Recurrent horizontal transfer identifies mitochondrial positive selection in a transmissible cancer.
Andrea StrakovaThomas J NichollsAdrian Baez-OrtegaMáire Ní LeathlobhairAlexander T SampsonKatherine HughesIsobelle A G BoltonKevin GoriJinhong WangIlona Airikkala-OtterJanice L AllenKaren M AllumClara L ArnoldLeontine Bansse-IssaThinlay N BhutiaJocelyn L BissonKelli BlankCristóbal BriceñoArtemio Castillo DomrachevaAnne M CorriganHugh R CranJane T CrawfordStephen M CutterEric DavisKarina F de CastroAndrigo Barboza De NardiAnna P de VosLaura Delgadillo KeenanEdward M DonelanAdela R Espinoza HuertaIbikunle A FaramadeMohammed FazilEleni FotopoulouSkye N FrueanFanny Gallardo-ArrietaOlga GlebovaPagona G GouletsouRodrigo F Häfelin ManriqueJoaquim J G P HenriquesRodrigo Dos Santos HortaNatalia IgnatenkoYaghouba KaneCathy KingDebbie KoenigAda KrupaSteven J KruzeniskiMarta Lanza-PereaMihran LazyanAdriana M Lopez QuintanaThibault LosfeltGabriele MarinoSimón Martínez CastañedaMayra Fernanda Martínez-LópezBedan M MasuruliMichael MeyerEdward J MignecoBerna NakanwagiKarter B NealWinifred NeunzigSally J NixonAntonio Ortega-PachecoFrancisco Pedraza-OrdoñezMaria da Conceição PeleteiroKatherine PolakRuth J PyeJuan C Ramirez-AnteJohn F ReeceJose Rojas GutierrezHaleema SadiaSheila K SchmelingOlga ShamanovaAlan G SherlockAudrey E Steenland-SmitAlla SvitichLester J Tapia MartínezIsmail Thoya NgokaCristian G TorresElizabeth M TudorMirjam G van der WelBogdan A VițălaruSevil Atalay VuralOliver WalkintonAlvaro S Wehrle-MartinezSophie A E WiddowsonIrina ZvarichPatrick F ChinneryMaria FalkenbergClaes M GustafssonElizabeth P MurchisonPublished in: Nature communications (2020)
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.
Keyphrases
- mitochondrial dna
- copy number
- genome wide
- induced apoptosis
- papillary thyroid
- cell cycle arrest
- oxidative stress
- squamous cell
- transcription factor
- gene expression
- squamous cell carcinoma
- cell death
- dna damage
- minimally invasive
- dna repair
- signaling pathway
- lymph node metastasis
- young adults
- human health
- electron transfer