skip to primary navigationskip to content
 

Selfish mitochondria in a canine transmissible cancer

last modified Jun 16, 2020 03:35 PM

A new study by the Transmissible Cancer Group published in Nature Communications today!

Previous research 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 canine transmissible venereal tumour (CTVT) creates a unique opportunity to understand the competitive dynamics of two types of mtDNA juxtaposed within the same cell.

In a new study, published in Nature Communications today, we 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. We 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.

 

CTVT selfish mitochondria
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 team 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 us!

 

Article citation: Strakova, A. et al. Recurrent horizontal transfer identifies mitochondrial positive selection in a transmissible cancer. Nat Commun 11, 3059 (2020).

The article is featured in the Nature Communications Editors’ Highlights!

 

Interested further? See where this story began: