MHC gene copy number variation in Tasmanian devils: implications for the spread of a contagious cancer

Abstract

Tasmanian devils face extinction owing to the emergence of a contagious cancer. Devil facial tumour disease (DFTD) is a clonal cancer spread owing to a lack of major histocompatibility complex (MHC) barriers in Tasmanian devil populations. We present a comprehensive screen of MHC diversity in devils and identify 25 MHC types and 53 novel sequences, but conclude that overall levels of MHC diversity at the sequence level are low. The majority of MHC Class I variation can be explained by allelic copy number variation with two to seven sequence variants identified per individual. MHC sequences are divided into two distinct groups based on sequence similarity. DFTD cells and most devils have sequences from both groups. Twenty per cent of individuals have a restricted MHC repertoire and contain only group I or only group II sequences. Counterintuitively, we postulate that the immune system of individuals with a restricted MHC repertoire may recognize foreign MHC antigens on the surface of the DFTD cell. The implication of these results for management of DFTD and this endangered species are discussed.

A second transmissible cancer in Tasmanian devils

“…This could perhaps be mediated by this this species' apparent elevated susceptibility to neoplasia (21,22), low genetic diversity (10,(23)(24)(25), and/or biting behavior (26). However, if this is the case, it is surprising that tumors comparable with DFTD were not reported before 1996 (4,5).…”

Disease and the dynamics of extinction

“…In the case of Tasmanian devils, the cancer has been able to spread through populations in the eastern part of the island because of extraordinarily low MHC diversity [47], such that recipient devils are unable to recognize tumour cells from another animal as 'non-self '. In the northwest of the island, which is only now being invaded by the tumour, there is a greater variety of MHC types [73]. Furthermore, there is evidence that the epidemiology of the tumour is different in the northwest from eastern Tasmania, with slower increase in prevalence through time and fewer effects on the age structure of the devil population [104].…”

“…The disease manifests as large tumours, particularly around the head of the affected animal, and is inevitably fatal once clinical signs are apparent [75,76]. In populations with MHC types similar to the tumour [73], prevalence increases rapidly after the initial arrival of the disease, affecting the majority of the adult population within 3-4 years ( figure 3). Prevalence remains very high (in excess of 50% in susceptible age classes) even after major population declines (figure 4), suggesting that the disease has a very low density threshold [41].…”

“…Tasmanian DFTD is threatening a species that, until the appearance of disease, appeared to be secure and increasing in numbers. However, extremely low genetic diversity, possibly as a result of a previous selective sweep [47,73], has predisposed the species to be susceptible to an allograft.…”

“…DFTD is spread by biting, which occurs frequently in sexual encounters and disputes over food. Tumour cells appear not to be rejected by recipient devils because of the very low genetic diversity in devil populations, particularly even in the major histocompatibility complex (MHC), to the extent that cells from another devil are not recognized as 'foreign' [47,73], although recent work suggests that the tumour cells also have some ability to evade the host's immune system [74]. Since its first appearance in northeastern Tasmania in 1996, the infection has spread across most of the range of Tasmanian devils, causing population declines of up to 90 per cent in affected populations [69].…”