Dog breeding promotes within-group homogeneity through conformation to strict breed standards, while simultaneously driving between-group heterogeneity. There are over 350 recognized dog breeds that provide the foundation for investigating the genetic basis of phenotypic diversity. Typically, breed standard phenotypes such as stature, pelage, and craniofacial structure are analyzed through genetic association studies. However, such analyses are limited to assayed phenotypes only, leaving difficult-to-measure phenotypic subtleties easily overlooked. We investigated coding variation from over 2000 dogs, leading to discoveries of variants related to craniofacial morphology and stature. Breed-enriched variants were prioritized according to gene constraint, which was calculated using a mutation model derived from trinucleotide substitution probabilities. Among the newly found variants is a splice-acceptor variant in PDGFRA associated with bifid nose, a characteristic trait of Çatalburun dogs, implicating the gene’s role in midline closure. Two additional LCORL variants, both associated with canine body size are also discovered: a frameshift that causes a premature stop in large breeds (>25 kg) and an intronic substitution found in small breeds (<10 kg), thus highlighting the importance of allelic heterogeneity in selection for breed traits. Most variants prioritized in this analysis are not associated with genomic signatures for breed differentiation, as these regions are enriched for constrained genes intolerant to nonsynonymous variation. This indicates trait selection in dogs is likely a balancing act between preserving essential gene functions and maximizing regulatory variation to drive phenotypic extremes.

The origins and extreme morphological evolution of the modern dog breeds are poorly studied because the founder populations are extinct. Here, we analyse eight 100 to 200 years old dog fur samples obtained from traditional North Swedish clothing, to explore the origin and artificial selection of the modern Nordic Lapphund and Elkhound dog breeds. Population genomic analysis confirmed the Lapphund and Elkhound breeds to originate from the local dog population, and showed a distinct decrease in genetic diversity in agreement with intense breeding. We identified eleven genes under positive selection during the breed development. In particular, the MSRB3 gene, associated with breed-related ear morphology, was selected in all Lapphund and Elkhound breeds, and functional assays showed that a SNP mutation in the 3′UTR region suppresses its expression through miRNA regulation. Our findings demonstrate analysis of near-modern dog artifacts as an effective tool for interpreting the origin and artificial selection of the modern dog breeds.

Background: The international Dog10K project aims to sequence and analyze several thousand canine genomes. Incorporating 20 × data from 1987 individuals, including 1611 dogs (321 breeds), 309 village dogs, 63 wolves, and four coyotes, we identify genomic variation across the canid family, setting the stage for detailed studies of domestication, behavior, morphology, disease susceptibility, and genome architecture and function. Results: We report the analysis of > 48 M single-nucleotide, indel, and structural variants spanning the autosomes, X chromosome, and mitochondria. We discover more than 75% of variation for 239 sampled breeds. Allele sharing analysis indicates that 94.9% of breeds form monophyletic clusters and 25 major clades. German Shepherd Dogs and related breeds show the highest allele sharing with independent breeds from multiple clades. On average, each breed dog differs from the UU_Cfam_GSD_1.0 reference at 26,960 deletions and 14,034 insertions greater than 50 bp, with wolves having 14% more variants. Discovered variants include retrogene insertions from 926 parent genes. To aid functional prioritization, single-nucleotide variants were annotated with SnpEff and Zoonomia phyloP constraint scores. Constrained positions were negatively correlated with allele frequency. Finally, the utility of the Dog10K data as an imputation reference panel is assessed, generating high-confidence calls across varied genotyping platform densities including for breeds not included in the Dog10K collection. Conclusions: We have developed a dense dataset of 1987 sequenced canids that reveals patterns of allele sharing, identifies likely functional variants, informs breed structure, and enables accurate imputation. Dog10K data are publicly available.

Simple Summary This study evaluated the genetic diversity and investigated the origin of Vietnamese domestic dogs on the basis of genetic data. A total of 56 haplotypes (group of genes inherited together from a single parent), including 14 indigenous ones (two of them have not been previously reported) were observed, with some of them implying that Australian dingo and Polynesian dogs originated from Southeast Asian ones, reinforcing the theory of domestication of dogs to the south of the Yangtze River. In this study, samples from 429 dog individuals across three main regions of Vietnam (Southern Vietnam (SVN), Central Vietnam (CVN), and Northern Vietnam (NVN)) were collected to analyze the 582 bp region mtDNA HVI, so as to study the genetic diversity and to screen the rare haplotype E in the Vietnamese village dog population. Nine new haplotypes A, two new haplotypes B, and three haplotypes C were unique to Vietnam dogs, in which the new haplotypes An3, An7, Cn1, and Cn3 concerned mutations at new polymorphism sites (15,517, 15,505, 15,479, and 15,933, respectively) which have not been previously reported. The detection of haplotypes A9 and A29, and the appearance of haplotype A200 in the two individual dogs sampled support that the Southeast Asian dog is the ancestor of today's Australian dingo and Polynesian dog. The two rare haplotypes E (E1 and E4) were reconfirmed in Vietnamese dogs and discussed. This study also contributes to strengthening the theory of domestication of dogs to the south of the Yangtze River and the Southeast Asian origin of the dingo.

