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Mitochondrial genetic diversity, selection and recombination in a canine transmissible cancer

2016; eLife Sciences Publications Ltd; Volume: 5; Linguagem: Inglês

10.7554/elife.14552

2050-084X

Andrea Strakova, Máire Ní Leathlobhair, Guodong Wang, Tingting Yin, Ilona Airikkala‐Otter, Janice L. Allen, Karen M. Allum, Leontine Bansse-Issa, Jocelyn Bisson, Artemio Castillo Domracheva, Karina Ferreira de Castro, Anne M. Corrigan, Hugh R. Cran, Jane T. Crawford, Stephen M Cutter, Laura Keenan, Edward M. Donelan, Ibikunle A. Faramade, Erika Flores Reynoso, Eleni Fotopoulou, Skye N. Fruean, Fanny Gallardo-Arrieta, Olga Glebova, Rodrigo F. Häfelin Manrique, Joaquim Henriques, Natalia A. Ignatenko, Debbie Koenig, Marta Lanza‐Perea, Remo Lobetti, Adriana M. Lopez Quintana, Thibault Losfelt, Gabriele Marino, Iñigo Martincorena, José Simón Martínez-Castañeda, Mayra Fernanda Martínez-López, Michael J. Meyer, Berna Nakanwagi, Andrígo Barboza De Nardi, Winifred Neunzig, Sally J. Nixon, Marsden M Onsare, Antonio Ortega‐Pacheco, Maria C. Peleteiro, Ruth J. Pye, John F. Reece, Jose Rojas Gutierrez, Haleema Sadia, Sheila K. Schmeling, Olga Shamanova, Richard K Ssuna, Audrey E. Steenland-Smit, Alla Svitich, Ismail Thoya Ngoka, Bogdan Alexandru Vițălaru, Anna P. de Vos, J. P. de Vos, Oliver Walkinton, David C. Wedge, Alvaro Wehrle-Martinez, Mirjam G. van der Wel, Sophie A. E. Widdowson, Elizabeth P. Murchison,

Microbial infections and disease research

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.