SciCombinator

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Concept: Tasmanian Devil

195

Tasmanian devil joeys, like other marsupials, are born at a very early stage of development, prior to the development of their adaptive immune system, yet survive in a pathogen-laden pouch and burrow. Antimicrobial peptides, called cathelicidins, which provide innate immune protection during early life, are expressed in the pouch lining, skin and milk of devil dams. These peptides are active against pathogens identified in the pouch microbiome. Of the six characterised cathelicidins, Saha-CATH5 and 6 have broad-spectrum antibacterial activity and are capable of killing problematic human pathogens including methicillin-resistant S. aureus and vancomycin-resistant E. faecalis, while Saha-CATH3 is active against fungi. Saha-CATH5 and 6 were toxic to human A549 cells at 500 μg/mL, which is over seven times the concentration required to kill pathogens. The remaining devil cathelicidins were not active against tested bacterial or fungal strains, but are widely expressed throughout the body, such as in immune tissues, in digestive, respiratory and reproductive tracts, and in the milk and pouch, which indicates that they are likely also important components of the devil immune system. Our results suggest cathelicidins play a role in protecting naive young during pouch life by passive immune transfer in the milk and may modulate pouch microbe populations to reduce potential pathogens.

Concepts: Immune system, Bacteria, Microbiology, Innate immune system, Adaptive immune system, Marsupial, Tasmanian Devil, Dasyuridae

171

Devil facial tumour disease (DFTD) is a fatal contagious cancer that has decimated Tasmanian devil populations. The tumour has spread without invoking immune responses, possibly due to low levels of Major Histocompatibility Complex (MHC) diversity in Tasmanian devils. Animals from a region in north-western Tasmania have lower infection rates than those in the east of the state. This area is a genetic transition zone between sub-populations, with individuals from north-western Tasmania displaying greater diversity than eastern devils at MHC genes, primarily through MHC class I gene copy number variation. Here we test the hypothesis that animals that remain healthy and tumour free show predictable differences at MHC loci compared to animals that develop the disease.

Concepts: Immune system, Gene, Genetics, Major histocompatibility complex, MHC class I, Tasmania, Devil facial tumour disease, Tasmanian Devil

159

Tasmanian devils (Sarcophilus harrisii) risk extinction from a contagious cancer, devil facial tumour disease (DFTD) in which the infectious agent is the tumor cell itself. Because devils are unable to produce an immune response against the tumor cells no devil has survived ‘infection’. To promote an immune response we immunized healthy devils with killed DFTD tumor cells in the presence of adjuvants. Immune responses, including cytotoxicity and antibody production, were detected in five of the six devils. The incorporation of adjuvants that act via toll like receptors may provide additional signals to break ‘immunological ignorance’. One of these devils was protected against a challenge with viable DFTD cells. This was a short-term protection as re-challenge one year later resulted in tumor growth. These results suggest that Tasmanian devils can generate immune responses against DFTD cells. With further optimization of immune stimulation it should be possible to protect Tasmanian devils against DFTD with an injectable vaccine.

Concepts: Immune system, Antibody, Cancer, Infectious disease, Vaccination, Immunology, Devil facial tumour disease, Tasmanian Devil

85

The last known Tasmanian tiger (Thylacinus cynocephalus)-aka the thylacine-died in 1936. Because its natural behavior was never scientifically documented, we are left to infer aspects of its behavior from museum specimens and historical recollections of bushmen. Recent advances in brain imaging have made it possible to scan postmortem specimens of a wide range of animals, even more than a decade old. Any thylacine brain, however, would be more than 100 years old. Here, we show that it is possible to reconstruct white matter tracts in two thylacine brains. For functional interpretation, we compare to the white matter reconstructions of the brains of two Tasmanian devils (Sarcophilus harrisii). We reconstructed the cortical projection zones of the basal ganglia and major thalamic nuclei. The basal ganglia reconstruction showed a more modularized pattern in the cortex of the thylacine, while the devil cortex was dominated by the putamen. Similarly, the thalamic projections had a more orderly topography in the thylacine than the devil. These results are consistent with theories of brain evolution suggesting that larger brains are more modularized. Functionally, the thylacine’s brain may have had relatively more cortex devoted to planning and decision-making, which would be consistent with a predatory ecological niche versus the scavenging niche of the devil.

Concepts: Basal ganglia, Thalamus, Marsupial, Tasmania, Dingo, Tasmanian Devil, Dasyuromorphia, Dasyuromorphs

83

Devil facial tumour disease (DFTD) is a transmissible cancer devastating the Tasmanian devil (Sarcophilus harrisii) population. The cancer cell is the ‘infectious’ agent transmitted as an allograft by biting. Animals usually die within a few months with no evidence of antibody or immune cell responses against the DFTD allograft. This lack of anti-tumour immunity is attributed to an absence of cell surface major histocompatibility complex (MHC)-I molecule expression. While the endangerment of the devil population precludes experimentation on large experimental groups, those examined in our study indicated that immunisation and immunotherapy with DFTD cells expressing surface MHC-I corresponded with effective anti-tumour responses. Tumour engraftment did not occur in one of the five immunised Tasmanian devils, and regression followed therapy of experimentally induced DFTD tumours in three Tasmanian devils. Regression correlated with immune cell infiltration and antibody responses against DFTD cells. These data support the concept that immunisation of devils with DFTD cancer cells can successfully induce humoral responses against DFTD and trigger immune-mediated regression of established tumours. Our findings support the feasibility of a protective DFTD vaccine and ultimately the preservation of the species.

