Scientist’s Best Friend: Princeton professor Bridgett vonHoldt, with Marla, is studying how DNA can reveal social behavior traits in dogs. VonHoldt (but not Marla) participates in the Prince­ton Innovation event November 8.

Every day researchers at Princeton University make discoveries that push the frontiers of science forward. But except for avid readers of scientific journals, the average member of the public has little idea what exactly is going on there. On Thursday, November 8, the university offers the public a chance to see the fascinating work taking place in the university’s research labs.

The Celebrate Princeton Innovation event, online at invention.princeton.edu, is a website and video series that highlights this research. The event will be 5 to 8 p.m. at the Frick Chemistry Lab atrium, where a selection of researchers will discuss their work.

One of them, assistant professor Bridgett vonHoldt in the ecology and evolutionary biology department, has more reason than most to reach out to the public. She has enlisted the public in her ongoing work, which probes the nature of the relationship between humans and dogs.

VonHoldt’s research group is studying the link between a handful of gene mutations found in dogs that make them friendly to humans. Her research indicates that without these genetic changes, dogs would be no more inclined to curl up at your feet than wolves are.

What’s more, she found, human beings may have an analogous set of genes related to sociability. In a study published in 2017, an interdisciplinary team led by vonHoldt sequenced part of the domesticated dog chromosome and found DNA that was associated with social behavior. In particular, the researchers found that one set of genes called the Williams-Beuren Syndrome Critical Region was highly linked to dogs’ tendency to seek physical contact, help, and communication from humans.

‘Dogs are a biomedical model for humans disease because it is known they share many conditions. As such, understanding genetics in either one can inform us about the other.’

The human genome has a counterpart to this region in the canine genome. Certain mutations in this region in humans cause them to become overly gregarious and engage in other hyper-social behaviors.

The 2017 study was a followup to a dissertation paper that vonHoldt published in 2010 in which she identified the dog version of the WBSCR genes.

“My dissertation research identified a number of genomic regions associated with positive selection in the domestic dog relative to gray wolves,” vonHoldt says. “Statistical ranking of them led to the second position being a single nucleotide polymorphism (SNP) near a gene known to be involved in Williams Beuren Syndrome. The characteristics of the syndrome were strikingly similar to those of domestic dogs.”

For the most recent paper, vonHoldt’s colleague, Monique Udell, an assistant professor of animal and rangeland sciences at Oregon State University, studied 18 domesticated dogs and 10 captive wolves and took DNA samples from them.

She put the dogs and wolves through a series of tests designed to measure their affinity for socializing with humans. For example, a sausage was placed in a “puzzle box” that required the canines to pull on a rope to get it. The more sociable animals looked to the humans for assistance.

The study showed that the wolves, which lacked many of the specific genetic mutations, sought little help from humans, while domestic dogs, which had the mutations, spent more time looking to humans for help solving the puzzle.

Since making this discovery, vonHoldt has built on this finding to create a genetic test that measures how many of the hypersociability mutations an individual dog has. That test could be used, for example, by animal shelters to determine which dogs might be most suitable for adoption. “I have never thought about commercial products for my research before,” she says.

A Princeton University press release about her work suggests some commercial applications: “Genetic testing could also give trainers and breeders a way to determine an animal’s social tendencies. The test may make it possible to determine at an early stage whether a dog is suitable to become a service or guide dog. The test, which requires collecting a cheek swab, could be added to existing genetic test kits marketed to dog owners.”

Beyond these practical applications, vonHoldt’s work could help answer one of the oldest questions about the nature of the relationship between humans and dogs. How, exactly, did wild wolves evolve into the lapdogs and companions we know today? Scientists have tended to assume that at some point, humans took in wolf puppies that approached their camps, and bred together the ones that were the most trainable, and over time, turned them into hunting companions.

‘My work is still constantly evolving and uncovering new numerous questions that need to be addressed. One insight creates a dozen questions.’

VonHoldt’s research changes this story slightly: at least one expert, after reading her study, said it now seems more likely that the original dog breeders selected the friendliest dogs; the ones that had this particular mutation, rather than the ones that were quickest on the uptake.

