Evolution and lineage dynamics of a transmissible cancer in Tasmanian devils
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Gori, Kevin1
- Kwon, Young Mi1
- Park, Naomi2
- Potts, Nicole1
- Swift, Kate3
- Wang, Jinhong1
- Stammnitz, Maximilian R1
- Cannell, Naomi1
- Baez-Ortega, Adrian1
- Comte, Sebastien4
- Fox, Samantha5
- Jones, Menna4
- Kreiss, Alexandre6
- Lawrence, Clare5
- Lazenby, Billie5
- Peck, Sarah5
- Pye, Ruth6
- Zimmermann, Mona1
- Woods, Gregory6
- Wedge, David7
- Pemberton, David5
- Stratton, Michael R2
- Hamede, Rodrigo4
- Murchison, Elizabeth P1
- 1. Transmissible Cancer Group, Department of Veterinary Medicine, University of Cambridge, Cambridge CB3 0ES, United Kingdom
- 2. Wellcome Sanger Institute, Hinxton CB10 1SA, United Kingdom
- 3. Mount Pleasant Laboratories, Tasmanian Department of Primary Industries, Parks, Water and the Environment (DPIPWE), Prospect, Tasmania 7250, Australia
- 4. School of Natural Sciences, University of Tasmania, 55 Private Bag, Hobart, Tasmania 7000, Australia
- 5. Tasmanian Department of Primary Industries, Parks, Water and the Environment (DPIPWE), Save the Tasmanian Devil Program, Tasmania 7000, Australia
- 6. Menzies Institute, University of Tasmania, 17 Liverpool Street, Hobart, Tasmania 7000, Australia
- 7. Oxford Big Data Institute, University of Oxford, Oxford, United Kingdom
Description
Devil facial tumour 1 (DFT1) is a transmissible cancer clone endangering the Tasmanian devil. The expansion of DFT1 across Tasmania has been documented, but little is known of its evolutionary history. We analysed genomes of 648 DFT1 tumours collected throughout the disease range between 2003 and 2018. DFT1 diverged early into five clades, three spreading widely and two failing to persist. One clade has replaced others at several sites, and rates of DFT1 co-infection are high. DFT1 gradually accumulates copy number variants (CNVs) and its telomere lengths are short but constant. Recurrent CNVs reveal genes under positive selection, sites of genome instability and repeated loss of a small derived chromosome. Cultured DFT1 cell lines have increased CNV frequency and undergo highly reproducible convergent evolution. Overall, DFT1 is a remarkably stable lineage whose genome illustrates how cancer cells adapt to diverse environments and persist in a parasitic niche.