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Identification of Genomic Variants Putatively Targeted by Selection During Dog Domestication


Identification of Genomic Variants Putatively Targeted by Selection During Dog Domestication

Alex Cagan et al. BMC Evol Biol.


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.


Fig. 1
Fig. 1
Genome-wide scan for selective sweeps. Z-transformed mean Fst calculated in 500kb genomic windows across the autosomes and X chromosome between dogs and wolves. Each point represents a 500kb window. A dashed horizontal line represents our threshold for identifying putatively selected regions (>5 Z(Fst)). 18 windows exceed this threshold and are considered as putative selective sweeps
Fig. 2
Fig. 2
Percentage of functional sites in discrete Fst bins. Polymorphic sites and substitutions were ordered into bins based on their Fst score. For each bin sites were categorized according to their putative function. The number of sites in each functional category are plotted as a percentage of the total sites in that bin. Values at top refer to total number of sites in each bin. Synonymous sites, which are assumed to be selectively neutral, decline as a percentage of total sites as the Fst score of the bin increases. In contrast, we observe an increase in the percentage of several categories functional sites in the top bins [0.95–1, 1]. This may be the result of positive selection raising these variants to high frequency and fixation
Fig. 3
Fig. 3
Distribution of mean Fst in 50kb windows centered around putatively functional sites. Polymorphic sites with Fst > =0.75 between dogs and wolves were classified according to their putative function. For each putatively functional site the mean Fst was calculated in a 50kb window centered on the site. A violin plot shows the distribution of mean Fst values for each category of functional site (5‘-UTR, 3‘-UTR, non-synonymous, splice site, stop gained, synonymous). Synonymous mutations were included as a category to show the expectation in the absence of positive selection

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