Mitochondrial genetic diversity, selection and recombination in a canine transmissible cancer.
Strakova A., Ní Leathlobhair M., Wang G-D., Yin T-T., Airikkala-Otter I., Allen JL., Allum KM., Bansse-Issa L., Bisson JL., Castillo Domracheva A., de Castro KF., Corrigan AM., Cran HR., Crawford JT., Cutter SM., Delgadillo Keenan L., Donelan EM., Faramade IA., Flores Reynoso E., Fotopoulou E., Fruean SN., Gallardo-Arrieta F., Glebova O., Häfelin Manrique RF., Henriques JJ., Ignatenko N., Koenig D., Lanza-Perea M., Lobetti R., Lopez Quintana AM., Losfelt T., Marino G., Martincorena I., Martínez Castañeda S., Martínez-López MF., Meyer M., Nakanwagi B., De Nardi AB., Neunzig W., Nixon SJ., Onsare MM., Ortega-Pacheco A., Peleteiro MC., Pye RJ., Reece JF., Rojas Gutierrez J., Sadia H., Schmeling SK., Shamanova O., Ssuna RK., Steenland-Smit AE., Svitich A., Thoya Ngoka I., Vițălaru BA., de Vos AP., de Vos JP., Walkinton O., Wedge DC., Wehrle-Martinez AS., van der Wel MG., Widdowson SA., Murchison EP.
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.