The domestication of dogs from gray wolves several thousand years ago required at least one or two severe population bottlenecks. But in the last 300 years, isolating modern dog breeds involved additional population bottlenecks, intense artificial selection for desired traits, and the inevitable inbreeding. Certain “fancy breeds” have well-known conditions, but researchers were still unsure about the specific effects of the accumulation of potentially harmful genetic changes in dog genomes.
Now, an analysis of the genomes of nearly a hundred members of the dog family reveal that taming man’s best friend unwittingly increased the number of harmful genetic changes. The findings were published in Proceedings of the National Academy of Sciences this week.
To study the patterns of deleterious genetic variation, UCLA’s Kirk Lohmueller and colleagues analyzed the complete genome sequences of 19 wolves, 25 village dogs (descended from indigenous dogs of no particular breed), 46 domesticated dogs representing 34 breeds, and also one golden jackal.
They found that through domestication, humans inadvertently increased the frequency of deleterious genetic variation in dogs compared with gray wolves: The average dog has 2 to 3 percent more derived deleterious copies of genes than the average wolf. This is a pattern driven by inefficient natural selection because of bottlenecks tied to domestication and breeding, not recent inbreeding.
Furthermore, these deleterious variants of genes were enriched in regions of the genome that are targeted by what’s called selective sweeps, a sign of positive natural selection. That means that those variants piggybacked onto positively selected genome regions. These areas were also enriched in disease-related genes.
Natural selection typically works to remove potentially deleterious variation associated with genes that are responsible for breed-specific traits. However, selecting for black coats in poodles, for example, caused a high frequency of KITLG gene variants, resulting in a higher chance of a skin cancer called squamous cell carcinoma in their nail beds.
Breeding small populations of dogs led to a buildup of harmful genetic variation, and for animals in general, large populations will be needed to conserve rare or endangered species.