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1.
Nat Commun ; 11(1): 3059, 2020 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-32546718

RESUMO

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.


Assuntos
DNA Mitocondrial/genética , Doenças do Cão/genética , Haplótipos , Tumores Venéreos Veterinários/genética , Animais , Cães , Transferência Genética Horizontal , Filogenia , Polimorfismo Genético , Recidiva , Seleção Genética
2.
Elife ; 52016 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-27185408

RESUMO

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.


Assuntos
Doenças do Cão/genética , Variação Genética , Mitocôndrias/genética , Recombinação Genética , Seleção Genética , Tumores Venéreos Veterinários/genética , Animais , DNA Mitocondrial/química , DNA Mitocondrial/genética , Cães , Análise de Sequência de DNA
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