The Australian dingo is an early offshoot of modern breed dogs.

Dogs are uniquely associated with human dispersal and bring transformational insight into the domestication process. Dingoes represent an intriguing case within canine evolution being geographically isolated for thousands of years. Here, we present a high-quality de novo assembly of a pure dingo (CanFam_DDS). We identified large chromosomal differences relative to the current dog reference (CanFam3.1) and confirmed no expanded pancreatic amylase gene as found in breed dogs. Phylogenetic analyses using variant pairwise matrices show that the dingo is distinct from five breed dogs with 100% bootstrap support when using Greenland wolf as the outgroup. Functionally, we observe differences in methylation patterns between the dingo and German shepherd dog genomes and differences in serum biochemistry and microbiome makeup. Our results suggest that distinct demographic and environmental conditions have shaped the dingo genome. In contrast, artificial human selection has likely shaped the genomes of domestic breed dogs after divergence from the dingo

The Australian dingo is an early offshoot of modern breed dogs

Dogs are uniquely associated with human dispersal and bring transformational insight into the domestication process. Dingoes represent an intriguing case within canine evolution being geographically isolated for thousands of years. Here, we present a high-quality de novo assembly of a pure dingo (CanFam_DDS). We identified large chromosomal differences relative to the current dog reference (CanFam3.1) and confirmed no expanded pancreatic amylase gene as found in breed dogs. Phylogenetic analyses using variant pairwise matrices show that the dingo is distinct from five breed dogs with 100% bootstrap support when using Greenland wolf as the outgroup. Functionally, we observe differences in methylation patterns between the dingo and German shepherd dog genomes and differences in serum biochemistry and microbiome makeup. Our results suggest that distinct demographic and environmental conditions have shaped the dingo genome. In contrast, artificial human selection has likely shaped the genomes of domestic breed dogs after divergence from the dingo

The Australasian dingo archetype: de novo chromosome-length genome assembly, DNA methylome, and cranial morphology

BACKGROUND: One difficulty in testing the hypothesis that the Australasian dingo is a functional intermediate between wild wolves and domesticated breed dogs is that there is no reference specimen. Here we link a high-quality de novo long-read chromosomal assembly with epigenetic footprints and morphology to describe the Alpine dingo female named Cooinda. It was critical to establish an Alpine dingo reference because this ecotype occurs throughout coastal eastern Australia where the first drawings and descriptions were completed. FINDINGS: We generated a high-quality chromosome-level reference genome assembly (Canfam_ADS) using a combination of Pacific Bioscience, Oxford Nanopore, 10X Genomics, Bionano, and Hi-C technologies. Compared to the previously published Desert dingo assembly, there are large structural rearrangements on chromosomes 11, 16, 25, and 26. Phylogenetic analyses of chromosomal data from Cooinda the Alpine dingo and 9 previously published de novo canine assemblies show dingoes are monophyletic and basal to domestic dogs. Network analyses show that the mitochondrial DNA genome clusters within the southeastern lineage, as expected for an Alpine dingo. Comparison of regulatory regions identified 2 differentially methylated regions within glucagon receptor GCGR and histone deacetylase HDAC4 genes that are unmethylated in the Alpine dingo genome but hypermethylated in the Desert dingo. Morphologic data, comprising geometric morphometric assessment of cranial morphology, place dingo Cooinda within population-level variation for Alpine dingoes. Magnetic resonance imaging of brain tissue shows she had a larger cranial capacity than a similar-sized domestic dog. CONCLUSIONS: These combined data support the hypothesis that the dingo Cooinda fits the spectrum of genetic and morphologic characteristics typical of the Alpine ecotype. We propose that she be considered the archetype specimen for future research investigating the evolutionary history, morphology, physiology, and ecology of dingoes. The female has been taxidermically prepared and is now at the Australian Museum, Sydney

Toxicology and ecotoxicology of para-aminopropiophenone (PAPP) – a new predator control tool for stoats and feral cats in New Zealand

