The proportion of individuals in a population who display a given phenotype in the presence of a specific genotype.

Introgression

Gene flow from one population or individual into the gene pool of another by repeated crosses between related individuals, resulting in individuals with genetic components from both initial populations.

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Ostrander, E., Wayne, R., Freedman, A. et al. Demographic history, selection and functional diversity of the canine genome. Nat Rev Genet 18, 705–720 (2017). https://doi.org/10.1038/nrg.2017.67

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