Digging Data

Just as humans developed crop plants and domesticated animals from wild ancestors, we also used artificial selection to create distinct varieties and breeds of these species. Domestic dogs evolved from ancient, now-extinct wolf ancestors tens of thousands of years ago^[1] – and then, over the last 200 years, humans further selected subsets of dogs, creating Great Danes, Chihuahuas, and the full gamut of more than 450 breeds.

During the process of developing different breeds, the focus was on traits. We didn’t know which genes bestowed, for example, swimming skills or rat-catching ability; we just knew that we wanted dogs that were better at pulling fishing nets (leading to Chesapeake Bay Retrievers and Portuguese Water Dogs) and clearing out pests (leading to the Rat Terrier). In recent decades, scientists have been able to track down some of the genes that we unwittingly selected for in different breeds.  Elaine Ostrander, a biologist at the National Institutes of Health, is one of these scientists. She and her team study dogs in order to answer basic questions about genetics that have implications for human health.

In one study, Elaine and a team that included Jaemin Kim, Falina Williams, Dayna Dreger, Jocelyn Plassais, Brian Davis, and Heidi Parker focused on sport hunting dogs, which are an active group of breeds that perform many different jobs.  This group includes spaniels, retrievers, and hunting dogs.  The team identified 59 genes that seem to have been the targets of recent selection in these dogs.^[2] A particular variant (i.e., an allele) of one of these genes – called ROBO1 – was common in the most agile breeds. These athletic breeds were unusually likely to have an A base at a location in the gene where other breeds were more likely to have a C base. The initial data suggested that ROBO1 was one of the genes that humans unwittingly affected when they artificially selected breeds for different sorts of athletic abilities, but the team wanted more evidence.

Background

Broadly, agility is the ability to move quickly and easily, but for dogs, it can have a more specific meaning.  Agility is a sport in which a person directs a dog to run through a complex obstacle course. For a dog to perform well in agility competitions, it must have both the athletic skills to make it through the course quickly and the mental skills to respond nimbly to commands and assess obstacles.

ROBO1 may be related to those mental skills. From studies of humans, we know that ROBO1 is involved with brain development. Different versions of ROBO1 affect how the brain works and learns. For example, having a certain version of ROBO1 seems to contribute to dyslexia, a condition where people have trouble reading.

Hypothesis

The team had identified the A version of ROBO1 based on a relatively small sample of breeds. This led to the hypothesis that the A version of the gene was favored by artificial selection in breeds in which humans desired traits that lead to high agility.  If this hypothesis were true across breeds, then we’d expect the A gene version to be more common in more agile breeds – that is, we’d expect to observe a positive relationship between the frequency of the A gene version and breed agility.

Data

To assess agility, the team used records of which breeds were entered in agility competitions and which breeds actually won agility titles. For each breed, they calculated the number of titles won per dog of that breed entered in competition. They then divided breeds into eight groups according to how likely each breed was to win agility titles:

Top performers (such as Border Collies and Pumis, both herding dogs) were in the red group. Breeds that never or very rarely won agility competitions (like the Greyhound and Anatolian Shepherd) were in the blue group.

To figure out how common the A gene version of ROBO1 was in these different groups of dogs, the team turned to a database of dog DNA sequences.  They found ROBO1 data for 1243 dogs of breeds in one of the eight breed groups.  These were not dogs that had necessarily competed in agility trials themselves; they were just dogs that were members of the same breeds as competitors.  For each of the eight breed groups, the team calculated how common the A gene version of ROBO1 was compared to other gene versions. Here is what they found:

On this graph, the x-axis orders the eight breed groups from least likely to win agility titles (far left) to most likely (far right).  The y-axis shows how common the A gene version is in that group. So, for example, a frequency of 0.4 means that the A gene version was found in 40% of the sequences from dogs of that group.  There is a clear, strong relationship between tendency to win agility titles and frequency of the A gene version: the regression line slopes upwards, and this is significant (p = 0.0038). R² indicates how well the frequency of different gene versions is explained by the breed group. An R² of 0 would indicate that breed group cannot predict the frequency of the A gene version at all.  An R² of 1 would indicate that one can precisely predict the frequency of the A gene version based on breed group. In this case, the R² value of 0.77 indicates that 77% of the variation in the frequency of the A gene version is explained by breed group. These findings further support the hypothesis that the A version of ROBO1 was under strong artificial selection by humans in breeds for which humans desired traits that lead to strong agility. Now researchers can build on this hypothesis to learn exactly how the A version of ROBO1 impacts dogs that carry it, why the A gene version was favored in some breeds but not others, and importantly, how this might be related to athletic performance and other traits in humans.

Stepping into science

When Elaine Ostrander learned about genetics as a sophomore in high school, she knew she’d found her calling. She wanted to be a scientist. But she didn’t have any role models around her: no parent or friends were scientists. So Elaine forged her own path. Throughout high school and college, she worked all sorts of jobs – tutor, waitress, janitor, dishwasher – so she could get the training she needed for her dream career. And she made it. Elaine now leads her own lab, where she helps train the next generation of scientists and builds new knowledge about genetics.