title: Mitochondrial genetic diversity, selection and recombination in a canine transmissible cancer.
abstract: 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 distributions 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 a driver of CTVT global metastatic spread, further highlighting the important role of mtDNA in cancer evolution.
authors.affiliation: Department of Veterinary Medicine, University of Cambridge, Cambridge, United Kingdom.
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authors.affiliation: Department of Veterinary Medicine, University of Cambridge, Cambridge, United Kingdom.
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authors.affiliation: State Key Laboratory of Genetic Resources and Evolution, Yunnan Laboratory of Molecular Biology of Domestic Animals, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China.
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authors.initials: GD
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Genetic Resources and Evolution, Yunnan Laboratory of Molecular Biology of Domestic Animals, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China.
authors.forename: Ting-Ting
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authors.identifier: 0000-0001-7462-8907
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mesh_terms: D000818:Animals; D004272:DNA, Mitochondrial / Q000737:chemistry / Q000235:genetics; D004283:Dog Diseases / Q000235:genetics*; D004285:Dogs; D014644:Genetic Variation; D008928:Mitochondria / Q000235:genetics*; D011995:Recombination, Genetic; D012641:Selection, Genetic; D017422:Sequence Analysis, DNA; D014685:Venereal Tumors, Veterinary / Q000235:genetics*
chemical_list: D004272:DNA, Mitochondrial
keywords: Dog; cancer biology; canine transmissible venereal tumour; evolutionary biology; genomics; mitochondria; transmissible cancer