Project description:The identity of most functional elements in the mammalian genome and the phenotypes they impact are unclear. Here, we perform a genome-wide comparative analysis of patterns of accelerated evolution in species with highly distinctive traits to discover candidate functional elements for clinically important phenotypes. We identify accelerated regions (ARs) in the elephant, hibernating bat, orca, dolphin, naked mole rat and thirteen-lined ground squirrel lineages in mammalian conserved regions, uncovering ~33,000 elements that bind hundreds of different regulatory proteins in humans and mice. ARs in the elephant, the largest land mammal, are uniquely enriched at elephant DNA damage response genes and changed conserved regulatory sites. The genomic hotspot for elephant ARs is the E3 ligase subunit of the Fanconi Anemia Complex, a master regulator of DNA repair. Additionally, ARs in the six species are associated with specific human clinical phenotypes that have apparent concordance with overt traits in each species.
Project description:Background Methylation of CG dinucleotides constitutes a critical system of epigenetic memory in bony vertebrates, where it modulates gene expression and suppresses transposon activity. The genomes of studied vertebrates are pervasively hypermethylated, with the exception of regulatory elements such as transcription start sites (TSSs), where the presence of methylation is associated with gene silencing. This system is not found in the sparsely methylated genomes of invertebrates, and establishing how it arose during early vertebrate evolution is impeded by a paucity of epigenetic data from basal vertebrates. Methods We perform whole-genome bisulfite sequencing to generate the first genome-wide methylation profiles of a cartilaginous fish, the elephant shark Callorhinchus milii. Employing these to determine the elephant shark methylome structure and its relationship with expression, we compare this with higher vertebrates and an invertebrate chordate using published methylation and transcriptome data. Results Like higher vertebrates, the majority of elephant shark CG sites are highly methylated, and methylation is abundant across the genome rather than patterned in the mosaic configuration of invertebrates. This global hypermethylation includes transposable elements and the bodies of genes at all expression levels. Significantly, we document an inverse relationship between TSS methylation and expression in the elephant shark, supporting the presence of the repressive regulatory architecture shared by higher vertebrates. Conclusions Our demonstration that methylation patterns in a cartilaginous fish are characteristic of higher vertebrates imply the conservation of this epigenetic modification system across jawed vertebrates separated by 465 million years of evolution. In addition, these findings position the elephant shark as a valuable model to explore the evolutionary history and function of vertebrate methylation.
Project description:The study reported here is the first characterization of elephant serum proteome in response to TB. These results advance our understanding of elephant immune response to M. tuberculosis and provide potential biomarkers for diagnosis and control of TB in this endangered species.
Project description:Analyses of ancient DNA typically involve sequencing the surviving short oligonucleotides, and aligning to genome assemblies from related, modern species. Here, we report that skin from a female woolly mammoth (†Mammuthus primigenius) which died 52,000 years ago retained its ancient genome architecture. We use PaleoHi-C to map chromatin contacts and assemble its genome, yielding twenty-eight chromosome-length scaffolds. Chromosome territories, compartments, loops, Barr bodies, and inactive-X chromosome (Xi) superdomains persist. The active and inactive genome compartments in mammoth skin more closely resemble Asian elephant skin than other elephant tissues. Our analyses uncover new biology. Differences in compartmentalization reveal genes whose transcription was potentially altered in mammoths vs. elephants. Mammoth Xi has a tetradic architecture, not bipartite like human and mouse. We hypothesize that, shortly after this mammoth’s death, the sample spontaneously freeze-dried in the Siberian cold, leading to a glass transition that preserved subfossils of ancient chromosomes at nanometer scale.
Project description:Chemical communication in elephants has been studied in detail both at the chemical and at the behavioural levels. Several pheromones have been identified, and their specific effects on the sexual behaviour of both the African and the Asian elephants have been accurately documented. This work is focused on the characterization of OBP1 through ligand-binding studies and analysis of post-translational modifications (PTMs). First, we have performed a proteomic analysis of a crude extract of the trunk wash obtained from the African elephant, and have found OBP1 as the main component, together with minor amounts of a OBP1 isoform and the von Ebner's gland (VEG) protein. Proteomic analysis of OBP1 revealed the occurrence of a variable degree of O-glycosylation, phosphorylation and acetylation in this protein. To specifically assay OBP1 spectra of binding, we have then expressed the African elephant protein in Pichia pastoris, which showed PTMs very similar to the natural counterpart. At functional level, we have found that recombinant OBP1 from the African elephant is able to bind the sex pheromone (Z)-7-dodecenyl acetate with strong affinity and some structurally related esters with lower strength.