Submitted by Lorraine Leonard on Wed, 17/06/2020 - 15:08
Selfish mitochondria in a canine transmissible cancer
The canine transmissible venereal tumour (CTVT) is an extraordinary type of cancer - it is infectious and transmitted between individual dogs by the direct transfer of living cancer cells themselves. The disease is primarily passed on during mating and leads to formation of genital tumours in both male and female dogs. This unusual cancer arose from the cells of one individual dog living around 8,000 years ago, and remarkably survived long beyond the death of that original host dog by spreading to other individuals. CTVT has since spread to all corners of the world, hopping from one dog to another. Previous research [AS1] has shown that at several points in history, mitochondria - which are compartments providing cells with their energy - from unrelated host dogs have been captured by CTVT, perhaps to aid survival of this long-lived cancer lineage.
The capture of mitochondrial DNA (mtDNA) by CTVT creates a unique opportunity to understand the competitive dynamics of two types of mtDNA juxtaposed within the same cell. In a new study, [AS2] published in Nature Communications on 16th June, the authors show that one particular type of mtDNA - named A1d1a - has been recurrently captured by CTVT cancer cells on eleven independent occasions. A1d1a is highly over-represented for CTVT mitochondrial capture compared with its frequency in the dog population. Genetic analysis of this mitochondrial type revealed the presence of an insertion at position 16660 of the mtDNA, which appears to reduce transcription - or the reading - of the mtDNA. The authors propose that A1d1a mitochondria unexpectedly win the race through a ‘selfish’ replicative advantage - by replicating more efficiently - rather than by providing a functional advantage. Apart from providing insights into the characteristics enabling the spread of this cancer that has ‘metastasised’ on a global scale, this work is of much broader importance, as understanding the competitive dynamics of mtDNA is crucial for advancing knowledge of mtDNA genetic disease and assessing the risks of therapeutic mtDNA transplantation in human embryos.
A model explaining repeated CTVT capture of the A1d1a mitochondria.
(1) Different types of mitochondria are captured by CTVT cells, (2) but A1d1a mitochondria have a specific insertion at position 16660 of the mtDNA, (3) causing reduction in transcription – or the reading of – the mtDNA in A1d1a, (4) suggesting that A1d1a wins the competition through a replicative (rather than functional) advantage.
This work was carried out at the Transmissible Cancer Group, Department of Veterinary Medicine, University of Cambridge. Thanks to veterinary collaborators from across the globe, the authors collected and analysed 539 CTVT tumours from 43 countries in this study. If you would be interested to participate in future studies carried out by the Transmissible Cancer Group as a collaborator through collecting CTVT samples, or if you have any further questions, please, do not hesitate to contact the authors: www.tcg.vet.cam.ac.uk.
Article citation: Strakova, A. et al. Recurrent horizontal transfer identifies mitochondrial positive selection in a transmissible cancer[AS3] . Nat Commun 11, 3059 (2020).
The article is featured in a Nature Communications Editors’ Highlights page.
Interested further? See where this story began:
Please, embed the following video (Canine transmissible venereal tumour: the contagious cancer that conquered the world): https://www.youtube.com/watch?v=CV9xGi8-p0o (this is a YouTube link, please, embed directly in the website using the share button).