Para-aminopropiophenone (PAPP) paste was approved as a stoat control agent in New Zealand by the Environmental Protection Authority in August 2011 and for feral cat control in November 2011. PAPP was originally researched in Europe and the USA as treatment for cyanide and radiation poisoning. Over the last 10 years, our research has focused on several factors, including determining its toxicity to predators, field effectiveness for controlling stoats and feral cats, animal welfare profile, toxicology, ecotoxicology, and understanding and reducing non-target risks. PAPP has been developed specifically for the control of stoats and feral cats because of the special sensitivity displayed by these species. Its toxicity is mediated by the induction of methaemoglobinaemia (the ferric state of haemoglobin). Normally, methaemoglobin levels in the blood are below 1%. Levels of methaemoglobin in the blood above 70% are usually fatal, creating a lethal deficit of oxygen in cardiac muscle and the brain. In stoats and feral cats, death after a lethal dose usually occurs within 2 h after eating bait, with clinical signs first appearing in 10 to 20 min for stoats and at around 35 min for cats. Animals become lethargic and sleepy before they die, hence PAPP is relatively humane. A simple antidote exists, namely methylene blue. Further, birds display a lack of toxicity to PAPP when compared with other vertebrate pesticides. A paste containing 40% PAPP has been developed for use in meat baits in New Zealand. A toxic dose for stoats and feral cats is achieved when pea-sized amounts of paste are delivered in 10–20 g meat baits. When meat baits containing PAPP are applied in bait stations in field settings, stoat and feral cat numbers can be rapidly reduced. However, there has been limited practical experience with PAPP to date, especially when compared with alternative tools such as traps or sodium monofluoroacetate (1080) baits. Additional practical experience should enable the effective use of PAPP as a tool to help protect native species from introduced predators. In the future, PAPP will be developed in long-life bait and in a resetting toxin delivery system

Spontaneous Goiter and Cancer of the Thyroid in Animals

Author Institution: Department of Pathology, College of Medicine, The Ohio State University, Columbus 1

Diversifying selection between pure-breed and free-breeding dogs inferred from genome-wide SNP analysis

Domesticated species are often composed of distinct populations differing in the character and strength of artificial and natural selection pressures, providing a valuable model to study adaptation. In contrast to pure-breed dogs that constitute artificially maintained inbred lines, free-ranging dogs are typically free-breeding, i.e. unrestrained in mate choice. Many traits in free-breeding dogs (FBDs) may be under similar natural and sexual selection conditions to wild canids, while relaxation of sexual selection is expected in pure-breed dogs. We used a Bayesian approach with strict false-positive control criteria to identify FST-outlier SNPs between FBDs and either European or East Asian breeds, based on 167,989 autosomal SNPs. By identifying outlier SNPs located within coding genes, we found four candidate genes under diversifying selection shared by these two comparisons. Three of them are associated with the Hedgehog (HH) signalling pathway regulating vertebrate morphogenesis. A comparison between FBDs and East Asian breeds also revealed diversifying selection on BBS6 gene, which was earlier shown to cause snout shortening and dental crowding via disrupted HH signalling. Our results suggest that relaxation of natural and sexual selection in pure-breed dogs as opposed to FBDs could have led to mild changes in regulation of the HH signalling pathway. HH inhibits adhesion and migration of neural crest cells from neural tube, and minor deficits of these cells during embryonic development have been proposed as the underlying cause of “domestication syndrome”. This suggests that the process of breed formation involved the same genetic and developmental pathways as the process of domestication

Determining the antiquity of dog origins: canine domestication as a model for the consilience between molecular genetics and archaeology

