A deep dive connects canine genetics, brain physiology and behavior to explain why collies are different from terriers

A deep dive connects canine genetics, brain physiology and behavior to explain why collies are different from terriers

From the energetic Border Collie to the friendly Golden Retriever, there are over 350 dog breeds today, each with specific physical and behavioral traits. Although previous research into dog genomes has revealed the genetic basis for variations in body size and shape between breeds, the genetic basis for complex behaviors – hunting, herding, guarding, pointing, drawing, etc. – was a difficult challenge to solve.

Today, researchers at the National Human Genome Research Institute (NHGRI) have found that the ancestry relationships of about eight major canine lines correspond to distinctive behaviors. As a result, investigators were able to identify the underlying genetic basis for these behaviors. A major finding was that many genes involved in axon guidance, which determines how neurons connect to each other in the brain, had been altered in several lineages, and this was particularly the case in the dog lineage. of shepherd. Because genes that influence brain development and behavior in dogs are likely to do the same in humans, identifying genetic variation in locations in the human genome corresponding to behavior-related regions in the dog genome dog could lead to new knowledge on the genetic basis. human behaviors and psychiatric conditions, say the researchers.

“This article brings behavior back to the forefront when we think about the impact of selection on the evolution of dog breeds,” says Evan Maclean, director of the Arizona Canine Cognition Center at the University of Arizona, who did not participate in the study. “While it’s true that we did a lot of selection for aesthetic traits, this work clearly shows that much of the genetic action is in pathways related to the brain (and therefore presumably related to behavior and cognition).”

The Dog Genome Project, which began in the early 1990s, has allowed researchers to map genes for diseases, as well as genes for characteristics such as height, leg length and body shape. But “the truth is that the real motivation behind the Dog Genome Project has always been to find genes for behavior,” says Elaine Ostrander, who leads the project at NHGRI and is the lead author of the new study. Breeds have a variety of stereotypical behaviors, but identifying the genes behind these behaviors has proven extremely difficult so far, she explains.

To tackle the challenge, Emily Dutrow, a postdoctoral fellow in Ostrander’s lab at NHGRI and lead author of the new study, used methods inspired by single-cell sequencing, a now widely deployed technique for sequencing RNA instructions, or transcripts. , from individual cells to derive an understanding of the function and relationship of different cell types in the body. Instead of applying the method to a set of cellular transcripts, a transcriptome, she applied it to dog genomes to identify the ancestry relationships of dog breeds. Using genomic data from over 4,000 dogs (samples have been shared with the Dog Genome Project by dog ​​owners around the world), “I was able to establish these age-old relationships between all dog breeds that exist. on Earth,” Dutrow said. .

By first identifying these ancestry groups, or lineages, researchers could then look for evolutionary changes along each. And because the lines classified themselves neatly into eight behavioral groups, it became possible to identify which parts of the genome differentiate a sheepdog from a guard dog, for example. To do this, the researchers linked their genomic analysis to behavioral data from a survey of more than 40,000 dogs conducted about 15 years ago at the University of Pennsylvania School of Veterinary Medicine.

“This article uses a new framework to think about race relations,” says Gitanjali Gnanadesikan, who holds a doctorate. candidate at the Arizona Canine Cognition Center, which did not participate in the study. “In evolutionary biology, we tend to think of relationships between species or lineages as branching trees. And while that has its place, dog breeds are especially complicated because they’re not separate species, and there’s a lot of interbreeding, especially at the time of breed formation. This new framework is able to take these complex relationships and both visualize and quantify them in a way that allows for new analyses, which is exciting.

Bridgett vonHoldt, a genomics who studies canine ancestry at Princeton University and was also not involved in the work, agrees. This new approach, which she calls “incredibly elegant” and “impressive”, has allowed researchers to include not only purebred dogs but also mixed-breed dogs in their investigation of underlying genetic behaviors. She described the work as “a historical study” for the field.

The researchers’ analysis revealed eight main trajectories of what vonHoldt calls “dogdom”: terriers, sled dogs, sheep and cattle dogs, greyhounds, spitz and “primitive type” dogs, pointers, dogs stoppers and retrievers.

The team found that whole suites of genes were involved in the evolution of specific behaviors in the different dogdom lines. This contrasts with traits such as body size and coat color, which are only regulated by a few genes. “The behavior is just much more complex,” says Ostrander. “So it’s going to involve more of the genome.” The researchers also determined that most of the genetic variants implicated in behavior were found in regions with genes that turn other genes on or off rather than in coding regions that provide instructions for making proteins. This means that it is particularly important to modify when and where coding genes are activated early in life. “You basically need all these genes. It’s just that you want to tweak or tweak them to get those nuanced behavioral changes,” says Ostrander.

The researchers examined where and when genetic variants associated with particular lineages were activated during development, and they found that many of them were activated during brain formation. More importantly, many genetic variants associated with the sheepdog lineage were involved in axon guidance, which is the process by which neurons connect to each other.

“For me, it was incredibly striking,” says Ostrander. “I certainly didn’t expect that. I thought it would be genes from all over the nervous system doing all kinds of different things. I didn’t expect one pathway to be so incredibly important in the performing those behaviors. For example, the changes might have involved the number of cells in a certain part of the brain or the proportions of different cell types.” But really, it’s really how different parts of the brain talk to each other. that’s most important” in determining these behaviors, Dutrow explains.

The researchers found that much of the brain and behavioral variation in the Eight Dogmas is related to motivation and learning. For example, says Dutrow, hunting dogs need to be self-directed learners who can follow their noses rather than being influenced by human direction. But hunting dogs, which help their handlers find and retrieve game, must be in close sync with their human handlers, she adds.

However, the genetic variants associated with these lineages were not exclusively involved in brain and behavioral regulation. For example, in hunting dogs, most genetic variants were associated with the muscular system, the researchers determined.

Another important finding was that most of the genetic variants identified by the team were already present in wolves. “It goes back to the idea that the basic ingredients for all the variations we have in dogs today were largely present in an ancestor of the wolf,” says Maclean. But the changes from the ancestor of the wolf were different in different lines of dogs. “It’s interesting to me because it really emphasizes the diversity of dogs and how evolution has progressed in different directions in these lines, both through selection and [random] genetic drift,” says Gnanadesikan.

This study provides the basis for more detailed research into each line of dogs and what makes that line unique. Additionally, Ostrander hopes to take the behavior-related genetic variants that are different across canine lines and examine the variation in corresponding regions of the human genome. It’s likely that genes that affect dog behavior also impact human behavior, she says. Because dog breeds have stereotypical behaviors and not as much genetic variation as humans, it’s “a much better starting point to understand what some of these regulatory regions really do,” Ostrander adds. Ultimately, these comparative studies could lead to new insights into human behaviors, including those associated with neuropsychiatric disorders, she suggests.

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