Canine transmissible venereal tumor (CTVT), the oldest known somatic cell line, is a “living fossil” of the original host, transmitted from its tumor cells to other canids during the mating process. Since it was shown ten years ago that living cells from an ancient host could be transmitted among canids, the origin of CTVT has been studied continuously.
Recent comparison of the CTVT genetic data with a comprehensive canine reference panel argued that the CTVT founder (the original canine infected with CTVT) is the closest detectable lineage to pre-contact dogs (PCDs, from North America). However, this previous study may not take into account several potential biases in the genotyping methods for CTVT samples and the strategy for collecting loci, and the genetic ancestry of the CTVT founder is still unknown.
A team of scientists from the Kunming Institute of Zoology of the Chinese Academy of Sciences (KIZ, CAS) and the Institute of Vertebrate Paleontology and Paleoanthropology of CAS recently developed a tool, the transmissible tumor genotyper (ttgeno), to obtain per-site allelic copy number of the five CTVTs from four continents. The study was published in Cell Research.
By extracting the biallelic intersection of the genotype-monomophic single nucleotide polymorphisms (SNPs) and polymorphic SNPs from the high-quality reference panel including ancient and modern worldwide dogs and wild canids, scientists determined the genotype of the candidate CTVT founder.
Through mutational spectrum assessment, they showed that the mutation signatures at these loci are the same as the germline signatures of dogs, confirming that these loci in the CTVT lineage contain germline rather than somatic mutations.
The results of population genetic analyses further supported an origin related to PCDs in North America. Specifically, the CTVT founder clustered into the clade of PCDs separating from worldwide dogs, and this single clade then formed a clade with modern Arctic sled dog population.
Besides, this study confirmed that the founder must have possessed introgressed regions from another species related to North American coyotes and wolves in different tests of gene flow. It demonstrated the previous result that native American dogs have been mostly replaced by dogs introduced by Europeans, and the primary extant lineages possessed no native American components.
This study firstly developed a convenient pipeline to analyze transmissible tumor. More importantly, the CTVT’s genotype-monomorphic sites have been shared in the DogGD database from the iDog platform, which can be used not only to study the early stages of CTVT somatic evolution, but also as a “living fossil” to include in future studies on the evolution of dogs.
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