Archaeologists have favored a date of 14,000-15,000 years before present (BP) for canine domestication. However, recent studies of mutations in the mitochondrial DNA sequence by molecular geneticists have implied that dogs were domesticated over 100,000 years ago, which has challenged traditional theory. Geneticists have further hypothesized that dogs originated from wolf ancestors based upon the number of substitutions observed in dog and wolf haplotypes. Although both disciplines provide substantial evidence for their theories, the origin of dog domestication remains controversial. Several areas continue to be debatable. First, both geneticists and archaeologists incorrectly use the term domestication to describe events that clearly can not be proven to under human control. Second, the evolutionary development of canines is viewed by molecular biologists as well as archaeologist to be indicators of domestication without any further exploration of other probable causes. Third, the studies in canine genetics are so complex that most archaeologists have difficulty in providing evidence that would be contradictory to molecular theory. Fourth, both fields of study continually ignore innate behavioral characteristics of wolves that would make domestication highly improbable. Fifth, geneticists rely heavily on data gathered from sequencing of mitochondrial DNA, which has been assumed to maternally inherited. However recent human studies have shown that this assumption has now been proven to be incorrect. And finally, not only are morphological traits of fossilized dogs and wolves so similar that making a taxonomic identification improbable, but also the amount of archaeological remains available are too sparse and fragmented for accurate affiliation. An alternate theory of canine domestication will be proposed utilizing data gathered from the archaeological record and molecular research. I hypothesize that dogs diverged naturally from wolves 100,000 years ago as a result of the natural course of evolution, not human intervention, and had already evolved into a dog prior to being domesticated by humans 14,000-15,000 years ago. Evidence will be presented to clearly show that this hypothesis is a more accurate scenario of canine domestication

Natural and human-driven selection of a single non-coding body size variant in ancient and modern canids

Domestic dogs (Canis lupus familiaris) are the most variable-sized mammalian species on Earth, displaying a 40-fold size difference between breeds.1 Although dogs of variable size are found in the archeological record,2, 3, 4 the most dramatic shifts in body size are the result of selection over the last two centuries, as dog breeders selected and propagated phenotypic extremes within closed breeding populations.5 Analyses of over 200 domestic breeds have identified approximately 20 body size genes regulating insulin processing, fatty acid metabolism, TGFβ signaling, and skeletal formation.6, 7, 8, 9, 10 Of these, insulin-like growth factor 1 (IGF1) predominates, controlling approximately 15% of body size variation between breeds.8 The identification of a functional mutation associated with IGF1 has thus far proven elusive.6,10,11 Here, to identify and elucidate the role of an ancestral IGF1 allele in the propagation of modern canids, we analyzed 1,431 genome sequences from 13 species, including both ancient and modern canids, thus allowing us to define the evolutionary history of both ancestral and derived alleles at this locus. We identified a single variant in an antisense long non-coding RNA (IGF1-AS) that interacts with the IGF1 gene, creating a duplex. While the derived mutation predominates in both modern gray wolves and large domestic breeds, the ancestral allele, which predisposes to small size, was common in small-sized breeds and smaller wild canids. Our analyses demonstrate that this major regulator of canid body size nearly vanished in Pleistocene wolves, before its recent resurgence resulting from human-imposed selection for small-sized breed dogs

Hundi (Canis lupus) populatsioonid Eestis ja Euroopas: geneetiline mitmekesisus, populatsiooni struktuur ja -protsessid ning hübridiseerimine koertega

