Recurrent horizontal transfer identifies mitochondrial positive selection in a transmissible cancer

ANTONIO ORTEGA PACHECO; JOSE SIMON MARTINEZ CASTAÑEDA; ANDREA STRAKOVA; THOMAS J. NICHOLLS; ADRIAN BAEZ ORTEGA; MAIRE NI LEATHLOBHAIR; ALEXANDER T. SAMPSON; KATHERINE HUGHES; ISOBELLE A. G. BOLTON; KEVIN GORI; JINHONG WANG; ILONA AIRIKKALA OTTER; JANICE L. ALLEN; KAREN M. ALLUM; CLARA L. ARNOLD; LEONTINE BANSSE ISSA; THINLAY N. BHUTIA; JOCELYN L. BISSON; KELLI BLANK; CRISTOBAL BRICEÑO; ARTEMIO CASTILLO DOMRACHEVA; ANNE M. CORRIGAN; HUGH R. CRAN; JANE T. CRAWFORD; STEPHEN M. CUTTER; ERIC DAVIS; ANDRIGO B. DE NARDI; ANNA P. DE VOS; LAURA DELGADILLO KEENAN; EDWARD M. DONELAN; ADELA R. ESPINOZA HUERTA; IBIKUNLE A. FARAMADE; MOHAMMED FAZIL; ELENI FOTOPOULOU; SKYE N. FRUEAN; FANNY GALLARDO ARRIETA; OLGA GLEBOVA; PAGONA G. GOULETSOU; RODRIGO F. HAFELIN MANRIQUE; JOAQUIM J. G. P. HENRIQUES; RODRIGO S. HORTA; NATALIA IGNATENKO; YAGHOUBA KANE; CATHY KING; DEBBIE KOENIG; ADA KRUPA; STEVEN J. KRUZENISKI; MARTA LANZA PEREA; MIHRAN LAZYAN; ADRIANA M. LOPEZ QUINTANA; THIBAULT LOSFELT; GABRIELE MARINO; MAYRA F. MARTINEZ LOPEZ; BEDAN M. MASURULI; MICHAEL MEYER; EDWARD J. MIGNECO; BERNA NAKANWAGI; KARTER B. NEAL; WINIFRED NEUNZIG; SALLY J. NIXON; FRANCISCO PEDRAZA ORDOÑEZ; MARIA C. PELETEIRO; KATHERINE POLAK; RUTH J. PYE; JUAN C. RAMIREZ ANTE; JOHN F. REECE; JOSE ROJAS GUTIERREZ; HALEEMA SADIA; SHEILA K. SCHMELING; OLGA SHAMANOVA; ALAN G. SHERLOCK; AUDREY E. STEENLAND SMIT; ALLA SVITICH; LESTER J. TAPIA MARTINEZ; ISMAIL THOYA NGOKA; CRISTIAN G. TORRES; ELIZABETH M. TUDOR; MIRJAM G. VAN DER WEL; BODGAN A. VITALARU; SEVIL A. VURAL; OLIVER WALKINTON; ALVARO S. WEHRLE MARTINEZ; SOPHIE A. E. WIDDOWSON; IRINA ZVARICH; PATRICK F. CHINNERY; MARIA FALKENBERG; CLAES M. GUSTAFSSON; ELIZABETH P. MURCHISON

Recurrent horizontal transfer identifies mitochondrial positive selection in a transmissible cancer

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.

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