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Genetic Study of Sled Dogs Traces Specific Haplotypes Related to Arctic Adaptation

NEW YORK – Through a genetic study of modern and ancient sled dogs, an international team of researchers has found that the major ancestry of modern sled dogs traces back to Siberia, where sled dog-specific haplotypes that potentially relate to Arctic adaptation were established 9,500 years ago.

Sled dogs are one of the most specialized groups of dogs but their origin and evolution hasn't been as well studied as those of other dog groups, the researchers noted in their study, which was published on Thursday in Science. They applied a genomic approach to investigate the spatiotemporal emergence of modern sled dogs by sequencing the genomes of 10 modern Greenland sled dogs, a 9,500-year-old Siberian dog that was thought to have been a sled dog because of associated archaeological evidence, and a Siberian wolf that was about 33,000 years old.

They analyzed their data alongside genomes from 114 geographically and genetically diverse canids using whole-genome pairwise distances, principal component analysis, TreeMix admixture graphs, and other data, and found that the ancient wolf appeared alongside wolves, and that the ancient sled dog was more closely related to modern dogs.

"We found noteworthy genetic similarity between the ancient dog and modern sled dogs," the authors wrote. "We detected gene flow from Pleistocene Siberian wolves, but not modern American wolves, to present-day sled dogs."

Specifically, Zhokhov (the ancient sled dog) was most similar to Greenland sled dogs, Alaskan malamutes, and Alaskan and Siberian huskies and American pre-European contact dogs (PCDs). Yana (the ancient wolf) was more closely related to a Pleistocene wolf from Taimyr Peninsula than to modern wolves, whereas Zhokhov represented a lineage that diverged from the ancestor of present-day sled dogs, the researchers said. This suggested genetic continuity in Arctic dog breeds for at least the past 9,500 years.

Further, they found an excess of allele sharing between Yana/Taimyr wolves and PCDs/Zhokhov-sled dogs, suggesting that an admixture occurred between Pleistocene wolves and the ancestors of PCDs, Zhokhov, and sled dogs.

As previous studies had demonstrated an association between canine transmissible venereal tumors (CTVTs) and sled dogs, especially PCDs, the researchers went on to evaluate the relationship among Zhokhov, two CTVT genomes, and dogs and wolves using phylogenetic analysis and other data. They placed the CTVT genomes closer to PCDs than to sled dogs or Zhokhov, suggesting that the basal dog lineage that led to PCDs occurred in Eurasia about 6,000 years ago, or that there were multiple introductions of PCD-like dogs to the Americas.

Further analyses found no significant gene flow between any sled dog (including Zhokhov) and modern American-Arctic wolf populations compared with the Eurasian wolf, suggesting that gene flow from modern wolves has not contributed to the sled dog gene pool within the past 9,500 years.

"These results imply that Greenland sled dogs have largely been kept isolated from contact with other dog breeds, and that their lineage traces more genomics ancestry to Zhokhov-like dogs relative to other dog breeds," the authors wrote. "Isolation of Greenland sled dogs was supported by inference of their historical effective population size, which showed that these dogs had a relatively stable population size until a severe bottleneck about 850 years ago. The timing of the bottleneck is consistent with the colonization of Greenland by Inuit, suggesting isolation in Greenland ever since."

To investigate further, the team focused on eight genomic regions that are highly differentiated in sled dogs and three regions where other dogs differ from sled dogs and wolves, analyzing two sets of genes: those in which Zhokhov carries the same haplotype as modern sled dogs and those involved in adaptation to different diets.

They found that TRPC4 was highly differentiated in sled dogs, and the putatively selected haplotype bore a marked similarity to Zhokhov. TRPC4 is a transient receptor potential (TRP) channel protein that plays an important role in vasorelaxation and lung microvascular permeability. It is also involved in a temperature sensitivity pathway, where it interacts with TRPV2, which is also highly differentiated in sled dogs and codes for temperature and potentially pain receptors.

The researchers also found that CACNA1A, a calcium channel subunit that plays an essential role in skeletal muscle contraction, was highly differentiated in the sled dogs. CACNA1A has been reported to be under positive selection in humans, specifically the Bajau sea nomads, where it is involved in hypoxia adaptation, indicating it plays a possible role in managing exercise-induced hypoxia in sled dogs.

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