Biology subjects

Ballard, J. W. O.

Publications and source records attributed to Ballard, J. W. O..

7 recordsLinked to original sources

bioRxiv2023

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

BackgroundOne 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. FindingsWe 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 nine previously published de novo canine assemblies show dingoes are monophyletic and basal to domestic dogs. Network analyses show that the mtDNA genome clusters within the southeastern lineage, as expected for an Alpine dingo. Comparison of regulatory regions identified two 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. Morphological data, comprising geometric morphometric assessment of cranial morphology place dingo Cooinda within population-level variation for Alpine dingoes. Magnetic resonance imaging of brain tissue show she had a larger cranial capacity than a similar-sized domestic dog. ConclusionsThese combined data support the hypothesis that the dingo Cooinda fits the spectrum of genetic and morphological 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.

genomics↗

bioRxiv2021

Acetyl-CoA metabolism drives epigenome change and contributes to carcinogenesis risk in fatty liver disease

The rate of nonalcoholic fatty liver disease (NAFLD)-associated hepatocellular carcinoma (HCC) is increasing worldwide, but the steps in precancerous hepatocytes which lead to HCC driver mutations are not well understood. Here we provide evidence that metabolically-driven histone hyperacetylation in steatotic hepatocytes can increase DNA damage to initiate carcinogenesis. Genome-wide histone acetylation is increased in steatotic livers of rodents fed high fructose or high fat diet. In vitro, steatosis relaxes chromatin and increases DNA damage marker {gamma}H2AX, which is reversed by inhibiting acetyl-CoA production. Steatosis-associated acetylation and {gamma}H2AX are enriched at gene clusters in telomere-proximal regions which contain HCC tumor suppressors in hepatocytes and human fatty livers. Regions of metabolically-driven epigenetic change also have increased levels of DNA mutation in non-cancerous tissue from NAFLD patients. Finally, genome-scale network modelling indicates that redox balance is a key contributor to this mechanism. Thus abnormal histone hyperacetylation is a potential initiating event in HCC carcinogenesis.

cancer biology↗

bioRxiv2020

Desert Dingo (Canis lupus dingo) genome provides insights into their role in the Australian ecosystem.

The dingo is Australias iconic top-order predator and arrived on the continent between 5,000-8,000 years ago. To provide an unbiased insight into its evolutionary affiliations and biological interactions, we coupled long-read DNA sequencing with a multiplatform scaffolding approach to produce an ab initio genome assembly of the desert dingo (85X coverage) we call CanLup_DDS. We compared this genome to the Boxer (CanFam3.1) and German Shepherd dog (CanFam_GSD) assemblies and characterized lineage-specific and shared genetic variation ranging from single- to megabase pair-sized variants. We identified 21,483 dingo-specific and 16,595 domestic dog-specific homozygous structural variants mediating genic and putative regulatory changes. Comparisons between the dingo and domestic dog builds detected unique inversions on Chromosome 16, structural variations in genes linked with starch metabolism, and seven differentially methylated genes. To experimentally assess genomic differences 17 dingoes and 15 German Shepherd dogs were fed parallel diets for 14 days. In dingoes, low AMY2B copy number and serum amylase levels are linked with high cholesterol and LDL levels. Gut microbiome analyses revealed enrichment of the family Clostridiaceae, which can utilize complex resistant starch, while scat metabolome studies identified high phenylethyl alcohol concentrations that we posit are linked with territory marking. Our study provides compelling genomic, microbiome, and metabolomic links showing the dingo has distinct physiology from domestic breed dogs with a unique role in the ecosystem.

genomics↗

bioRxiv2020

Chromosome-length genome assembly and structural variations of the primal Basenji dog (Canis lupus familiaris) genome

BackgroundBasenjis are considered an ancient dog breed of central African origins that still live and hunt with tribesmen in the African Congo. Nicknamed the barkless dog, Basenjis possess unique phylogeny, geographical origins and traits, making their genome structure of great interest. The increasing number of available canid reference genomes allows us to examine the impact the choice of reference genome makes with regard to reference genome quality and breed relatedness. ResultsHere, we report two high quality de novo Basenji genome assemblies: a female, China (CanFam_Bas), and a male, Wags. We conduct pairwise comparisons and report structural variations between assembled genomes of three dog breeds: Basenji (CanFam_Bas), Boxer (CanFam3.1) and German Shepherd Dog (GSD) (CanFam_GSD). CanFam_Bas is superior to CanFam3.1 in terms of genome contiguity and comparable overall to the high quality CanFam_GSD assembly. By aligning short read data from 58 representative dog breeds to three reference genomes, we demonstrate how the choice of reference genome significantly impacts both read mapping and variant detection. ConclusionsThe growing number of high-quality canid reference genomes means the choice of reference genome is an increasingly critical decision in subsequent canid variant analyses. The basal position of the Basenji makes it suitable for variant analysis for targeted applications of specific dog breeds. However, we believe more comprehensive analyses across the entire family of canids is more suited to a pangenome approach. Collectively this work highlights the importance the choice of reference genome makes in all variation studies.

