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Recurrent Horizontal Transfer Identifies Mitochondrial Positive Selection in a Transmissible Cancer

Lookup NU author(s): Dr Thomas NichollsORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


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.

Publication metadata

Author(s): Strakova A, Nicholls TJ, Baez-Ortega A, Ní Leathlobhair M, Sampson AT, Hughes K, Bolton IAG, Gori K, Wang J, Airikkala-Otter I, Allen JL, Allum KM, Arnold CL, Bansse-Issa L, Bhutia TN, Bisson JL, Blank K, Briceño C, Castillo Domracheva A, Corrigan AM, Cran HR, Crawford JT, Cutter SM, Davis E, de Castro KF, De Nardi AB, de Vos AP, Keenan LD, Donelan EM, Espinoza Huerta AR, Faramade IA, Fazil A, Fotopoulou E, Fruean SN, Gallardo-Arrieta F, Glebova O, Gouletsou PG, Häfelin Manrique RF, Henriques JJGP, Horta RS, Ignatenko N, Kane Y, King C, Koenig D, Krupa A, Kruzeniski SJ, Lanza-Perea M, Lazyan M, Lopez Quintana AM, Losfelt T, Marino G, Martínez Castañeda S, Martínez-López MF, Masuruli BM, Meyer M, Migneco EJ, Nakanwagi B, Neal KB, Neunzig W, Nixon SJ, Ortega-Pacheco A, Pedraza-Ordoñez F, Peleteiro MC, Polak K, Pye RJ, Ramirez-Ante JC, Reece JF, Rojas Gutierrez J, Sadia H, Schmeling SK, Shamanova O, Sherlock AG, Steenland-Smit AE, Svitich A, Tapia Martínez LJ, Ngoka IT, Torres CG, Tudor EM, van der Wel MG, Vitalaru BA, Vural SA, Walkinton O, Wehrle-Martinez AS, Widdowson SAE, Zvarich I, Chinnery PF, Falkenberg M, Gustafsson CM, Murchison EP

Publication type: Article

Publication status: Published

Journal: Nature Communications

Year: 2020

Volume: 11

Online publication date: 16/06/2020

Acceptance date: 26/05/2020

Date deposited: 29/06/2020

ISSN (electronic): 2041-1723

Publisher: Nature Publishing Group


DOI: 10.1038/s41467-020-16765-w

PubMed id: 32546718


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Funder referenceFunder name
213464/Z/18/ZWellcome Trust
7761The Historic Building & Monuments Commission for England
European Research Council
Evelyn Trust and the National Institute for Healt Research (NIHR) Biomedical Research Centre
M811Rosetrees Trust
Knut and Alice Wallenberg Foundation
Swedish Research Council
Philip Leverhulme Prize for the Leverhulme Trust
Ruth Bowden Scholarship
Swedish Cancer Foundation