To identify genetic changes underlying dog domestication and reconstruct their early evolutionary history, we generated high-quality genome sequences from three gray wolves, one from each of the three putative centers of dog domestication, two basal dog lineages (Basenji and Dingo) and a golden jackal as an outgroup. Analysis of these sequences supports a demographic model in which dogs and wolves diverged through a dynamic process involving population bottlenecks in both lineages and post-divergence gene flow. In dogs, the domestication bottleneck involved at least a 16-fold reduction in population size, a much more severe bottleneck than estimated previously. A sharp bottleneck in wolves occurred soon after their divergence from dogs, implying that the pool of diversity from which dogs arose was substantially larger than represented by modern wolf populations. We narrow the plausible range for the date of initial dog domestication to an interval spanning 11–16 thousand years ago, predating the rise of agriculture. In light of this finding, we expand upon previous work regarding the increase in copy number of the amylase gene (AMY2B) in dogs, which is believed to have aided digestion of starch in agricultural refuse. We find standing variation for amylase copy number variation in wolves and little or no copy number increase in the Dingo and Husky lineages. In conjunction with the estimated timing of dog origins, these results provide additional support to archaeological finds, suggesting the earliest dogs arose alongside hunter-gathers rather than agriculturists. Regarding the geographic origin of dogs, we find that, surprisingly, none of the extant wolf lineages from putative domestication centers is more closely related to dogs, and, instead, the sampled wolves form a sister monophyletic clade. This result, in combination with dog-wolf admixture during the process of domestication, suggests that a re-evaluation of past hypotheses regarding dog origins is necessary. The process of dog domestication is still poorly understood, largely because no studies thus far have leveraged deeply sequenced whole genomes from wolves and dogs to simultaneously evaluate support for the proposed source regions: East Asia, the Middle East, and Europe. To investigate dog origins, we sequence three wolf genomes from the putative centers of origin, two basal dog breeds (Basenji and Dingo), and a golden jackal as an outgroup. We find that none of the wolf lineages from the hypothesized domestication centers is supported as the source lineage for dogs, and that dogs and wolves diverged 11,000–16,000 years ago in a process involving extensive admixture and that was followed by a bottleneck in wolves. In addition, we investigate the amylase (AMY2B) gene family expansion in dogs, which has recently been suggested as being critical to domestication in response to increased dietary starch. We find standing variation in AMY2B copy number in wolves and show that some breeds, such as Dingo and Husky, lack the AMY2B expansion. This suggests that, at the beginning of the domestication process, dogs may have been characterized by a more carnivorous diet than their modern day counterparts, a diet held in common with early hunter-gatherers.

Dog Domestication: The precise details of the domestication and origins of domestic dogs are unclear. Thalmann et al. (p. 871 ; see the cover) analyzed complete mitochondrial genomes from present-day dogs and wolves, as well as 18 fossil canids dating from 1000 to 36,000 years ago from the Old and New Worlds. The data suggest that an ancient, now extinct, central European population of wolves was directly ancestral to domestic dogs. Furthermore, several ancient dogs may represent failed domestication events.

Controlling for background demographic effects is important for accurately identifying loci that have recently undergone positive selection. To date, the effects of demography have not yet been explicitly considered when identifying loci under selection during dog domestication. To investigate positive selection on the dog lineage early in the domestication, we examined patterns of polymorphism in six canid genomes that were previously used to infer a demographic model of dog domestication. Using an inferred demographic model, we computed false discovery rates (FDR) and identified 349 outlier regions consistent with positive selection at a low FDR. The signals in the top 100 regions were frequently centered on candidate genes related to brain function and behavior, including LHFPL3, CADM2, GRIK3, SH3GL2, MBP, PDE7B, NTAN1, and GLRA1. These regions contained significant enrichments in behavioral ontology categories. The 3^rd top hit, CCRN4L, plays a major role in lipid metabolism, that is supported by additional metabolism related candidates revealed in our scan, including SCP2D1 and PDXC1. Comparing our method to an empirical outlier approach that does not directly account for demography, we found only modest overlaps between the two methods, with 60% of empirical outliers having no overlap with our demography-based outlier detection approach. Demography-aware approaches have lower-rates of false discovery. Our top candidates for selection, in addition to expanding the set of neurobehavioral candidate genes, include genes related to lipid metabolism, suggesting a dietary target of selection that was important during the period when proto-dogs hunted and fed alongside hunter-gatherers. Identification of the genomic regions under selection during dog domestication is extremely challenging because the demographic fluctuations associated with domestication can produce signals in polymorphism data that mimic those imposed by selective sweeps. We perform the first analysis of selection on the dog lineage that explicitly incorporates a demographic model, that by controlling for the rate of false discovery, more robustly identifies targets of selection. To do so, we conduct a selection scan using three wolf genomes representing the putative centers of dog domestication, two basal dog breeds (Basenji and Dingo), and a golden jackal as outgroup, for which we previously inferred a demographic model. We find that our demographically informed analyses filters out many signals that would be otherwise classified as putative selection signals under an empirical outlier approach. We identify 68 regions of the genome that have likely experienced positive selection. Besides identifying a number of new neurobehavioral candidate genes, our candidate regions contain genes related to lipid metabolism, including CCRN4L, which is centered in the 3^rd ranked region. This suggests a previously unreported locus of dietary adaptation, potentially due to the change in diet composition as hunting efficiency increased when proto dogs began hunting alongside hunter-gatherers.