Pervasive Effects of Aging on Gene Expression in Wild Wolves.
ABSTRACT: Gene expression levels change as an individual ages and responds to environmental conditions. With the exception of humans, such patterns have principally been studied under controlled conditions, overlooking the array of developmental and environmental influences that organisms encounter under conditions in which natural selection operates. We used high-throughput RNA sequencing (RNA-Seq) of whole blood to assess the relative impacts of social status, age, disease, and sex on gene expression levels in a natural population of gray wolves (Canis lupus). Our findings suggest that age is broadly associated with gene expression levels, whereas other examined factors have minimal effects on gene expression patterns. Further, our results reveal evolutionarily conserved signatures of senescence, such as immunosenescence and metabolic aging, between wolves and humans despite major differences in life history and environment. The effects of aging on gene expression levels in wolves exhibit conservation with humans, but the more rapid expression differences observed in aging wolves is evolutionarily appropriate given the species' high level of extrinsic mortality due to intraspecific aggression. Some expression changes that occur with age can facilitate physical age-related changes that may enhance fitness in older wolves. However, the expression of these ancestral patterns of aging in descendant modern dogs living in highly modified domestic environments may be maladaptive and cause disease. This work provides evolutionary insight into aging patterns observed in domestic dogs and demonstrates the applicability of studying natural populations to investigate the mechanisms of aging.
Project description:BACKGROUND:Whole genome re-sequencing data from dogs and wolves are now commonly used to study how natural and artificial selection have shaped the patterns of genetic diversity. Single nucleotide polymorphisms, microsatellites and variants in mitochondrial DNA have been interrogated for links to specific phenotypes or signals of domestication. However, copy number variation (CNV), despite its increasingly recognized importance as a contributor to phenotypic diversity, has not been extensively explored in canids. RESULTS:Here, we develop a new accurate probabilistic framework to create fine-scale genomic maps of segmental duplications (SDs), compare patterns of CNV across groups and investigate their role in the evolution of the domestic dog by using information from 34 canine genomes. Our analyses show that duplicated regions are enriched in genes and hence likely possess functional importance. We identify 86 loci with large CNV differences between dogs and wolves, enriched in genes responsible for sensory perception, immune response, metabolic processes, etc. In striking contrast to the observed loss of nucleotide diversity in domestic dogs following the population bottlenecks that occurred during domestication and breed creation, we find a similar proportion of CNV loci in dogs and wolves, suggesting that other dynamics are acting to particularly select for CNVs with potentially functional impacts. CONCLUSIONS:This work is the first comparison of genome wide CNV patterns in domestic and wild canids using whole-genome sequencing data and our findings contribute to study the impact of novel kinds of genetic changes on the evolution of the domestic dog.
Project description:BACKGROUND:Admixture can facilitate adaptation. For example, black wolves have obtained the variant causing black coat color through past hybridization with domestic dogs and have higher fitness than gray colored wolves. Another recent example of the transfer of adaptive variation between the two species has been suggested by the similarity between high altitude Tibetan mastiffs and wolves at the EPAS1 gene, a transcription factor induced in low oxygen environments. METHODS:Here, we investigate the directionality of admixture in EPAS1 between 28 reference highland gray wolves, 15 reference domestic dogs, and 21 putatively admixed highland wolves. This experimental design represents an expanded sample of Asian dogs and wolves from previous studies. Admixture was inferred using 17,709 publicly available SNP genotypes on canine chromosome 10. We additionally conducted a scan for positive selection in the highland dog genome. RESULTS:We find an excess of highland gray wolf ancestry at the EPAS1 locus in highland domestic dogs, suggesting adaptive introgression from wolves to dogs. The signal of admixture is limited in genomic extent to a small region on chromosome 10, indicating that it is the focus of selection in an oxygen-limited environment. DISCUSSION:Our results suggest that an adaptive variant of EPAS1 in highland wolves was transferred to highland dogs, carrying linked variants that potentially function in hypoxia response at high elevation. The intertwined history of dogs and wolves ensures a unique evolutionary dynamic where variants that have appeared in the history of either species can be tested for their effects on fitness under natural and artificial selection. Such coupled evolutionary histories may be key to the persistence of wild canines and their domesticated kin given the increasing anthropogenic modifications that characterize the future of both species.
