Researchers unveil evolutionary effects on mammalian species due to extreme environments

LAWRENCE— Picture yourself on vacation, hiking up the steep side of a mountain trail. The sun is warm, the air thin and dry, and your sense of smell seems to be less sharp than normal.

For high-altitude mammals, that reduced sense of smell is typical, new research from the University of Kansas shows. Lead author Allie Graham, assistant professor and integrative biologist with the Department of Molecular Biosciences and Center for Genomics, has recently discovered that numerous high-altitude species, such as mountain goats or pika, have had a genetic shift toward olfactory receptors with limited functionality. 

Put more simply, through evolution, these animals have developed a worse sense of smell.

Graham and her fellow researchers looked at 17 high-altitude species’ genomes and more than 100 low-land species to compare them and see whether there was any correlation between animals that had been invading high-altitude locations and genes within their genomes becoming nonfunctional.

“I've been working on high-altitude research since 2012, while working toward my Ph.D. But it's always been through the lens of genes functioning optimally. As I've gone through my career, I’ve discovered certain elements of nonfunctionality that might actually be beneficial. This nonfunctionality might actually be useful in evolving tolerance to low oxygen at altitude,” Graham said.

Though Graham’s recently published paper in the journal Cell Biology, “Convergent reduction of olfactory genes and olfactory bulb size in mammalian species at altitude,” focuses on changes within olfactory receptors, Graham’s research did not begin that way.  

“When I started this particular project, olfactory receptors weren't even on the table. I was looking for patterns, and I had some thoughts about what might end up being potential lines of research, but I was letting the data speak for itself, and the only thing that came out as a significant correlation was the olfactory receptors,” she said.

“In this paper, I'm playing around with a thought experiment of, 'What are the possibilities?' For example, when hikers or mountaineers go up high, there is a loss of general smell because there's sinus inflammation. Hikers also experience low barometric pressure and aridity — it's very dry. Plus, the fact that odorants don't travel as far.

“The research paper shows it could be some combination of those effects. Either, being the inflammation and aridity, which causes the sense of smell to disappear over time, or because the way things smell or the landscape of smells at altitude is different or less important,” Graham said.

Loss of a sense is not uncommon evolutionarily, according to Graham. Often certain senses become less important than others, especially when an animal is living in an extreme environment like a cave system, deep ocean or at high altitude. Cavefish, or other cave-dwelling animals, for example, lost their sense of sight in exchange for developing better senses of smell or hearing.

“It could be that vision, or taste, or hearing, is more important for high-altitude animals. But that, again, is just a hypothesis, because we can't answer that with the data that we have. It opens up more questions,” Graham said, “In the future, I want to look at other types of analyses or do more counts that involve gustatory receptors, or vision-related studies with cone and rod genes, to see if they are actually under positive selection.”

For her current research, Graham uses large-scale genomic data that she has generated from her own experiments but also the wealth of available sequence data in public repositories like NCBI. Future research is likely to use facilities at the KU Natural History Museum and the Micro CT facilities at the Lawrence campus. 

By taking measurements using endocranial casts, Graham will be able to look at different measurements, like ocular shape or the curve of an ear canal and compare them across species to see if other senses are compensating for a lack of smell in high-altitude animals.

This chance to continue research is a thrilling possibility for Graham, who said, “Something philosophical for me that results from this paper is that when you're coming up as a scientist and you're taking classes and hearing people talk about science inadvertently, it kind of feels like, ‘Oh, well, I'm coming too late into the game on this, everything that there is to know about it has already been found.’

“I don't know if that’s naivete, but that’s what I remember feeling. ... There's been a couple of times both as a grad student, and in my postdoctoral work, where I found an interesting pattern nobody had found before and it seemed very big and obvious, and it completely changed how I thought. Changed how the field potentially thinks about that particular thing, and it opens up all these new questions that nobody was thinking about prior to that particular result.

“At the beginning starting a career in research, it feels like there's only one pie and you're trying to fight for a tiny slice, but in reality, there are multiple pies. You just don't see those pies yet, you're focused on the one pie, and then you realize there's a whole buffet that nobody's touched. All the possibilities make me feel excited about continuing science.”