Tibetan Mastiffs Acquired High-Altitude Variants From Tibet Gray Wolf

NEW YORK (GenomeWeb) – By interbreeding with local gray wolves, Tibetan Mastiffs acquired gene variants that provided them with adaptations to a highland environment.

Tibetan Mastiffs adapted quickly to high altitudes over a short amount of time. They have, for instance, thicker coats and lower hemoglobin levels than low-altitude dogs. But how these adaptations arose has been unclear.

To trace their origin, researchers from the Shanghai Institutes for Biological Sciences compared the genomes of Tibetan Mastiffs to those from highland and lowland dogs and wolves. As they reported yesterday in Molecular Biology and Evolution, the researchers found that though Tibetan Mastiffs were more closely related to Chinese dogs, they harbored genomic hotspots under strong positive selection that include the EPAS1 and HBB loci that appeared to come from the Tibet gray wolf.

“[I]ntrogression was the most plausible explanation for the two loci in the highland dogs, which enabled them to adapt to the hypoxia environment in a relatively short time period,” Shanghai’s Yixue Li and his colleagues wrote in their paper.

Using the Dog Genome SNP Database, the researchers amassed raw SNP data from 29 canids from seven populations, including the high-altitude Tibetan Mastiffs, Tibet grey wolves, and Qinghai grey wolves; the low-altitude Xinjiang grey wolves, Inner Mongolia grey wolves, and Yingjiang indigenous dogs; and, as an outgroup, the golden jackal. Through this, Li and his colleagues uncovered some 18 million SNPs and 5 million indels among the 29 canids.

The researchers conducted a principal components analysis of these SNPs that separated the golden jackal from the dogs and wolves and separated the dogs, highland wolves, and lowland wolves. Deeper analysis separated all four wolf populations but kept the dog populations as a single cluster. A neighbor-joining tree similarly first split the dogs and wolves, and then split those populations by whether they lived at high or low altitudes. Together, the researchers said, this indicates that Tibetan Mastiffs are more similar to dogs than to wolves.

Li and his colleagues also examined admixture among these populations. While a population structure analysis and the ABBA/BABA test were unable to uncover evidence of admixture between high-altitude dogs and wolves, when the researchers performed the ABBA/BABA test on smaller genomic segments they did find evidence of introgression between Tibetan Mastiffs and Tibet gray wolves at local regions.

A number of these regions, they noted, coincided with previously reported regions with signals of selective sweeps in Tibetan Mastiffs. One of these regions includes the EPAS1 gene, which has a role in hypoxic responses. The researchers noted reduced sequence divergence between Tibetan Mastiffs and Tibetan wolves across the EPAS1 locus, as compared to the genomic background, also indicating there was introgression.

The researchers dated the introgression event at some 24,000 years ago. That corresponds, they noted, with the arrival of people on the Tibetan plateau.

Likewise, a locus on chromosome 21 that covers the HBB gene cluster, which is also involved in hypoxia response, appeared to be introgressed from wolves as well.

Overall, Li and his colleagues said their findings indicate that the ancestors of Tibetan Mastiffs mixed with Tibetan wolves, although most wolf-origin DNA was lost in the dogs during breeding except for ones that provided advantages for the highland living.

“These results indicated that by secondary contact with wild relatives, the adaptive introgression may be an effective and rapid way for domestication animals to adapt to the new environment,” the authors wrote in their paper.