Tasmanian devils have spawned two transmissible cancer lineages, named devil facial tumour 1 (DFT1) and devil facial tumour 2 (DFT2). We investigated the genetic diversity and evolution of these clones by analysing 78 DFT1 and 41 DFT2 genomes relative to a newly assembled, chromosome-level reference. Time-resolved phylogenetic trees reveal that DFT1 first emerged in 1986 (1982 to 1989) and DFT2 in 2011 (2009 to 2012). Subclone analysis documents transmission of heterogeneous cell populations. DFT2 has faster mutation rates than DFT1 across all variant classes, including substitutions, indels, rearrangements, transposable element insertions, and copy number alterations, and we identify a hypermutated DFT1 lineage with defective DNA mismatch repair. Several loci show plausible evidence of positive selection in DFT1 or DFT2, including loss of chromosome Y and inactivation of MGA, but none are common to both cancers. This study reveals the parallel long-term evolution of two transmissible cancers inhabiting a common niche in Tasmanian devils.
Maximilian R. Stammnitz 1, Kevin Gori 1, Young Mi Kwon 1, Edward Harry 2, Fergal J. Martin 3 , Konstantinos Billis 3, Yuanyuan Cheng 4, Adrian Baez-Ortega 1, William Chow 2, Sebastien Comte 5,6, Hannes Eggertsson 7 , Samantha Fox 8,9, Rodrigo Hamede 5,10, Menna Jones 5 , Billie Lazenby 8, Sarah Peck 8, Ruth Pye 11 , Michael A. Quail 2, Kate Swift 12, Jinhong Wang 1, Jonathan Wood 2, Kerstin Howe 2 , Michael R. Stratton 2, Zemin Ning 2, and Elizabeth P. Murchison 1.
Science, 2023 Apr 20, 380 (6642): 283-293, doi: 10.1126/science. abq6453
1Transmissible Cancer Group, Department of Veterinary Medicine, University of Cambridge, Cambridge, UK.
2 Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK.
3European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK.
4School of Life and Environmental Sciences, University of Sydney, Sydney, NSW, Australia.
5School of Natural Sciences, University of Tasmania, Hobart, TAS, Australia.
6Vertebrate Pest Research Unit, NSW Department of Primary Industries, Orange, NSW, Australia.
7deCODE Genetics Inc., Reykjavik, Iceland.
8Save the Tasmanian Devil Program, Tasmanian Department of Natural Resources and Environment, Hobart, TAS, Australia.
9Toledo Zoo, Toledo, OH, USA.
10CANCEV, Centre de Recherches Ecologiques et Evolutives sur le Cancer, Montpellier, France.
11Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia
12Mount Pleasant Laboratories, Tasmanian Department of Natural Resources and Environment, Prospect, TAS, Australia.