The evolution of two transmissible cancers in Tasmanian devils

Abstract

AbstractTasmanian 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 (1982-1989), and DFT2 in 2011 (2009-2012). 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 illuminates the parallel long-term evolution of two transmissible cancers inhabiting a common niche in Tasmanian devils.