Sighthounds, a distinctive group of hounds comprising numerous breeds, have their origins rooted in ancient artificial selection of dogs. In this study, we performed genome sequencing for 123 sighthounds, including one breed from Africa, six breeds from Europe, two breeds from Russia, and four breeds and 12 village dogs from the Middle East. We gathered public genome data of five sighthounds and 98 other dogs as well as 31 gray wolves to pinpoint the origin and genes influencing the morphology of the sighthound genome. Population genomic analysis suggested that sighthounds originated from native dogs independently and were comprehensively admixed among breeds, supporting the multiple origins hypothesis of sighthounds. An additional 67 published ancient wolf genomes were added for gene flow detection. Results showed dramatic admixture of ancient wolves in African sighthounds, even more than with modern wolves. Whole-genome scan analysis identified 17 positively selected genes (PSGs) in the African population, 27 PSGs in the European population, and 54 PSGs in the Middle Eastern population. None of the PSGs overlapped in the three populations. Pooled PSGs of the three populations were significantly enriched in "regulation of release of sequestered calcium ion into cytosol"(gene ontology: 0051279), which is related to blood circulation and heart contraction. In addition, ESR1, JAK2, ADRB1, PRKCE, and CAMK2D were under positive selection in all three selected groups. This suggests that different PSGs in the same pathway contributed to the similar phenotype of sighthounds. We identified an ESR1 mutation (chr1: g.42,177,149-T > C) in the transcription factor (TF) binding site of Stat5a and a JAK2 mutation (chr1: g.93,277,007-T > A) in the TF binding site of Sox5. Functional experiments confirmed that the ESR1 and JAK2 mutation reduced their expression. Our results provide new insights into the domestication history and genomic basis of sighthounds.

Research on the genetics of domestication most often focuses on the protein-coding exons. However, exons cover only a minor part (1-2%) of the canine genome, whereas functional mutations may be located also in regions beyond the exome, in regulatory regions. Therefore, a large proportion of phenotypical differences between dogs and wolves may remain genetically unexplained. In this study, we identified variants that have high allelic frequency differences (i.e., highly differentiated variants) between wolves and dogs across the canine genome and investigated the potential functionality. We found that the enrichment of highly differentiated variants was substantially higher in promoters than in exons and that such variants were enriched also in enhancers. Several enriched pathways were identified including oxytocin signaling, carbohydrate digestion and absorption, cancer risk, and facial and body features, many of which reflect phenotypes of potential importance during domestication, including phenotypes of the domestication syndrome. The results highlight the importance of regulatory mutations during dog domestication and motivate the functional annotation of the noncoding part of the canine genome.

The dog population of Southern East Asia is unique in harboring virtually the full range of the universal mtDNA gene pool, and consequently, it has the highest genetic diversity worldwide. Despite this, limited research has been performed on dog genetics within this region. Here we present the first comprehensive study of a sub-region within Southern East Asia, analyzing 528 bp of mtDNA for 265 dogs from Thailand, in the context of dogs from across the Old World. We found that Thailand was the only region in the world that has the full range of the universal mtDNA gene pool, that is, all 10 sub-haplogroups. Consequently, the statistics for diversity are among the highest, especially in North Thailand, which had high values for haplotype diversity and the number of haplotypes, and the lowest proportion of individuals with a universal type-derived haplotype (UTd) among all regions. As previously observed, genetic diversity is distinctly lower outside Southern East Asia and it decreases following a cline to the lowest values in western Eurasia. Thus, the limited geographical region of Thailand harbors a distinctly higher genetic diversity than much larger regions in western Eurasia, for example, Southwest Asia and Europe which have only five and four of the 10 sub-haplogroups, respectively. Within Thailand, diversity statistics for all four sub-regions follow the general pattern of Southern East Asia, but North Thailand stands out with its high diversity compared to the other regions. These results show that a small part of Southern East Asia harbors the full range of the mtDNA gene pool, and they emphasize the exceptional genetic status of Southern East Asia. This indicates that today's dogs can trace a major part of their ancestry to Southern East Asia or closely situated regions, highlighting Thailand as a region of special interest. Considering the large genetic diversity found in Thailand and that many neighboring regions, e.g., Myanmar and Laos, have not been studied for dog genetics, it is possible that large parts of the dog gene pool remain undiscovered. It will be an important task for future studies to fill in these blanks on the phylogeographic map.

Dingoes are wild canids living in Australia, originating from domestic dogs. They have lived isolated from both the wild and the domestic ancestor, making them a unique model for studying feralization. Here, we sequence the genomes of 10 dingoes and 2 New Guinea Singing Dogs. Phylogenetic and demographic analyses show that dingoes originate from dogs in southern East Asia, which migrated via Island Southeast Asia to reach Australia around 8300 years ago, and subsequently diverged into a genetically distinct population. Selection analysis identifies 50 positively selected genes enriched in digestion and metabolism, indicating a diet change during feralization of dingoes. Thirteen of these genes have shifted allele frequencies compared to dogs but not compared to wolves. Functional assays show that an A-to-G mutation in ARHGEF7 decreases the endogenous expression, suggesting behavioral adaptations related to the transitions in environment. Our results indicate that the feralization of the dingo induced positive selection on genomic regions correlated to neurodevelopment, metabolism and reproduction, in adaptation to a wild environment.

Dogs are the most phenotypically diverse mammalian species, and they possess more known heritable disorders than any other non-human mammal. Efforts to catalog and characterize genetic variation across well-chosen populations of canines are necessary to advance our understanding of their evolutionary history and genetic architecture. To date, no organized effort has been undertaken to sequence the world's canid populations. The Dog10K Consortium (http://www.dog10kgenomes.org) is an international collaboration of researchers from across the globe who will generate 20× whole genomes from 10 000 canids in 5 years. This effort will capture the genetic diversity that underlies the phenotypic and geographical variability of modern canids worldwide. Breeds, village dogs, niche populations and extended pedigrees are currently being sequenced, and de novo assemblies of multiple canids are being constructed. This unprecedented dataset will address the genetic underpinnings of domestication, breed formation, aging, behavior and morphological variation. More generally, this effort will advance our understanding of human and canine health.