Concepts: Immune system, Antibody, Cancer, Oncology, Immunology, Tasmania, Devil facial tumour disease, Tasmanian Devil

49

Immunoglobulins such as IgG and IgM have been shown to induce anti-tumour cytotoxic activity. In the present study we therefore explore total serum IgG and IgM expression dynamics in 23 known-aged Tasmanian devils (Sarcophilus harrisii) of which 9 where affected by Devil Facial Tumour Disease (DFTD). DFTD is clonally transmissible cancer that has caused massive declines in devil numbers. Our analyses revealed that IgM and IgG expression levels as well as IgM/IgG ratios decreased with increasing devil age. Neither age, sex, IgM nor IgG expression levels affected devil DFTD status in our analyses. However, devils with increased IgM relative to IgG expression levels had significantly lower DFTD prevalence. Our results therefore suggest that IgM/IgG ratios may play an important role in determining devil susceptibility to DFTD. We consequently propose that our findings warrant further studies to elucidate the underpinning(s) of devil IgM/IgG ratios and DFTD status.

Concepts: Immune system, Cancer, Immunology, Tasmania, Devil facial tumour disease, Tasmanian Devil, Dasyuridae, Sarcophilus

40

The Tasmanian devil (Sarcophilus harrisii), the largest marsupial carnivore, is endangered due to a transmissible facial cancer spread by direct transfer of living cancer cells through biting. Here we describe the sequencing, assembly, and annotation of the Tasmanian devil genome and whole-genome sequences for two geographically distant subclones of the cancer. Genomic analysis suggests that the cancer first arose from a female Tasmanian devil and that the clone has subsequently genetically diverged during its spread across Tasmania. The devil cancer genome contains more than 17,000 somatic base substitution mutations and bears the imprint of a distinct mutational process. Genotyping of somatic mutations in 104 geographically and temporally distributed Tasmanian devil tumors reveals the pattern of evolution and spread of this parasitic clonal lineage, with evidence of a selective sweep in one geographical area and persistence of parallel lineages in other populations.

Concepts: DNA, Genetics, Cancer, Mutation, Tasmania, Devil facial tumour disease, Tasmanian Devil, Dasyuridae

38

The Tasmanian devil, the world’s largest carnivorous marsupial, is at risk of extinction due to devil facial tumour disease (DFTD), a fatal contagious cancer. The Save the Tasmanian Devil Program has established an insurance population, which currently holds over 600 devils in captive facilities across Australia. Microbes are known to play a crucial role in the health and well-being of humans and other animals, and increasing evidence suggests that changes in the microbiota can influence various aspects of host physiology and development. To improve our understanding of devils and facilitate management and conservation of the species, we characterised the microbiome of wild devils and investigated differences in the composition of microbial community between captive and wild individuals.

Concepts: Archaea, Conservation biology, Species, Mammal, Marsupial, Devil facial tumour disease, Tasmanian Devil, Thylacine

27

The Australian numbat, Myrmecobius fasciatus, is the only marsupial that feeds almost exclusively on termites and that has a life following the diurnally restricted and dynamic geographical distribution of termites. The millions of years of this adaptation led to unique morphological and anatomical features, especially basicranial and dental characteristics, that make it difficult to identify a clear phylogenetic affiliation to other marsupials. From DNA sequence analyses, the family Myrmecobiidae is placed within the dasyuromorph marsupials, but the exact position varies from study to study, and support values are mostly rather modest. Here we report the recovery and analysis of about 110,000 quasi-fossilized traces of mobile element insertions into the genome of a dasyurid marsupial (Tasmanian devil), 25 of which are phylogenetically informative for early dasyuromorphial evolution. Fourteen of these ancient retroposon insertions are shared by the 16 Dasyuromorphia species analyzed, including the numbat, but are absent in the outgroups. An additional 11 other insertions are present in all Dasyuridae, but are absent in the numbat. These findings place numbats as the sister group to all living Dasyuridae, and show that the investigated Dasyuromorphia, including the Myrmecobiidae, constitute a monophyletic group that is separated from Peramelemorphia, Notoryctemorphia and other marsupials.

Concepts: Phylogenetics, Marsupial, Tasmanian Devil, Dasyuromorphia, Dasyuridae, Numbat, Thylacine, Peramelemorphia

25

Inbreeding depression occurs when inbred individuals experience reduced fitness as a result of reduced genome-wide heterozygosity. The Tasmanian devil faces extinction due to a contagious cancer, devil facial tumour disease (DFTD). An insurance metapopulation was established in 2006 to ensure the survival of the species and to be used as a source population for re-wilding and genetic rescue. The emergence of DFTD and the rapid decline of wild devil populations have rendered the species at risk of inbreeding depression. We used 33 microsatellite loci to (1) reconstruct a pedigree for the insurance population and (2) estimate genome-wide heterozygosity for 200 individuals. Using heterozygosity-fitness correlations, we investigated the effect of heterozygosity on six diverse fitness measures (ulna length, asymmetry, weight-at-weaning, testes volume, reproductive success and survival). Despite statistically significant evidence of variation in individual inbreeding in this population, we found no associations between inbreeding and any of our six fitness measurements. We propose that the benign environment in captivity may decrease the intensity of inbreeding depression, relative to the stressful conditions in the wild. Future work will need to measure fitness of released animals to facilitate translation of this data to the broader conservation management of the species in its native range.

Concepts: Genetics, Evolution, Statistics, Extinction, Inbreeding, Inbreeding depression, Devil facial tumour disease, Tasmanian Devil