Presenter Andrea Strakova
Authors Andrea Strakova (1), Adrian Baez-Ortega (1,2), Thomas J. Nicholls (3,4), Máire Ní Leathlobhair (1), Kevin Gori (1), Jinhong Wang (1), Patrick F. Chinnery (5), Maria Falkenberg (3), Claes M. Gustafsson (3), Elizabeth P. Murchison (1)
Affiliations 1. Transmissible Cancer Group, Department of Veterinary Medicine, University of Cambridge, Cambridge, UK 2. Bivalve Transmissible Neoplasia Group, Department of Zoology, University of Cambridge, UK 3. Department of Medical Biochemistry and Cell Biology, University of Gothenburg, Gothenburg, Sweden 4. Wellcome Centre for Mitochondrial Research, Newcastle University, Newcastle Upon Tyne, UK 5. MRC-Mitochondrial Biology Unit & Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK
Presentation Type Talk
Abstract
One unusual but particularly valuable natural model for studying mitochondrial DNA (mtDNA) dynamics is the canine transmissible venereal tumour (CTVT). CTVT is a contagious cancer affecting dogs, which spreads by the transfer of living cancer cells during mating, causing genital tumours. Although the CTVT nuclear genome is clonal and represents the DNA of the founder dog that lived several thousand years ago, CTVT mtDNAs are polyclonal and were acquired periodically by horizontal transfer from transient hosts. Capture of mtDNAs by CTVT cells results in a natural competition assay, whereby the relative fitness of diverse pairs of canine mtDNA haplotypes is assessed in vivo. We aimed to characterise mtDNA horizontal transfer dynamics within the CTVT population. We used low coverage whole genome DNA sequencing to survey mtDNAs in over one thousand CTVT tumours and matched hosts. The genetic analysis highlighted a single canine mtDNA haplotype, which has repeatedly colonised CTVT cells due to ‘selfish’ positive selection. Although CTVT is considered a biological oddity, its periodic uptake and juxtaposition of mitochondrial haplotypes provide broad and unexpected insights into mammalian mitochondrial dynamics.