Genetic studies of rare and endangered species often focus on defining and preserving genetically distinct populations, especially those having unique adaptations 1, 2. Much less attention is ...directed at understanding the landscape of deleterious variation, an insidious consequence of geographic isolation and the inefficiency of natural selection to eliminate harmful variants in small populations 3–5. With population sizes of many vertebrates decreasing and isolation increasing through habitat fragmentation and loss, understanding the extent and nature of deleterious variation in small populations is essential for predicting and enhancing population persistence. The Channel Island fox (Urocyon littoralis) is a dwarfed species that inhabits six of California’s Channel Islands and is derived from the mainland gray fox (U. cinereoargenteus). These isolated island populations have persisted for thousands of years at extremely small population sizes 6, 7 and, consequently, are a model for testing ideas about the accumulation of deleterious variation in small populations under natural conditions. Analysis of complete genome sequence data from island foxes shows a dramatic decrease in genome-wide variation and a sharp increase in the homozygosity of deleterious variants. The San Nicolas Island population has a near absence of variation, demonstrating a unique genetic flatlining that is punctuated by heterozygosity hotspots, enriched for olfactory receptor genes and other genes with high levels of ancestral variation. These findings question the generality of the small-population paradigm that maintains substantial genetic variation is necessary for short- and long-term persistence.
•Genomic monomorphism on a scale not seen previously in eukaryotes is shown•Deleterious variation and loss-of-function mutations are not purged•Drift, without balancing selection, accounts for peaks of heterozygosity•Persistence despite the absence of variation questions its role in small populations
Robinson et al. show that the island fox has drastically reduced genetic variation and high levels of deleterious mutations, suggesting that selection has not purged harmful variants. Remarkably, the San Nicolas Island fox has a near absence of variation, questioning the importance of genetic variation in the long-term persistence of small populations.
In multiple studies DNA methylation has proven to be an accurate biomarker of age. To develop these biomarkers, the methylation of multiple CpG sites is typically linearly combined to predict ...chronological age. By contrast, in this study we apply the Universal PaceMaker (UPM) model to investigate changes in DNA methylation during aging. The UPM was initially developed to study rate acceleration/deceleration in sequence evolution. Rather than identifying which linear combinations of sites predicts age, the UPM models the rates of change of multiple CpG sites, as well as their starting methylation levels, and estimates the age of each individual to optimize the model fit. We refer to the estimated age as the "epigenetic age", which is in contrast to the known chronological age of each individual. We construct a statistical framework and devise an algorithm to determine whether a genomic pacemaker is in effect (i.e rates of change vary with age). The decision is made by comparing two competing likelihood based models, the molecular clock (MC) and UPM. For the molecular clock model, we use the known chronological age of each individual and fit the methylation rates at multiple sites, and express the problem as a linear least squares and solve it in polynomial time. For the UPM case, the search space is larger as we are fitting both the epigenetic age of each individual as well as the rates for each site, yet we succeed to reduce the problem to the space of individuals and polynomial in the more significant space-the methylated sites. We first tested our algorithm on simulated data to elucidate the factors affecting the identification of the pacemaker model. We find that, provided with enough data, our algorithm is capable of identifying a pacemaker even when a weak signal is present in the data. Based on these results, we applied our method to DNA methylation data from human blood from individuals of various ages. Although the improvement in variance across sites between the UPM and MC was small, the results suggest that the existence of a pacemaker is highly significant. The PaceMaker results also suggest a decay in the rate of change in DNA methylation with age.
Variation across dog breeds presents a unique opportunity to investigate the evolution and biological basis of complex behavioural traits. We integrated behavioural data from more than 14 000 dogs ...from 101 breeds with breed-averaged genotypic data (
= 5697 dogs) from over 100 000 loci in the dog genome. We found high levels of among-breed heritability for 14 behavioural traits (the proportion of trait variance attributable to genetic similarity among breeds). We next identified 131 single nucleotide polymorphisms associated with breed differences in behaviour, which were found in genes that are highly expressed in the brain and enriched for neurobiological functions and developmental processes, suggesting that they may be functionally associated with behavioural differences. Our results shed light on the heritability and genetic architecture of complex behavioural traits and identify dogs as a powerful model in which to address these questions.
Domestic dogs exhibit tremendous phenotypic diversity, including a greater variation in body size than any other terrestrial mammal. Here, we generate a high density map of canine genetic variation ...by genotyping 915 dogs from 80 domestic dog breeds, 83 wild canids, and 10 outbred African shelter dogs across 60,968 single-nucleotide polymorphisms (SNPs). Coupling this genomic resource with external measurements from breed standards and individuals as well as skeletal measurements from museum specimens, we identify 51 regions of the dog genome associated with phenotypic variation among breeds in 57 traits. The complex traits include average breed body size and external body dimensions and cranial, dental, and long bone shape and size with and without allometric scaling. In contrast to the results from association mapping of quantitative traits in humans and domesticated plants, we find that across dog breeds, a small number of quantitative trait loci (< or = 3) explain the majority of phenotypic variation for most of the traits we studied. In addition, many genomic regions show signatures of recent selection, with most of the highly differentiated regions being associated with breed-defining traits such as body size, coat characteristics, and ear floppiness. Our results demonstrate the efficacy of mapping multiple traits in the domestic dog using a database of genotyped individuals and highlight the important role human-directed selection has played in altering the genetic architecture of key traits in this important species.
