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.

Figure 1.

Map of Tasmania showing diversity of MHC types at sampling locations: 1, West Pencil Pine; 2, Edith Creek to Dip Falls; 3, Togari North to Christmas Hills; 4, Gunns Woolnorth; 5, Togari South to Salmon River Road; 6, Marrawah to Temma; 7, Strahan to Corinna; 8, Cape Sorrell; 9, Bronte Park; 10, Fentonbury; 11, Forestier; 12, Buckland to Nugent; 13, Freycinet; 14, Epping forest and 15, Mount William. There appear to be more MHC types in the northwest than in the east. The grey area on the map shows the core distribution of Tasmanian devils and the area to the right of the broken line is where DFTD has spread (DPIW 2008).