Tumor Genome as “Living Fossil” Reveals Ancient Introgression from Coyotes to Pre-contact Dogs in North America
2019-07-12 | | 【Print】

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, Chinese Academy of Sciences (KIZ, CAS) and the Institute of Vertebrate Paleontology and Paleoanthropology of the Chinese Academy of Sciences (IVPP, CAS) recently developed a tool, the transmissible tumor genotyper (ttgeno), to obtain per-site allelic copy number of the five CTVTs from four continents.  

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, they 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.  

Then, 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. This work also 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. Meanwhile, the work demonstrated the previous result of native American dogs have been mostly replaced by dogs introduced by Europeans, and the primary extant lineages possessed no native American components. 


This work 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.


This work was published in Cell Research under the title “Canine transmissible venereal tumor genome reveals ancient introgression from coyotes to pre-contact dogs in North America” (https://doi.org/10.1038/s41422-019-0183-2). Dr. WANG Xuan and Mr. ZHOU Bowen (from KIZ, CAS), Dr. YANG Melinda A. (from IVPP) are the co-first authors. Prof. ZHANG Yaping and Prof. WANG Guodong  (Professor at KIZ, CAS), Prof. FU Qiaomei (Professor at IVPP, CAS) are the co-corresponding authors. This work was supported by the Strategic Priority Research Program (B) of the CAS, the National Natural Science Foundation of China, the Animal Branch of the Germplasm Bank of Wild Species, CAS (the Large Research Infrastructure Funding), the Howard Hughes Medical Institute and the Youth Innovation Promotion Association, CAS.


+86 871 65199125cceaeg@mail.kiz.ac.cn
Chinese Academy of Sciences(CAS) Kunming Institute of Zoology, CAS Institute of Zoology (IOZ), CAS Shanghai Institute for Biological Sciences, CAS Academy of Mathematics and Systems Science, CAS
Institute of Genetics And Developmental Biology,CAS Institute of Hydrobiology,CAS Beijing Institute of Genomics, CAS Beijing Institute of Life Sciences,CAS Insititue of Vetebrate Plaeontology and Paleanthopolgy,CAS
Chengdu Institute of Biology, CAS Xi'an Branch, CAS University of Science and Technology of China