The evolution of two transmissible cancers in Tasmanian devils

Author:

Stammnitz Maximilian R.1ORCID,Gori Kevin1ORCID,Kwon Young Mi1ORCID,Harry Edward2ORCID,Martin Fergal J.3ORCID,Billis Konstantinos3ORCID,Cheng Yuanyuan4ORCID,Baez-Ortega Adrian1,Chow William2ORCID,Comte Sebastien56ORCID,Eggertsson Hannes7ORCID,Fox Samantha89ORCID,Hamede Rodrigo510ORCID,Jones Menna5ORCID,Lazenby Billie8ORCID,Peck Sarah8,Pye Ruth11ORCID,Quail Michael A.2ORCID,Swift Kate12ORCID,Wang Jinhong1ORCID,Wood Jonathan2ORCID,Howe Kerstin2ORCID,Stratton Michael R.2,Ning Zemin2,Murchison Elizabeth P.1ORCID

Affiliation:

1. Transmissible Cancer Group, Department of Veterinary Medicine, University of Cambridge, Cambridge, UK.

2. Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK.

3. European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK.

4. School of Life and Environmental Sciences, University of Sydney, Sydney, NSW, Australia.

5. School of Natural Sciences, University of Tasmania, Hobart, TAS, Australia.

6. Vertebrate Pest Research Unit, NSW Department of Primary Industries, Orange, NSW, Australia.

7. deCODE Genetics Inc., Reykjavik, Iceland.

8. Save the Tasmanian Devil Program, Tasmanian Department of Natural Resources and Environment, Hobart, TAS, Australia.

9. Toledo Zoo, Toledo, OH, USA.

10. CANCEV, Centre de Recherches Ecologiques et Evolutives sur le Cancer, Montpellier, France.

11. Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia.

12. Mount Pleasant Laboratories, Tasmanian Department of Natural Resources and Environment, Prospect, TAS, Australia.

Abstract

Tasmanian devils have spawned two transmissible cancer lineages, named devil facial tumor 1 (DFT1) and devil facial tumor 2 (DFT2). We investigated the genetic diversity and evolution of these clones by analyzing 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.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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