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Tasmanian devils’ transmissible : Izarbe Aísa Marín Bachelor’s Degree What is the future? Final Project | June 2017

Introduction Devil Facial Tumor Disease 1Why is Tasmanian devils’ cancer incidence so high? 2Introduction to transmissible is thought to occur via Peto’s Paradox represents the lack of accumulation of and correlation between cancer prevalence rates depend on number, which and body size or lifespan and it can be Primary Mode of Lack of Capacity for correlates with body size and lifespan. useful to explore cases that are far tumor’s origin transmission allorecognition infinite growth Then, large and long-lived from what is expected. Tasmanian should have more cancers than smaller devils suffer from Devil Facial Tumor and shorter-lived ones, due to increased Disease (DFTD), a lethal transmissible The ancestral type of DTDF is thought to be derived from a Schwann cell (clonal number of cell divisions. cancer that is threatening the species origin) and it is transmitted by biting during mating or feeding interactions. to extinction. (2) (1)

y = 0,0815 - 0,0061x [y=%Tumors; x=Log(Mass[x]*LifeSpan[y])]

10x

DFTD was first reported in Mount William National Park, northeastern Tasmania, in 1996. In 20 years, the disease has spread to more than 85% Forestier of wild Tasmanian devil Peninsula populations, causing severe declines.

Immunology of DFTD 3Why devils do not recognize DFTD? (3) Deficiency of devil Marsupials’ immune system is different immune system from, rather than inferior to mammals’ immune system.

Immunological Low genetic Slower immune responses tolerance diversity facilitate early transmission events.

MHC MHC is regulated by modifications affecting the downregulation state of β2m and TAP promoters

DFTD outcome Conclusions and Perspectives 4Prediction of DFTD based on comparative biology 5Is Tasmanian devil doomed to extinction? Dogs suffer from Canine Transmissible Venereal Tumor (CTVT). During the progressive phase the immune system does not recognize tumor due to down-regulation of MHC. Reduction of DFTD However, after a period, tumor begins to regress as a result of significant increase in MHC Attenuation of DFTD pathogenicity. expression. Tasmanian devil evolutionary Evidence of resistance response and regression. Parasite evolution Immunization with adjuvants Development of a vaccine and DFTD cells expressing Similarities Differences MHC. Both have suffered severe CTVT has had grater time population bottlenecks, to evolve than DFTD, and Although devils could evolve resistance to the disease, considering its much which caused low genetic devils’ populations have larger effective population sizes, it is more likely that the tumor evolve towards diversity and down- suffered from stronger an attenuation of virulence. regulation of MHC. decrease.

Conservation of Tasmanian devil

Infection in closely related Instability of DFTD cells Methods species NCBI Pubmed search by using keywords combined with the appropriated Boolean Co-evolution of the tumor Strong selection for less operators. To calculate devils’ cancer incidence I conducted a regression analysis and the lethal disease using Microsoft Excel.

References 1. Abegglen LM et al (2015). Potential mechanisms for cancer resistance in elephants and comparative cellular response to DNA damage in . JAMA 314:1850-60. 2. Bender HS, Marshall Graves JA, Deakin JE (2014). Pathogenesis and of a transmissible tumor in the Tasmanian devil. Annu Rev Anim Biosci 2:165-87. 3. Murchison EP (2009). Clonally transmissible cancers in dogs and Tasmanian devils. Suppl. 2:S19-S30.