This bibliography provides a collection of references that documents the evolution of studies evidencing interbreeding among Canis species in North America. Over the past several decades, advances in ...biology and genomic technology greatly improved our ability to detect and characterize species interbreeding, which has significance for understanding species in a changing landscape as well as for endangered species management. This bibliography includes a discussion within each category of interbreeding, the timeline of developing evidence, and includes a review of past research conducted on experimental crosses. Research conducted in the early 20th century is rich with detailed records and photographs of hybrid offspring development and behavior. With the progression of molecular methods, studies can estimate historical demographic parameters and detect chromosomal patterns of ancestry. As these methods continue to increase in accessibility, the field will gain a deeper and richer understanding of the evolutionary history of North American Canis.
Hybrid zones typically contain novel gene combinations that can be tested by natural selection in a unique genetic context. Parental haplotypes that increase fitness can introgress beyond the hybrid ...zone, into the range of parental species. We used the Affymetrix canine SNP genotyping array to identify genomic regions tagged by multiple ancestry informative markers that are more frequent in an admixed population than expected. We surveyed a hybrid zone formed in the last 100 years as coyotes expanded their range into eastern North America. Concomitant with expansion, coyotes hybridized with wolves and some populations became more wolflike, such that coyotes in the northeast have the largest body size of any coyote population. Using a set of 3102 ancestry informative markers, we identified 60 differentially introgressed regions in 44 canines across this admixture zone. These regions are characterized by an excess of exogenous ancestry and, in northeastern coyotes, are enriched for genes affecting body size and skeletal proportions. Further, introgressed wolf‐derived alleles have penetrated into Southern US coyote populations. Because no wolves currently exist in this area, these alleles are unlikely to have originated from recent hybridization. Instead, they probably originated from intraspecific gene flow or ancient admixture. We show that grey wolf and coyote admixture has far‐reaching effects and, in addition to phenotypically transforming admixed populations, allows for the differential movement of alleles from different parental species to be tested in new genomic backgrounds.
Sarcoptic mange is a highly contagious skin disease caused by the ectoparasitic mite Sarcoptes scabiei. Although it afflicts over 100 mammal species worldwide, sarcoptic mange remains a disease ...obscured by variability at the individual, population and species levels. Amid this variability, it is critical to identify consistent drivers of morbidity, particularly at the skin barrier.
Using culture-independent next generation sequencing, we characterized the skin microbiome of three species of North American canids: coyotes (Canis latrans), red foxes (Vulpes vulpes) and gray foxes (Urocyon cinereoargenteus). We compared alpha and beta diversity between mange-infected and uninfected canids using the Kruskal-Wallis test and multivariate analysis of variance with permutation. We used analysis of composition of microbes and gneiss balances to perform differential abundance testing between infection groups.
We found remarkably consistent signatures of microbial dysbiosis associated with mange infection. Across genera, mange-infected canids exhibited reduced microbial diversity, altered community composition and increased abundance of opportunistic pathogens. The primary bacteria comprising secondary infections were Staphylococcus pseudintermedius, previously associated with canid ear and skin infections, and Corynebacterium spp., previously found among the gut flora of S. scabiei mites and hematophagous arthropods.
This evidence suggests that sarcoptic mange infection consistently alters the canid skin microbiome and facilitates secondary bacterial infection, as seen in humans and other mammals infected with S. scabiei mites. These results provide valuable insights into the pathogenesis of mange at the skin barrier of North American canids and can inspire novel treatment strategies. By adopting a "One Health" framework that considers mites, microbes and the potential for interspecies transmission, we can better elucidate the patterns and processes underlying this ubiquitous and enigmatic disease.
High-throughput genotyping technologies developed for model species can potentially increase the resolution of demographic history and ancestry in wild relatives. We use a SNP genotyping microarray ...developed for the domestic dog to assay variation in over 48K loci in wolf-like species worldwide. Despite the high mobility of these large carnivores, we find distinct hierarchical population units within gray wolves and coyotes that correspond with geographic and ecologic differences among populations. Further, we test controversial theories about the ancestry of the Great Lakes wolf and red wolf using an analysis of haplotype blocks across all 38 canid autosomes. We find that these enigmatic canids are highly admixed varieties derived from gray wolves and coyotes, respectively. This divergent genomic history suggests that they do not have a shared recent ancestry as proposed by previous researchers. Interspecific hybridization, as well as the process of evolutionary divergence, may be responsible for the observed phenotypic distinction of both forms. Such admixture complicates decisions regarding endangered species restoration and protection.
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