Transmissible Cancer Group, Department of Veterinary Medicine, University of Cambridge, Cambridge, UK.
Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK.
Science. 2023 Apr 21;380(6642):283-293. doi: 10.1126/science.abq6453. Epub 2023 Apr 20.
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 , 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.
袋獾产生了两种可传播的癌症谱系，分别命名为恶魔面部肿瘤 1（DFT1）和恶魔面部肿瘤 2（DFT2）。我们通过分析 78 个 DFT1 和 41 个 DFT2 基因组与新组装的染色体水平参考基因组，研究了这些克隆的遗传多样性和进化。时间分辨的系统发育树揭示了 DFT1 最早出现在 1986 年（1982 年至 1989 年），DFT2 出现在 2011 年（2009 年至 2012 年）。亚克隆分析记录了异质细胞群体的传播。DFT2 的突变率在所有变异类别的速度都比 DFT1 快，包括替换、插入、重排、转座元件插入和拷贝数改变，我们还鉴定出一个具有缺陷 DNA 错配修复的超突变 DFT1 谱系。几个位点在 DFT1 或 DFT2 中显示出可能的正选择证据，包括染色体 Y 的丢失和 的失活，但没有一个是两种癌症共有的。本研究揭示了两种在袋獾中共同栖息的可传播癌症的平行长期进化。
