Tasmanian devils evolve resistance to facial cancers

Facing extinction, the devils have fought back.

A transmissible facial cancer has devastated Tasmanian devil (Sarcophilus harrisii) populations. Devils have seen localized population declines exceeding 90 percent and an overall species decline of more than 80 percent in less than 20 years, with some models predicting extinction. Despite this, devil populations persist in disease stricken areas.

Andrew Storfer, Washington State University and his team have found evidence of an evolutionary resistance to the tumors in their Nature Communications study. They identify two genomic regions that contain genes related to immune function or cancer risk in humans across numerous devil populations. We spoke to Storfer about the findings.

ResearchGate: What is the current state of the Tasmanian devil population?

Andrew Storfer: Since the emergence of devil facial tumor disease, Tasmanian devils have experienced localized declines of over 90 percent and a species-wide decline exceeding 80 percent, they are listed as endangered.

ResearchGate: What makes this cancer so dangerous? How does this cancer spread and what causes it?

Storfer: The cancer is nearly 100 percent fatal because it grows on the face to the point that animals starve or can't breathe. It is spread by biting - Tasmanian devils frequently bite each other on the face during social interactions. It is caused by an infectious cell line, which means the cancer is directly transmitted from individual to individual.

ResearchGate: What did your study find?

Storfer: We scanned the genomes of 294 Tasmanian devils in three populations assessing their genetic composition before the cancer arrived and after a few generations of cancer presence. We found evidence of evolution in two small portions of the genome containing seven genes. Within this portion particular variants significantly increased in frequency four to six generations after the diseases’ arrival. Remarkably, this evolution was quite rapid, and five of the seven genes were associated with immune response and cancer in other mammals, including humans.

Tasmanian Devil. Credit: Menna Jones
Tasmanian Devil. Credit: Menna Jones

ResearchGate: Can you briefly take us through how you arrived at this finding?

Storfer: We used a technique called "RAD-seq" whereby restriction enzymes are used to cut the genome into many small pieces. These DNA fragments are sequenced on a "next-generation" DNA-sequencer, aligned, and differences in single DNA base pairs (called SNPS, or single-nucleotide polymorphisms) are identified. We generated 90,000 of them, covering approximately 20 percent of the Tasmanian devil genome and spread roughly evenly across the six autosomes (non-sex chromosomes).  We then looked for the highest changes in frequency of any of these SNPS in the comparison of pre- and post-disease population samples. We only chose SNPS that changed in all three localities we studied. We used independent statistical analyses to further test, and in this case, corroborate, our results. Finally, we characterized the genes nearby the SNPS that are within areas of the genome that are inherited together.

ResearchGate: How confident are you in the survival of Tasmanian devils?

Storfer: I can't say for sure, but demographic models already predicted extinction in some populations that persist. Our results make us hopeful because the devil has evolved and the evolutionary response is promising.

ResearchGate: Do you have any idea how these gene sequences that likely cause immunity developed?

Storfer: They already existed in the Tasmanian devil as part of their immune system. They increased in frequency due to natural selection. That is, the individuals with particular forms of these genes (alleles) survived and reproduced disproportionately to those that lacked the specific variants when disease was present.

ResearchGate: Are you still worried about the Tasmanian devil population?

Storfer: We are certainly still worried. The disease has infected nearly all known populations of devils and is still causing dramatic declines in newly infected populations. Tasmanian devils have declined over 80 percent in numbers. Fortunately, there is an off-island captive breeding program that will be used to reintroduce devils in the case of extinction. Researchers (Kathy Belov at University Sydney and Greg Woods at the Menzies institute in Tasmania) are experimenting with an immune-boosting strategy that may provide protection against the cancer. The first individuals have been released into the wild, but it is too early to tell whether they are protected or not.

Image courtesy of flickr