Väitekirja elektrooniline versioon ei sisalda publikatsioone.Ajal, mil mitmete hundipopulatsioonide levila on Euroopas suurenemas, on teadmised hundi populatsioonigeneetikast vajalikud liigi jaoks oluliste kaitse- ja majandamisotsuste tegemiseks ja seda nii kohalike populatsioonide kui ka üleeuroopalisel tasandil. Käesoleva töö peamisteks eesmärkideks oli uurida Eesti ja Läti hundipopulatsioonide struktuuri ja –protsesse, hübridiseerumist koertega ning laiemalt kogu Euroopa huntide ruumilis-geneetilise mitmekesisuse mustreid ja trende. Kasutades nii emaliini, isaliini kui ka biparentaalseid geneetilisi markereid kombineerivat analüüsi, tuvastasime Eestis (esmakordselt) ja Lätis hundi ja koera hübriidid, sealjuures kaks hübriidi Lätist esindasid väga haruldast, Euroopas esmakordselt tuvastatud hübridiseerimisjuhtumit - emase koera ja isase hundi vahel. Eestit ja Lätit hõlmav hundipopulatsiooni geneetilisel analüüsil leiti neli geneetiliselt eristuvat rühma ning uudne DResD analüüs tuvastas populatsioonis migratsioonikoridori ning liikumisbarjääre ja kontakttsoone eri geneetiliste rühmade vahel. Suuremat osa Euroopa hundipopulatsioonidest hõlmav meta-analüüs tuvastas olulise ruumilise mitmekesisuse trendi – huntide madalaim geneetiline mitmekesisus esines Euroopa edelaosas ja kõrgeim kirdeosas. Tulemustes selgunud ruumilise autokorrelatsiooni vahemik 650-850 km näitab, et konkreetse hundipopulatsiooni geneetilist mitmekesisust võivad mõjutada hundipopulatsioonid, mis asuvad kuni 850 km kaugusel. Enamik Euroopa hundipopulatsioonidest on silmitsi sarnaste, inimese poolt otseselt või kaudselt seotud ohtudega: küttimine (sealhulgas salaküttimine), inimeste madal sallivus hundi suhtes, konfliktid kariloomade murdmise tõttu, elupaikade hävimine ning võimalik hübridiseerumine koertega. Selleks, et hunt säiliks Euroopas pikka aega ja soodsas seisundis, on vaja suurendada Euroopa hundipopulatsioonide üldist arvukust ja soodustada loomade levikut ja populatsioonide-siseseid ja -vahelisi seoseid. Hundi teaduspõhiseks kaitsmiseks ja majandamiseks nii piirkondlikel kui ka üleeuroopalisel skaalal, on hundipopulatsioone vaja hallata kui bioloogilisi üksusi, mis nõuab kõiki Euroopa hundipopulatsioone hõlmavaid täiendavaid geneetilisi analüüse, et teha kindlaks populatsioonide täpne arv, ruumiline jaotus, geenisiirde ulatused ning hübridiseerumise sageduse koertega.As many wolf populations in Europe are expanding their range, knowledge of population genetics are of great importance for effective conservation and management of the species at both local and over-European scales. The main goal of this thesis was to provide information on wolf population structure and processes in Europe with a particular emphasis on Estonia and Latvia, including the wolf-dog hybridization. Using a combined analysis of maternal, paternal and biparental genetic markers, hybridization between grey wolf and domestic dog was ascertained in Estonia (for the first time) and in Latvia. The two hybrids from Latvia represented a very rare case of hybridization – the first record from Europe – between a female dog and a male wolf. Population structure analysis demonstrated that wolf popu¬lation shared between Estonia and Latvia is represented by four genetic groups. The spatially explicit DResD analysis provided clear evidence of spatial variation of genetic divergence, revealing a migration corridor, barriers, and several contact zones between different genetic groups. In a meta-analysis covering most of the European wolf populations, significant spatial trend in heterozygosity across Europe from south-west (lowest genetic diversity) to north-east (highest) was found. The range of spatial autocorrelation of 650−850 km suggests, that the genetic diversity of a given wolf population can be influenced by populations up to 850 km away. Various human-related factors are undoubtedly the main source of threats to wolf populations in Europe: the majority of populations face similar common threats such as overharvesting (including poaching), low public acceptance, conflicts due to livestock depredation, habitat destruction, barriers to gene flow and interactions with dogs leading to possible hybridization. For the long-term survival and favourable conservation status of European wolves there is a need to increase the overall population size and favour wolf dispersal and connectivity among and within populations. For science-based wolf conservation and manage¬ment at regional and Europe-wide scales it was suggested to manage wolf populations according to biological units, which requires additional genetic analysis covering all wolf populations in Europe to define the exact number and spatial distribution of populations