Tasmanian devil facial tumour disease: too good a match for the immune system

By Hilary Miller 13/04/2010 1


ResearchBlogging.org
A central premise in conservation genetics is that high genetic diversity is good for a species’ continued survival, and low genetic diversity is bad. This seems intuitively obvious (after all, we all know that you shouldn’t marry your cousin) but actually finding examples in nature where we can say for sure that low genetic diversity has contributed to a population’s demise is difficult.   

However, the recent decline of tasmanian devil populations due to disease provides an excellent example of the perils of low genetic diversity.  Wild devil populations in eastern Tasmania have been decimated in recent years by devil facial tumour disease (DFTD).  This nasty disease is a transmissible cancer spread by biting, and causes large tumours to form around the mouth, interferring with feeding and eventually causing death.  Kathy Belov’s group at the University of Sydney has been studying the genetic basis of DFTD susceptibility in devils and has found that a lack of variation in immune system genes is responsible for the spread of the cancer in some populations.    

Tasmanian devil with facial tumour disease (photo: Menna Jones)

Belov’s group has been studying the genes of the Major Histocompatibility Complex, or MHC.  MHC molecules are a crucial part of the immune system in vertebrates, as they are responsible for recognising foreign invaders and mounting an immune response.  MHC molecules are also an important part of the process of self/non-self recognition that prevents the immune system attacking the body’s own cells.  MHC genes are normally highly variable in populations, with a large number of different alleles (or variants) for each gene.  This variability allows for a wide array of foreign pathogens to be resisted and accounts for differences in disease resistance among individuals.  Thus, populations with low or no variation at MHC genes are potentially susceptible to disease epidemics, as all individuals in the population will be equally susceptible to novel diseases.   

Devil populations in eastern Tasmania have low levels of genetic diversity due to reductions in population size over the last 150 years.  DFTD is so virulent in these populations because the tumours have the same MHC type as healthy devil cells.  Being an infectious cancer, transmission of DFTD between individuals is a bit like a skin graft or organ transplant. If the tissue’s MHC type matches, the transplant is accepted, if not it is rejected.  Because the MHC types of the tumour and the devil match, DFTD cells are not recognised as foreign so no immune response is mounted.  And because of the low genetic diversity, all devils in the population have similar MHC types meaning the disease can easily spread from one individual to another. 

DFTD has spread rapidly throughout eastern Tasmanian populations, causing a 90% decline in total devil numbers.  However, a population at West Pencil Pine in northwestern Tasmania has much lower prevalence of DFTD, suggesting this population harbours animals that are resistant to the disease.  New research by Belov’s lab published in Proceedings of the Royal Society of London last month shows that these populations have differences in their MHC makeup that appear to allow them to resist the disease. 

Here the story gets a little (more) complicated: Tasmanian devils have multiple MHC genes (up to 7 genes each), which fall into two groups on the basis of their DNA sequence.  The tumour cells have both group 1 and group 2 variants, as do the individuals from the susceptible eastern populations.  However the northwestern populations harbour a greater diversity of MHC types, and many individuals from these populations have MHC types which have only either group 1 or group 2 sequences.  None of these individuals have succumbed to DFTD, suggesting they are resistant to the disease.  Belov’s group proposes that in individuals with only group 1 sequences, the immune system will recognise the group 2 sequences on the tumour as foreign and resist it (and vice versa for individuals with only group 2 sequences).   This has yet to be tested in practice, as it is obviously difficult to get permission to infect an endangered species with a deadly disease.  However, these findings are promising for the continued survival of the species and may have a significant impact on their conservation management.

Siddle HV, Kreiss A, Eldridge MD, Noonan E, Clarke CJ, Pyecroft S, Woods GM, & Belov K (2007). Transmission of a fatal clonal tumor by biting occurs due to depleted MHC diversity in a threatened carnivorous marsupial. Proceedings of the National Academy of Sciences of the United States of America, 104 (41), 16221-6 PMID: 17911263

Siddle, H., Marzec, J., Cheng, Y., Jones, M., & Belov, K. (2010). MHC gene copy number variation in Tasmanian devils: implications for the spread of a contagious cancer Proceedings of the Royal Society B: Biological Sciences DOI: 10.1098/rspb.2009.2362


One Response to “Tasmanian devil facial tumour disease: too good a match for the immune system”

  • For Dunedinites: Assoc. Prof. Kathy Belov will be visiting Otago University on Thursday the 22nd of April, and will be giving a seminar at 4 pm in the Hutton Lecture Theatre.