Origins and evolution of a transmissible cancer.
Canine transmissible venereal tumor (CTVT) is an infectious disease of dogs. Remarkably, the infectious agent is the cancerous cell itself. To investigate its origin and spread, we collected 37 tumor samples from four continents and determined their evolutionary relationships using microsatellite length differences and microarray-based comparative genomic hybridization (aCGH). The different tumors show very little microsatellite variation, and the pattern of variation that does exist is consistent with a purely asexual mode of transmission. Approximately one quarter of the loci scored by aCGH show copy number variation relative to normal dogs, again with little variation among different tumor samples. Sequence analysis of the RPPH1 gene indicates an origin from either dogs or wolves, and microsatellite analysis indicates that the tumor is more than 6000 years old, and perhaps originated when dogs were first domesticated. By contrast, the common ancestor of extant tumors lived within the last few hundred years, long after the first tumor. The genetic and genomic patterns we observe are typical of those expected of asexual pathogens, and the extended time since first origin may explain the many remarkable adaptations that have enabled this mammalian cell lineage to live as a unicellular pathogen.
Rebbeck
Clare A
CA
Department of Biology, Imperial College London, Berks., United Kingdom.
Thomas
Rachael
R
Breen
Matthew
M
Leroi
Armand M
AM
Burt
Austin
A
D000818:Animals; D005075:Biological Evolution; D055028:Comparative Genomic Hybridization / Q000379:methods; D004283:Dog Diseases / Q000235:genetics*; D004285:Dogs / Q000145:classification / Q000235:genetics*; D018628:Gene Dosage; D005838:Genotype; D046228:Microarray Analysis; D018895:Microsatellite Repeats / Q000235:genetics; D009369:Neoplasms / Q000235:genetics / Q000662:veterinary; D010802:Phylogeny; D014685:Venereal Tumors, Veterinary / Q000235:genetics*; D019596:Wolves / Q000235:genetics