Recurrent horizontal transfer identifies mitochondrial positive selection in a transmissible cancer

Autonomous replication and segregation of mitochondrial DNA (mtDNA) creates the potential for evolutionary conflict driven by emergence of haplotypes under positive selection for 'selfish' traits, such as replicative advantage. However, few cases of this phenomenon arising within natural populations have been described. Here, we survey the frequency of mtDNA horizontal transfer within the canine transmissible venereal tumour (CTVT), a contagious cancer clone that occasionally acquires mtDNA from its hosts. Remarkably, one canine mtDNA haplotype, A1d1a, has repeatedly and recently colonised CTVT cells, recurrently replacing incumbent CTVT haplotypes. An A1d1a control region polymorphism predicted to influence transcription is fixed in the products of an A1d1a recombination event and occurs somatically on other CTVT mtDNA backgrounds. We present a model whereby 'selfish' positive selection acting on a regulatory variant drives repeated fixation of A1d1a within CTVT cells.Wellcome 102942/Z/13/A Philip Leverhulme Prize from the Leverhulme Trust Kennel Club Charitable Trust European Molecular Biology Organization (EMBO) 7761 Ruth Bowden Scholarship from the British Federation of Women Graduates Wellcome Trust 213464/Z/18/Z Sir Henry Dale Fellowship - Royal Society 213464/Z/18/Z Rosetrees and Stoneygate Trust Research Fellowship M811 Swedish Research Council Swedish Cancer Foundation European Research Council (ERC) Knut & Alice Wallenberg Foundation Medical Research Council Mitochondrial Biology Unit MC_UP_1501/2 Evelyn Trust National Institute for Health Research (NIHR) NHS Foundation Trust University of Cambridg