genomics↗

bioRxiv2020

Metabolomics shows the Australian dingo has a unique plasma profile

Dingoes have not been artificially selected in the past 3,500 years. They occupy a wide range of the Australian mainland and play a crucial role as an apex predator with a generalist omnivorous feeding behaviour. In contrast, humans have selected breed dogs for novel and desirable traits. First, we explore whether the distinct evolutionary histories of dingoes and domestic dogs can lead to plasma metabolomic differences. We study metabolite composition differences between dingoes (n=15) and two domestic dog breeds (Basenji n= 9 and German Shepherd Dog: GSD n=10). After accounting for within group variation, 62 significant metabolite differences were detected between dingoes and domestic dogs, with a greater number of differences in protein (n= 14) and lipid metabolites (n= 12). Most differences were observed between dingoes and domestic dogs and fewest between the domestic dog breeds. Second, we investigate variation between pure dingoes (n=10) and dingo-dog hybrids (n=10) as hybridisation is common. We detected no significant differences in metabolite levels between dingoes and dingo-dog hybrids after Bonferroni correction. However, power analyses reported that increasing the sample size to 15 could result in differences in uridine 5-diphosphogalactose (UDPgal) levels related to galactose metabolism. We suggest this may be related to an increase in Amylase 2B copy number in hybrids. Our study illustrates that the dingo metabolome is significantly different from domestic dog breeds and hybridisation is likely to influence carbohydrate metabolism.

ecology↗

bioRxiv2020

Ancestral dietary change alters development of Drosophila larvae through MAPK signalling

Increasing evidence in animal species ranging from mammals to insects has revealed phenotypes that are caused by ancestral life experiences including stress and diet. The descendent phenotypes themselves are wide ranging, and include changes to behaviour, disease risk, metabolism, and growth. Ancestral dietary macronutrient composition, and quantity (over- and under-nutrition) have been shown to alter descendent growth, metabolism and behaviour. Several studies have identified inherited molecules in gametes which are altered by ancestral diet and are required for the transgenerational effect. However, there is less understanding of the developmental pathways in the period between fertilisation and adulthood that are altered by the inherited molecules. Here we identify a key role of the MAPK signalling pathway in mediating changes to Drosophila larval developmental timing due to variation in ancestral diet. We exposed grand-parental and great grand-parental generations to defined protein to carbohydrate (P:C) dietary ratios and measured developmental timing. Descendent developmental timing was consistently faster in the period between the embryonic and pupal stages when the ancestor had a higher P:C ratio diet. Transcriptional analysis of embryos, larvae and adults revealed extensive and long-lasting changes to the MAPK signalling pathway which controlled growth rate through regulation of ribosomal RNA transcription. The importance of these processes was supported by pharmacological inhibition of MAPK and rRNA proteins which reproduced the ancestral diet-induced developmental changes. This work provides insight into the role of developmental growth signalling networks in mediating non-genetic inheritance in the period between fertilisation and adult. Summary statementAncestral, diet-induced descendent developmental timing changes are caused by alteration of MAPK signalling pathways in the period between the embryo and pupal stages in Drosophila.

developmental biology↗

bioRxiv2018

Near-Infrared Spectroscopy for metabolite quantification and species identification

The aim of the study was to investigate the accuracy of near-infrared spectroscopy (NIRS) in determining triglyceride level and species of wild caught Drosophila. NIRS is a remote sensing method that uses the near-infrared region of the electromagnetic spectrum. It detects the absorption of light by molecular bonds and can be used with live insects. We employ the chemometric approach to combine spectra and reference data from a known sample to produce a multivariate calibration model. Once the calibration model was developed, we used an independent set to validate the accuracy of the calibration model. The optimized calibration model for triglyceride quantification yielded an accuracy of 73%. Simultaneously, we used NIRS to discriminate two species of Drosophila. Flies from independent sets were correctly classified into D. melanogaster and D. simulans with accuracy higher than 80%. Finally, we show that the biological interpretations derived from reference data and the NIRS predictions do not differ. These results suggest that NIRS has the potential to be used as a high throughput screening method to assess a live individual insects triglyceride level and taxonomic status.

biochemistry↗