Canine_Transmissible_Venereal_Tumour__CTVT__mitochondria. Canine_Transmissible_Venereal_Tumour__CTVT__mitochondria

Canine transmissible venereal tumour (CTVT) is a clonally transmissible cancer that originated approximately 11,000 years ago and affects dogs worldwide. Despite the clonal origin of the CTVT nuclear genome, CTVT mitochondrial genomes (mtDNAs) have been acquired by periodic capture from transient hosts. We sequenced 449 complete mtDNAs from a global population of CTVTs, and show that mtDNA horizontal transfer has occurred at least five times, delineating five tumour clades whose distribution track two millennia of dog global migration. Negative selection has operated to prevent accumulation of deleterious mutations in captured mtDNA, and recombination has caused occasional mtDNA re-assortment. These findings implicate functional mtDNA as drivers of CTVT global metastatic spread, further highlighting the important role of mtDNA in cancer evolution.

犬传染性生殖器官肿瘤（Canine transmissible venereal tumour, CTVT）是一种可克隆传播的癌症，约于11000年前起源，可感染全球各地的犬只。尽管CTVT的细胞核基因组均为克隆起源，但该肿瘤的线粒体基因组（mtDNA）却是通过周期性地从瞬时宿主中捕获获得。本研究对全球范围内449株CTVT的完整线粒体基因组进行了测序，结果显示线粒体DNA水平转移事件至少发生五次，由此界定出五个肿瘤进化枝，其分布轨迹与两千年来犬类的全球迁徙历程相契合。研究还发现，负选择可阻止捕获的mtDNA积累有害突变，而重组过程偶尔会引发线粒体DNA重排。上述研究结果表明，功能性mtDNA是CTVT实现全球转移扩散的驱动因素，进一步凸显了线粒体基因组在癌症演化中的重要作用。