Genome sequence, comparative analysis and haplotype structure of the domestic dog
Open accessAbstract
Here we report a high-quality draft genome sequence of the domestic dog (Canis familiaris), together with a dense map of single nucleotide polymorphisms (SNPs) across breeds. The dog is of particular interest because it provides important evolutionary information and because existing breeds show great phenotypic diversity for morphological, physiological and behavioural traits. We use sequence comparison with the primate and rodent lineages to shed light on the structure and evolution of genomes and genes. Notably, the majority of the most highly conserved non-coding sequences in mammalian genomes are clustered near a small subset of genes with important roles in development. Analysis of SNPs reveals long-range haplotypes across the entire dog genome, and defines the nature of genetic diversity within and across breeds. The current SNP map now makes it possible for genome-wide association studies to identify genes responsible for diseases and traits, with important consequences for human and companion animal health.
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The isolation of strains and breeds in mouse, rat, cow, and dog results in much longer block lengths than are found in humans.
“The isolation of strains and breeds in these species results in much longer block lengths than are found in humans.”
From Linkage disequilibrium--understanding the evolutionary past and mapping the medical future. (2008) · cites this paper as [24]
The dog haplotype analysis (section labelled “see section ‘Resolving canid phylogeny’”; page unavailable) reports that linkage disequilibrium within dog breeds extends several megabases, compared with a rapid decline in the human population, and links the dog pattern to breed-creation bottlenecks. It does not establish longer haplotype blocks for mouse, rat, or cow. It also reports that ancestral dog haplotype blocks are shorter than human blocks, so the supported comparison is specifically long-range linkage disequilibrium within breeds, not a blanket comparison of block lengths. (LLM, conf=0.85)
Experimental — accuracy not yet measuredDogs were domesticated from grey wolves at least 15 000-50 000 years ago, through both natural and artificial selection.
“Dogs were domesticated from grey wolves at least 15 000–50 000 years ago, through both natural and artificial selection [16,17].”
From Are dark-eyed dogs favoured by humans? Domestication as a potential driver of iris colour difference between dogs and wolves (2023) · cites this paper as [16]
The Abstract says dogs were domesticated from grey wolves at least 15,000 years ago, possibly as far back as 100,000 years ago, and describes later selective breeding by humans. It does not give 50,000 years as a bound or explicitly attribute domestication to both natural and artificial selection. (LLM, conf=0.86)
Experimental — accuracy not yet measuredThe median synonymous substitution rate (Ks) of 1:1 opossum-human orthologues is 1.02.
“The median value of K S is 1.02.”
From Genome of the marsupial Monodelphis domestica reveals innovation in non-coding sequences (2007) · cites this paper as [10]
Most evolutionarily conserved sequence in eutherian genomes is not protein-coding but consists of conserved non-coding elements.
“The most surprising discovery to emerge from comparative analyses of eutherian genomes is the finding that the majority of evolutionarily conserved sequence does not represent protein-coding genes, but rather are conserved non-coding elements (CNEs) 7,10 .”
From Genome of the marsupial Monodelphis domestica reveals innovation in non-coding sequences (2007) · cites this paper as [10]
The proportion of eutherian-specific CNEs recognizable as transposable-element-derived, 16%, is very similar to the proportion of total aligned sequence between human, mouse and dog recognizable as ancestral transposable elements, about 17% of about 812 Mb, most of which is inactive.
“Strikingly, the proportion of eutherian-specific CNEs recognizable as transposable-element-derived (16%) is very similar to the proportion of the total aligned sequence between the human, mouse and dog genomes recognizable as ancestral transposable elements (,17% of ,812 Mb; the vast majority of which is inactive) 10 .”
From Genome of the marsupial Monodelphis domestica reveals innovation in non-coding sequences (2007) · cites this paper as [10]
The Felis catus genome is predicted to contain 19,493 protein-coding genes and 1,855 noncoding RNAs, similar to dog.
“The Felis catus genome is predicted to contain 19,493 protein-coding genes and 1,855 noncoding RNAs, similar to dog (14).”
From Comparative analysis of the domestic cat genome reveals genetic signatures underlying feline biology and domestication (2014) · cites this paper as [14]
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- Authors
- members, B. S. P., Lindblad-Toh, K., Wade, C. M., Mikkelsen, T. S., Karlsson, E. K., Jaffe, D. B., Kamal, M., Clamp, M., Chang, J. L., Kulbokas, E. J., Zody, M. C., Mauceli, E., Xie, X., Breen, M., Wayne, R. K., Ostrander, E. A., Ponting, C. P., Galibert, F., Smith, D. R., deJong, P. J., Kirkness, E., Alvarez, P., Biagi, T., Brockman, W., Butler, J., Chin, C.-W., Cook, A., Cuff, J., Daly, M. J., DeCaprio, D., Gnerre, S., Grabherr, M., Kellis, M., Kleber, M., Bardeleben, C., Goodstadt, L., Heger, A., Hitte, C., Kim, L., Koepfli, K.-P., Parker, H. G., Pollinger, J. P., Searle, S. M. J., Sutter, N. B., Thomas, R., Webber, C., & Lander, E. S.
- Affiliations
- Broad Institute (US)
- North Carolina State University (US)
- National Institutes of Health (US)
- Centre National de la Recherche Scientifique (FR)
- University of California, Los Angeles (US)
- University of Oxford (GB)
- Corresponding author
- Lander, Eric S.
- ORCID
- Wade, Claire M
- Mikkelsen, Tarjei S.
- Karlsson, Elinor K.
- Jaffe, David B.
- Zody, Michael C.
- Xie, Xiaohui
- Breen, Matthew
- Wayne, Robert K.
- Ostrander, Elaine A.
- Ponting, Chris P.
- Galibert, Francis
- Alvarez, Pablo
- Cuff, James
- Daly, Mark J.
- DeCaprio, David
- Grabherr, Manfred
- Kellis, Manolis
- Heger, Andreas
- Hitte, Christophe
- Kim, Lisa
- Koepfli, Klaus-Peter
- Parker, Heidi G.
- Pollinger, John P.
- Sutter, Nathan B.
- Thomas, Rachael
- Webber, Caleb
- Lander, Eric S.
- Venue
- Nature
- Published
- 2005-12
- Volume
- 438
- Issue
- 7069
- Pages
- 803-819
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2114611642
- Cited by
- 2,568
- References
- 115
- Citations by year
- 2026: 40 · 2025: 66 · 2024: 94 · 2023: 106 · 2022: 95 · 2021: 122 · 2020: 141 · 2019: 122 · 2018: 114 · 2017: 88 · 2016: 116 · 2015: 138 · 2014: 140 · 2013: 131 · 2012: 144
- FWCI
- 84.07
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- ORCA Online Research @Cardiff (Cardiff University) (submittedVersion)
- Funders
- National Institutes of Health
- National Human Genome Research Institute
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Human-Animal Interaction Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and phenotypic traits in livestock
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Keywords
- dogs, single nucleotide polymorphisms, breed genetic diversity, haplotype structure, genome evolution, comparative genomics, conserved non-coding elements, genome-wide association study, dog breeds
- MeSH terms
- Animals, Dog Diseases, Dogs, Female, Haplotypes, Humans, Hybridization, Genetic, Male, Mutagenesis, Genome, Conserved Sequence, Evolution, Molecular, Short Interspersed Nucleotide Elements, Polymorphism, Single Nucleotide, Genomics, Synteny, Mice, Rats
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