Project description:Dogs were the first domestic animal, but little is known about their population history and to what extent it was linked to humans. We sequenced 27 ancient dog genomes and found that all dogs share a common ancestry distinct from present-day wolves, with limited gene flow from wolves since domestication but substantial dog-to-wolf gene flow. By 11,000 years ago, at least five major ancestry lineages had diversified, demonstrating a deep genetic history of dogs during the Paleolithic. Coanalysis with human genomes reveals aspects of dog population history that mirror humans, including Levant-related ancestry in Africa and early agricultural Europe. Other aspects differ, including the impacts of steppe pastoralist expansions in West and East Eurasia and a near-complete turnover of Neolithic European dog ancestry.
Project description:The overall similarity of the skull shape of some dog breeds with that of juvenile wolves begs the question if and how ontogenetic changes such as paedomorphosis (evolutionary juvenilisation) played a role in domestication. Here we test for changes in patterns of development and growth during dog domestication. We present the first geometric morphometric study using ontogenetic series of dog and wolf crania, and samples of dogs with relatively ancestral morphology and from different time periods. We show that patterns of juvenile-to-adult morphological change are largely similar in wolves and domestic dogs, but differ in two ways. First, dog skulls show unique (neomorphic) features already shortly after birth, and these features persist throughout postnatal ontogeny. Second, at any given age, juvenile dogs exhibit skull shapes that resemble those of consistently younger wolves, even in dog breeds that do not exhibit a 'juvenilized' morphology as adults. These patterns exemplify the complex nature of evolutionary changes during dog domestication: the cranial morphology of adult dogs cannot simply be explained as either neomorphic or paedomorphic. The key to our understanding of dog domestication may lie in a closer comparative examination of developmental phases.
Project description:Wolves (Canis lupus) and their domesticated and close relatives, dogs (Canis lupus familiaris), have great differences in their diets and living environments. To the best of our knowledge, the fundamental question of how the abundance and function of the gut microbiota of domestic dogs evolved to adapt to the changes in host feeding habits has yet to be addressed. In this study, our comparative analyses of gut metagenomes showed that the abundance of gut microbiota between the two species have some significant differences. Furthermore, a number of taxa observed in higher numbers in domestic dogs are related to carbohydrate metabolism, which may be because that there were more complicated polysaccharides in dogs diets than that in wolves diets. A significant difference in the abundance of genes encoding glycosyltransferase family 34 (GT34), carbohydrate-binding module family 25 (CBM25), and glycoside hydrolase family 13 (GH13) between the gut microbiota metagenomes of domestic dogs and gray wolves also supported this observation. Furthermore, the domestic dog gut microbiota has greater valine, leucine and isoleucine biosynthesis and nitrogen metabolism. This result showed that compared with wolves, the domestic dog diet contains a smaller amount of animal protein, which is consistent with the dietary composition of wolves and dogs. Our results indicate that the function and abundance of gut microbiota of domestic dogs has been adapted to domestication, which is of great significance for the ability of domestic dogs to adapt to changes in food composition.
Project description:The evolutionary importance of hybridization as a source of new adaptive genetic variation is rapidly gaining recognition. Hybridization between coyotes and wolves may have introduced adaptive alleles into the coyote gene pool that facilitated an expansion in their geographic range and dietary niche. Furthermore, hybridization between coyotes and domestic dogs may facilitate adaptation to human-dominated environments. We genotyped 63 ancestry-informative single-nucleotide polymorphisms in 427 canids to examine the prevalence, spatial distribution and the ecology of admixture in eastern coyotes. Using multivariate methods and Bayesian clustering analyses, we estimated the relative contributions of western coyotes, western and eastern wolves, and domestic dogs to the admixed ancestry of Ohio and eastern coyotes. We found that eastern coyotes form an extensive hybrid swarm, with all our samples having varying levels of admixture. Ohio coyotes, previously thought to be free of admixture, are also highly admixed with wolves and dogs. Coyotes in areas of high deer density are genetically more wolf-like, suggesting that natural selection for wolf-like traits may result in local adaptation at a fine geographic scale. Our results, in light of other previously published studies of admixture in Canis, revealed a pattern of sex-biased hybridization, presumably generated by male wolves and dogs mating with female coyotes. This study is the most comprehensive genetic survey of admixture in eastern coyotes and demonstrates that the frequency and scope of hybridization can be quantified with relatively few ancestry-informative markers.
