Identification of genomic variants putatively targeted by selection during dog domestication
Open accessAbstract
BACKGROUND: Dogs [Canis lupus familiaris] were the first animal species to be domesticated and continue to occupy an important place in human societies. Recent studies have begun to reveal when and where dog domestication occurred. While much progress has been made in identifying the genetic basis of phenotypic differences between dog breeds we still know relatively little about the genetic changes underlying the phenotypes that differentiate all dogs from their wild progenitors, wolves [Canis lupus]. In particular, dogs generally show reduced aggression and fear towards humans compared to wolves. Therefore, selection for tameness was likely a necessary prerequisite for dog domestication. With the increasing availability of whole-genome sequence data it is possible to try and directly identify the genetic variants contributing to the phenotypic differences between dogs and wolves. RESULTS: We analyse the largest available database of genome-wide polymorphism data in a global sample of dogs 69 and wolves 7. We perform a scan to identify regions of the genome that are highly differentiated between dogs and wolves. We identify putatively functional genomic variants that are segregating or at high frequency [> = 0.75 Fst] for alternative alleles between dogs and wolves. A biological pathways analysis of the genes containing these variants suggests that there has been selection on the 'adrenaline and noradrenaline biosynthesis pathway', well known for its involvement in the fight-or-flight response. We identify 11 genes with putatively functional variants fixed for alternative alleles between dogs and wolves. The segregating variants in these genes are strong candidates for having been targets of selection during early dog domestication. CONCLUSIONS: We present the first genome-wide analysis of the different categories of putatively functional variants that are fixed or segregating at high frequency between a global sampling of dogs and wolves. We find evidence that selection has been strongest around non-synonymous variants. Strong selection in the initial stages of dog domestication appears to have occurred on multiple genes involved in the fight-or-flight response, particularly in the catecholamine synthesis pathway. Different alleles in some of these genes have been associated with behavioral differences between modern dog breeds, suggesting an important role for this pathway at multiple stages in the domestication process.
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RNPC3 is one of only two genes with more than one putatively causal variant fixed between dogs and wolves.
“RNPC3 is one of only two genes with more than one putatively causal variant fixed between dogs and wolves (the other is a gene of unknown function) [52].”
From Self-domestication in Homo sapiens: Insights from comparative genomics (2017) · cites this paper as [52]
The most intriguing variant fixed between dogs and wolves is found in the 3'-UTR of SLC9A6.
“One such observation concerns “the most intriguing variant fixed between dogs and wolves” [52], which is found in the 3’-UTR of SLC9A6.”
From Self-domestication in Homo sapiens: Insights from comparative genomics (2017) · cites this paper as [52]
Loss-of-function mutations in SLC9A6 in humans can lead to Christianson syndrome, also known as Angelman-like syndrome.
“Cagan and Blass [52] note that loss-of-function mutations in this gene in humans can lead to Christianson syndrome, also known as “Angelman-like syndrome”.”
From Self-domestication in Homo sapiens: Insights from comparative genomics (2017) · cites this paper as [52]
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- Authors
- Cagan, A., & Blass, T.
- Affiliations
- Max Planck Institute for Evolutionary Anthropology (DE)
- Corresponding author
- Cagan, Alex
- ORCID
- Cagan, Alex
- Venue
- BMC Evolutionary Biology
- Published
- 2016-01-12
- Volume
- 16
- Issue
- 1
- Pages
- 10-10
- ISSN
- 1471-2148 (ISSN-L)
- PMC
- PMC4710014
- OpenAlex
- W2233881958
- Cited by
- 69
- References
- 84
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 5 · 2023: 7 · 2022: 14 · 2021: 10 · 2020: 3 · 2019: 5 · 2018: 10 · 2017: 5 · 2016: 3
- FWCI
- 6.19
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- BMC Evolutionary Biology (publishedVersion)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion, cc-by)
- Max Planck Digital Library (submittedVersion, other-oa)
- Funders
- Max-Planck-Gesellschaft
- 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 › Genetics › Genetic diversity and population structure
- Keywords
- dog domestication, dogs, wolf, genomic signatures of selection, non-synonymous variants, fight-or-flight response, tameness, fear of humans
- MeSH terms
- Animals, Animals, Domestic, Breeding, Dogs, Humans, Phenotype, Selection, Genetic, Genetic Variation, Wolves
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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