Infectious tumors steal host mitochondria in canines

What’s scarier than cancer? Infectious cancer? Dogs have been living with it for the last 10,000 years. In fact, canine transmissible venereal tumor, or CTVT, appears to have originated at roughly the same time that early canine domestication began. CTVT is considered a highly adapted cancer composed of asexually reproducing cells that are now believed to be genetically distinct from the host. These “cancer cells” essentially act as unicellular pathogens, invading a new host during copulation and reproducing to form nasty, though thankfully somewhat treatable, tumors.

Through extensive sequencing of the canine mitochondrial genome, evolutionary biologists have successfully constructed a high-resolution phylogeny of domestic dogs, tracing all extant clades back to the most recent common ancestor. To determine whether or not the CTVT disease was in fact genetically separate from its hosts,  15 host mitochondria were sequenced in conjunction with their tumor genome. In all cases, CTVT mitochondrial genes proved to be genetically unrelated to their host.

The twist in this study came when the researchers realized that CTVT mitochondrial genes are not only unrelated to their host, but differ dramatically from their own nuclear genes. How could a single cell contain a nucleus and mitochondria with seemingly unrelated genes?

It turns out that the unique biology of CTVT provides an opportunity for geneticists and evolutionary biologists to study an event that occurs quite rarely in nature- the transfer of genes between a complex multicellular eukaryote and a single celled organism. Horizontal gene transfer from pathogen to host is a relatively common phenomenom, but rarely does it operate the other direction, and examples of horizontal gene transfer from a complex eukaryote are particularly scarce. However, in the case of CTVT this phenomenom provides the best explanation for a number of puzzling aspects of the pathogen’s genome. The occasional transfer of canine mitochondria into CTVT cells explains the unusually high level of genetic variability within CTVT mitochondria, as well as the stark unrelatedness of mitochondrial and nuclear DNA.

This unusual transfer event, rather than being a randomly occuring, stochastic process, may in fact be keeping the CTVT cell line alive. CTVT cells have abnormally high metabolic rates, necessitating the production of lots of mitochondria. A high rate of mitochondrial division also means an increased number of deleterious mutations in the mitochondrial genome. When enough “bad mutations” accumulate, mitochondria lose the ability to function properly. Researchers are now suggesting that host mitochondria may be more “evolutionarily fit” than their pathogens’, and that occasional transfer events may in fact resuce CTVT mitochondrial function. The horizontal transfer of mitochondrial genes has been experimentally achieved in mammalian tissue cultures. This unique mechanism of replacing a broken genome with a perfectly functioning one from host cells is not outside the realm of possibility.

The only other known transmissible tumor, Devil facial tumor disease, occurs in Tasmanian devils.

Rebbeck et al. 2011.  Mitochondrial Capture by a Transmissible Cancer. Science. In press.

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