SALT LAKE CITY — In the midst of your post-Thanksgiving-feast stupor this holiday, you might find yourself asking: How do hibernating animals simply sleep off the weight they pack on pre-slumber?
University of Utah researchers asked that question in a study published recently in the academic journal Cell Reports. The findings, they say, could potentially lead to interventions and treatments for obesity and metabolic disease.
“Many different species in the world have evolved these extraordinary superpowers that can help us learn about the mechanisms that are causing diseases in humans, and potentially prevent those diseases,” said Christopher Gregg, associate professor in the Department of Neurology & Anatomy.
“And the ability to sequence and analyze genomes has really revolutionized our ability to uncover these secrets underlying these superpowers, or the mechanisms that evolved. So it’s an exciting time when we can start bringing together human biology and the biology of all these extraordinary animals to learn a lot about each other,” he said.
In the project that began a few years ago, researchers analyzed full genome sequences from small hibernating mammals — the thirteen-lined ground squirrel, little brown bat, gray mouse lemur, and lesser Madagascar hedgehog tenrec.
They also analyzed genomes from humans and non-hibernating animals.
After collecting the “huge” data set of genome sequences that had been shared from researchers around the world, the researchers built software and data analysis tools to compare the genomes. They were looking for parts of the genome that belong to every mammal, including humans. Those shared parts are called “conserved regions.” After eliminating all the parts that aren’t shared, only 5% of the genome remains to examine, Gregg said.
In the four hibernating species, the researchers found that they each had areas of “changed elements” that modified the sequence of their DNA — the changed areas were called “parallel accelerated regions.” Parallel accelerated regions are mechanisms that have evolved independently at an accelerated pace — they’re called “parallel” because they are shared among the four species.
After discovering the parallel accelerated regions, the researchers set out to learn what the regions were and what their function was. Most of the regions aren’t actually genes, Gregg said, but instead are “switches that control when the genes turn on and turn off,” or regulatory elements, that allow them to hibernate.
The “switches” were disproportionately located near genes linked to obesity in humans in the past, Gregg said.
That insight revealed how hibernation evolved, and the potential mechanisms involved in shaping obesity and metabolic traits in humans, according to Gregg.
“It might not be that the genes themselves, alone, are the critical part. It’s the switches that are turning the genes on and off in different ways that are the critical part. So now we have an understanding of the identity of those switches.”
He said the researchers now hope to discover if people who become obese “have changed how these elements work,” or if they have a mutation in those elements.
“And that’s kind of what this study opens up. It’s a big new frontier to better understand obesity, because we now have understanding of the important switches that might be involved,” he said.
If the switches turn out to play a role in the obesity in humans, the information could help doctors identify those at risk for developing obesity and metabolic disease early and tailor a lifestyle that prevents it. Another possible application — if the switches are proven to play an important role in human obesity — would be to learn how the switches work in people, and then develop therapeutics that counteract effects, Gregg said.
Gregg’s lab is now pursuing those questions, and based on what they discover, could later move on to clinical research.
“We’re really excited about it. And the people in the lab are really excited about it, there’s people that want to come to the University of Utah to work on this,” he explained.
Though the genome sequencing technology that made the research possible has been available within the past 10 years or so, Gregg said it’s become more affordable in the past few years. That has allowed for the availability of more and more genomes to be shared worldwide.
This new study wouldn’t have been possible before 2016, he said, because there wasn’t enough information up until that point.
“We’re continuing, as a community, to sequence the genomes of other species, tens of thousands of species all around the globe. And then researchers share that information, they share the sequence information with each other, and we’re able to do studies on that shared genome data,” he said.
The study built upon a previous U. study that looked at animals that had developed “biomedical superpowers,” including elephants, which evolved the ability to evade cancer, and dolphins that evolved ways to avoid blood clots.