Project description:The evolutionary relationships between extinct and extant lineages provide important insight into species' response to environmental change. The grey wolf is among the few Holarctic large carnivores that survived the Late Pleistocene megafaunal extinctions, responding to that period's profound environmental changes with loss of distinct lineages and phylogeographic shifts, and undergoing domestication. We reconstructed global genome-wide phylogeographic patterns in modern wolves, including previously underrepresented Siberian wolves, and assessed their evolutionary relationships with a previously genotyped wolf from Taimyr, Siberia, dated at 35 Kya. The inferred phylogeographic structure was affected by admixture with dogs, coyotes and golden jackals, stressing the importance of accounting for this process in phylogeographic studies. The Taimyr lineage was distinct from modern Siberian wolves and constituted a sister lineage of modern Eurasian wolves and domestic dogs, with an ambiguous position relative to North American wolves. We detected gene flow from the Taimyr lineage to Arctic dog breeds, but population clustering methods indicated closer similarity of the Taimyr wolf to modern wolves than dogs, implying complex post-divergence relationships among these lineages. Our study shows that introgression from ecologically diverse con-specific and con-generic populations was common in wolves' evolutionary history, and could have facilitated their adaptation to environmental change.
Project description:Domestic dogs have been recognized for their social sensitivity and aptitude in human-guided tasks. For example, prior studies have demonstrated that dogs look to humans when confronted with an unsolvable task; an action often interpreted as soliciting necessary help. Conversely, wolves persist on such tasks. While dogs' 'looking back' behaviour has been used as an example of socio-cognitive advancement, an alternative explanation is that pet dogs show less persistence on independent tasks more generally. In this study, pet dogs, shelter dogs and wolves were given up to three opportunities to open a solvable puzzle box: when subjects were with a neutral human caretaker, alone and when encouraged by the human. Wolves were more persistent and more successful on this task than dogs, with 80% average success rate for wolves versus a 5% average success rate for dogs in both the human-in and alone conditions. Dogs showed increased contact with the puzzle box during the encouragement condition, but only a moderate increase in problem-solving success. Social sensitivity appears to play an important role in pet and shelter dogs' willingness to engage in problem-solving behaviour, which could suggest generalized dependence on, or deference to, human action.
Project description:Population bottlenecks, inbreeding, and artificial selection can all, in principle, influence levels of deleterious genetic variation. However, the relative importance of each of these effects on genome-wide patterns of deleterious variation remains controversial. Domestic and wild canids offer a powerful system to address the role of these factors in influencing deleterious variation because their history is dominated by known bottlenecks and intense artificial selection. Here, we assess genome-wide patterns of deleterious variation in 90 whole-genome sequences from breed dogs, village dogs, and gray wolves. We find that the ratio of amino acid changing heterozygosity to silent heterozygosity is higher in dogs than in wolves and, on average, dogs have 2-3% higher genetic load than gray wolves. Multiple lines of evidence indicate this pattern is driven by less efficient natural selection due to bottlenecks associated with domestication and breed formation, rather than recent inbreeding. Further, we find regions of the genome implicated in selective sweeps are enriched for amino acid changing variants and Mendelian disease genes. To our knowledge, these results provide the first quantitative estimates of the increased burden of deleterious variants directly associated with domestication and have important implications for selective breeding programs and the conservation of rare and endangered species. Specifically, they highlight the costs associated with selective breeding and question the practice favoring the breeding of individuals that best fit breed standards. Our results also suggest that maintaining a large population size, rather than just avoiding inbreeding, is a critical factor for preventing the accumulation of deleterious variants.
Project description:Although considerable progress has been made in understanding the genetic basis of morphologic traits (for example, body size and coat color) in dogs and wolves, the genetic basis of their behavioral divergence is poorly understood. An integrative approach using both behavioral and genetic data is required to understand the molecular underpinnings of the various behavioral characteristics associated with domestication. We analyze a 5-Mb genomic region on chromosome 6 previously found to be under positive selection in domestic dog breeds. Deletion of this region in humans is linked to Williams-Beuren syndrome (WBS), a multisystem congenital disorder characterized by hypersocial behavior. We associate quantitative data on behavioral phenotypes symptomatic of WBS in humans with structural changes in the WBS locus in dogs. We find that hypersociability, a central feature of WBS, is also a core element of domestication that distinguishes dogs from wolves. We provide evidence that structural variants in GTF2I and GTF2IRD1, genes previously implicated in the behavioral phenotype of patients with WBS and contained within the WBS locus, contribute to extreme sociability in dogs. This finding suggests that there are commonalities in the genetic architecture of WBS and canine tameness and that directional selection may have targeted a unique set of linked behavioral genes of large phenotypic effect, allowing for rapid behavioral divergence of dogs and wolves, facilitating coexistence with humans.