Fox Research Studies Cancer Susceptibility in Threatened Wildlife Populations
December 20, 2022A Catalina Island fox, Tyler Dvorak
Conservation research happens around the world as environmental changes continue to affect wildlife populations. One such change is the presence of naturally occurring cancers which threaten the health and genetic diversity of these populations. This is no exception for small and threatened populations, putting them at further risk of extinction.
At the University of Idaho, a recently published study aims to analyze the connection between cancer susceptibility and genes in wildlife populations using a cute, furry subject: the Catalina Island fox. A joint effort between Bioinformatics and Computational Biology (BCB) graduate Sarah Hendricks and BCB Director and Associate Professor Paul Hohenlohe, the study utilizes genome sequencing to identify a potential genetic basis to cancer susceptibility in the species for the very first time – a connection that could further decipher the role of cancer in other threatened wildlife populations.
A Catalina Island Conservation Effort
Located off the coast of California, Santa Catalina Island is one of multiple islands home to small populations of threatened wildlife. The Catalina Island fox, a relative of the mainland gray fox, is only found in numbers ranging from a few hundred to two thousand. The population was threatened by genetic bottlenecks due to predation and a canine distemper virus (CDV) epidemic in the 1990s, causing them to be classified as endangered in 2004. Thanks to human interference, the species has rebounded but remains threatened.
Cancers in wildlife are often complex and pose conservation concerns. After the rebound, cancer in the fox population began to be observed – but only on Santa Catalina Island, an oddity considering the populations on the neighboring islands. According to Hendricks, wildlife cancer is rare but also likely underreported. “Even with that, it’s still rare to find a whole species or whole population that get cancer, and this is one of the very few known cases where an entire population is affected with cancer,” she said.
Hendricks had been living on Catalina Island after completing her master’s degree. “While living there, I learned about these foxes that had a high rate of cancer,” she said. She stated that one could physically tell the difference between healthy and sick foxes because sick individuals would come into camp to forage and their normally upright ears would flop down. An earlier study attributed the cancer to ear mites, but couldn’t bridge a connection through chemicals, bacteria, or fungi – leaving genetics as the logical next step.
Research with a Vandal Flair
While working as a lab technician at UCLA, Hendricks got the idea to study the Catalina Island foxes. “I worked in a lab that focused on the genetics of canids and started thinking about the project,” she explained. “I decided to come to the University of Idaho for my PhD program. That’s when we really got the project started.”
Hendricks collected frozen fox genome samples from UC Davis and brought them back to the U of I. 32 genomes from Santa Catalina Island and San Clemente Island were sequenced, including individuals from where there was a high prevalence of disease and a control population.
With such a meager population, getting enough information from these genomes could have been a challenge. Hohenlohe, who had supervised the project, explained that the genome of a related species helped make the research happen. “Part of the reason we're able to do this in this small, threatened population is because the dog genome has been well sequenced and annotated, which means people have identified all the genes in the dog genome,” he said. “It's a close enough relative to these foxes that we were able to use information from that gene.”
The study hypothesized that the high incidence of ear tumors in the Catalina Island fox were the result of genetic variations that influenced cancer susceptibility. Through whole-genome sequencing, a connection would ideally be observed. However, the results were not what was expected. “We had the hypothesis that we would find some clear signature because it's such a high incidence of cancer compared to most populations and it's a genetically isolated population,” Hohenlohe said. “Our hypothesis was that we might find, for instance, one gene of major effect that explained that pattern. But we didn't find that." Instead, they found that cancer susceptibility is likely a polygenic trait – one that is influenced by two or more genes – which is typical in cancer and disease.
The study utilized many U of I resources, including those not offered at other universities. Hendricks wrote a grant application with Hohenlohe and received funding that provided ample financial support for her research. She also received funding from the Institute of Interdisciplinary Data Sciences (IIDS) that assisted her as a graduate student, as well as computational resources such as servers and programs to help prepare specimens. “It’s what IIDS does, but it’s very rare,” she said.
Hendricks also credited BCB seminar speakers for helping with research, another resource not offered by other college programs. “I could bring in people to talk to about the project, build collaborations with, and help problem solve as I completed the project,” she explained. “That’s also very rare from my experience.”
As part of the BCB program, students complete a lab rotation and can collaborate with other labs outside the U of I. Hendricks had a connection at Texas A&M through Brian Davis, who was experienced in studying cancer in animals. She spent a month at his lab learning how to analyze data and making connections. The opportunity provided her with the experience to connect with others while remaining part of the BCB program.
Looking to the Future
By understanding how genetic diversity differs in small populations, conservation practices can be informed and improved. Hendricks hopes studies like these will encourage wildlife organizations like state agencies to screen their populations for cancer. Doing so would allow for these phenomena to be monitored closely and more data for specific species - like the Catalina Island fox - to be collected. As for the future of the Catalina Island fox, new research is currently underway. A reference genome is currently being developed which would allow for more types of genetic mutations to be studied.
Further, the implications of the study reach beyond threatened populations to understanding cancer in domestic animals and even humans. “The connection would be a general better understanding of how cancer works,” Hohenlohe said. He stated that by taking the candidate genes of the study and determining how they affect cancer susceptibility and what their mutations might be, they could reveal more information about the mechanisms of cancer.
Despite the unique circumstances of the Catalina Island fox population, concepts and methods used in the study could be applied to other species. “We see it as a case study for cancer in wildlife populations,” Hohenlohe said. “It shows what we can do with whole genome sequencing and genomic data in small, threatened populations.”
Article by Rachel Wiedenmann,
IIDS Scientific Writing/Design Intern