“The study is exciting because it provides such strong support for the ‘survival of the friendliest’” hypothesis of dog domestication, Brian Hare, an evolutionary anthropologist at Duke University who was not involved in the work, told Science Magazine. “In ancient wolves with these gene disruptions fear was replaced by friendliness, and a new social partner was created.”

VonHoldt says there is still much work to be done on this question. “Canine geneticists still do not agree about the timing and location of dog domestication,” she says. “Though this is not the goal of my own research, it is something that the community continues to work towards understanding.”

Her work has implications beyond just dogs. It’s possible that similar mutations in other species could result in animals that are very friendly, just like dogs.

“My finding is suggestive that some genes, when mutated or abnormal, could produce similar results in maybe all mammals, or all vertebrates, etc.,” vonHoldt says. “Some genes are conserved in their functions and no matter in which taxon they are mutated, they could produce a similar response. I’m unsure if my gene of interest is that such gene. Dogs are a biomedical model for humans disease because it is known they share many conditions. As such, understanding genetics in either one can inform us about the other.”

VonHoldt has been pursuing this work in between her other duties as an assistant professor. Essentially, she has been working on a shoestring budget. Therefore she has turned to the public both for funding and for direct help in the research. She has used the science crowdfunding website www.experiment.com to raise $4,510 for her dog domestication studies.

“I find a consistently positive response when thinking about canine research, but the overall motivation to support scientific research is difficult,” she says. “Our current political administration has cut funding to research and science and the environment, etc. Many people are turning to crowdfunding. It can be successful but when our government does not support science, that message percolates throughout the nation that science is not a priority. Thus all types of funding are increasingly challenging.”

She is also reaching out to the public through her official university website at vonholdt.princeton.edu to ask the public to gather data on their own pet dogs. Through her site, she asks dog owners to fill out a survey asking about their dogs’ behavior, and then send in videos of the dog interacting with humans under carefully controlled circumstances. Would-be contributors who go through these steps are then sent a kit to take a cheek-swab DNA sample of their furry friends.

“I have had several hundred samples donated to me from the community, public, colleagues, and friends,” she says. “I have sent several hundred more sample kits out, with many never to be returned to me. People love the idea of helping a scientific study but that does not always translate into action.”

The daughter of an Air Force father and a mother who worked as a teacher, social worker, vet tech, and business owner, vanHoldt moved around a lot as a kid. She studied psychology as an undergraduate at Eckerd College, and earned a master’s in biology from NYU. When she joined the PhD lab of Robert Wayne at UCLA, she studied the genetics of gray wolves of the Rocky Mountains. “That soon expanded to evolutionary questions about domestication and genomic changes that occurred as a result of intense selection. My current lab works on various taxa, from plants to microbes to birds to caribou and of course canines,” she says.

She never had a dog until she and her husband got their Old English Sheepdog, Marla, who has been sequenced and genotyped many times. Despite her long years of research on dogs, it wasn’t any lab result but the experience of having one as a pet that altered vonHoldt’s thinking about them.

“I’m a cat person and have always had cats,” she says. “Marla is my first dog. Having her makes me think more about the foundation of that bond and how it is established and maintained. Our current relationship with dogs has evolved immensely since their domestication began thousands of years ago. That is a complex process that involves humans altering breeds for our own desired pets, and the dog genomes being plastic enough that we could shape it.”

VonHoldt says she is amazed by certain aspects of canine genetics.

“I marvel at (this may sound silly) the fact that people can know pretty close to exactly what a litter of purebred dogs will be like (e.g. looks, personality, disease risk, etc.),” she says. “I am typically obsessed with variation and understanding how it is a treasure trove for adaptation and evolution. I spend more time thinking about hybrids and admixture and how when two distinctly different entities reproduce, what do we know about their offspring? What can we predict? It’s almost nothing! But for dogs, I’m amazed at how most labs or beagles or bloodhounds are exactly what the breed advertises them to be. That high level of repeatability is amazing. Environment is certainly crucial for influencing many aspects of an individual. However, for dogs and their overall lack of intra-breed variation, I find this fascinating.”

Although vonHoldt has made several important discoveries, much work remains to be done, and it’s not going to happen without money.

“Science needs funding,” she says. “My work is still constantly evolving and uncovering new numerous questions that need to be addressed. One insight creates a dozen questions. We are a long ways from knowing the inner workings of what shapes canine traits, let alone behaviors.”

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