Abstract
BackgroundDevil 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.Methodology/Principal FindingsWe compared MHC class I sequences in 29 healthy and 22 diseased Tasmanian devils from West Pencil Pine, a population in north-western Tasmania exhibiting reduced disease impacts of DFTD. Amplified alleles were assigned to four loci, Saha-UA, Saha-UB, Saha-UC and Saha-UD based on recently obtained genomic sequence data. Copy number variation (caused by a deletion) at Saha-UA was confirmed using a PCR assay. No association between the frequency of this deletion and disease status was identified. All individuals had alleles at Saha-UD, disproving theories of disease susceptibility relating to copy number variation at this locus. Genetic variation between the two sub-groups (healthy and diseased) was also compared using eight MHC-linked microsatellite markers. No significant differences were identified in allele frequency, however differences were noted in the genotype frequencies of two microsatellites located near non-antigen presenting genes within the MHC.Conclusions/SignificanceWe did not find predictable differences in MHC class I copy number variation to account for differences in susceptibility to DFTD. Genotypic data was equivocal but indentified genomic areas for further study.
Highlights
The Tasmanian devil (Sarcophilus harrisii) is threatened with extinction in the wild due to the emergence of a contagious cancer known as Devil Facial Tumour Disease (DFTD)
We previously suggested that both the naturally existing contagious cancers, Devil facial tumour disease (DFTD) and Canine Transmissible Venereal Tumour (CTVT) evolved in populations of devils and wolves respectively that lacked Major Histocompatibility Complex (MHC) diversity [18]
We discover that mismatches in previously published polymerase chain reaction (PCR) primers result in inconsistent amplification of MHC alleles and turn to MHC-linked microsatellites to look for differences between the affected and unaffected groups, which proves to be an efficient alternative to cloning-andsequencing based MHC typing in investigating genetic diversity and natural selection at MHC loci [25,26,27]
Summary
The Tasmanian devil (Sarcophilus harrisii) is threatened with extinction in the wild due to the emergence of a contagious cancer known as Devil Facial Tumour Disease (DFTD). DFTD is invariably fatal, usually within 3–6 months of the clinical presentation of visible tumours [9]. This has clear impacts, not just on devil population size and growth rates [10], and age class structuring [11] and important life history traits including dispersal [12], sex ratios [11] and age at first reproduction [13]. Devil facial tumour disease (DFTD) is a fatal contagious cancer that has decimated Tasmanian devil populations. 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. 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
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