When humans started to domesticate dogs around 14,000 years ago, they unknowingly embarked on a genetics experiment that is still going on today. Although domesticated canines were probably first kept around the home because they made good watchdogs, humans have selected breeds in the past few hundred years to have an encyclopedia of exaggerated traits, from flat faces to stubby legs or wrinkly skin.

To hunt for the genes responsible for the blatant physical differences between, say, a dachshund and a shar-pei, researchers performed the first genome-wide analysis of 10 purebreds. They looked for mutations that were specific to certain breeds, suggesting that they might be responsible for a breed's distinct look. The study, which was published January 11 in Proceedings of the National Academy of Sciences, allowed the researchers to identify a gene linked to curly coats in poodles and another gene associated with wrinkles in shar-peis.

"As geneticists, the thing that we find most interesting is phenotypic variation, so outward appearance," says Joshua Akey, an evolutionary biologist at the University of Washington in Seattle and one of the lead authors on the study. "Dogs are probably the most phenotypically diverse organisms that exist."

Although humans have been able to create a cornucopia of canine varieties without knowing the genes behind the breeds, understanding genetic variations could shed light on diseases in humans that cause parallel physical changes. Akey says one example of such a morphological similarity is a rare human disease that causes the skin to thicken and fold. The mutations that have been attributed to this disease in people lie in the same gene that bestows shar-peis with their wrinkles.

Akey, whose research focuses on understanding natural selection, began working on artificial selection, or breeding, of dogs when he got a call from Mark Neff, a dog geneticist at the University of California, Davis. Neff had gathered genomic information from 275 dogs representing 10 breeds. For each dog, Neff had determined the sequence of nucleotides at 21,000 positions that are known to vary between breeds.

Akey, Neff and their colleagues used similar types of statistical methods for detecting mutations that arose during through natural selection to find which mutations emerged as a result of dog breeding. The researchers identified 155 regions of the genomes, containing 1,630 predicted genes, which show signs of selection. In the case of the shar-pei, Akey says it was easy to finger the gene responsible for their wrinkles because the region had a signature of selection shared among all of the wrinkly shar-peis, which is not found in any of the nonwrinkly sharpies, and contained only three genes. One of those genes had already been associated with the rare skin disease in humans.

In addition to the variations that appear to affect physical traits, the researchers also stumbled upon mutations that lie within genes that express proteins involved in the immune system. "That's what you typically see when you do these studies in natural populations [rather than artificially selected populations], so that was a little bit surprising," Akey says. He adds that selection for genes that improve immune function probably occurred even during breeding because of the strong selection for protection against diseases.

Next up, Akey plans to look for variations that could account for diverse dog behaviors, such as why pointers point and retrievers retrieve. Scientists have already gleaned insight into narcolepsy through studies with dogs. Like physical traits, humans have bred dogs to serve different functions, from herding to hunting. As such, a plethora of canine behaviors have arisen that, like physical traits, could share similarities with human traits.

Image courtesy of iStockphoto/grase