Transmissible Cancers in Tasmanian Devils Evolved in Parallel, Genomic Analysis Shows

A survey of the genomes of two lineages of transmissible facial cancer that threaten Tasmanian devils has illuminated the evolutionary history of these unusual pathogens. "Our analysis suggests that Tasmanian devils host a cell type that is poised for transmissible cancer transformation," say Maximillian Stammnitz and colleagues. "Once established, [the transmissible facial cancer] clones continue to acquire mutations at constant rates, and, although most of these are neutral, a small subset drive further adaptation to the niche." Transmissible cancers are contagious cancers that spread via the transfer of living cancer cells. Although rare in nature, Tasmanian devils (Sarcophilus harrisii) are known to harbor at least two transmissible cancer lineages: devil facial tumor 1 (DFT1) and devil facial tumor 2 (DFT2), which were first observed in the wild in 1996 and 2014, respectively. Already threatened by habitat loss and other human impacts, Tasmanian devil populations have been severely impacted by these diseases, leading to conservation concerns. However, the origin, genetic diversity, and long-term evolution of these two transmissible cancer clones is poorly understood, and previous Tasmanian devil genome assemblies used to evaluate related questions have been highly fragmented. Stammnitz and colleagues present a high-coverage whole-genome analysis of 119 DFT1 and DFT2 tumors. They evaluated genetic diversity of these clones by comparing their genomes to that of a newly assembled, chromosome-level reference. Using time-resolved phylogenetic trees, Stammnitz et al. estimate that DFT1 likely first emerged during the 1980s and DFT2 in 2011. Although the two cancers are highly genetically similar, the authors discovered that DFT2 has a significantly higher mutation rate than DFT1 across all variant classes, which could have complex epidemiological implications. While the future trajectories of DFT lineages and their Tasmanian devil hosts remain uncertain, this study "provides a vantage point from which to further explore the evolution and impacts of transmissible cancers in this iconic marsupial species," say the authors.