Tasmanian devils face threats from rapidly evolving facial tumors

TAsmanian devil populations have declined in recent decades due to two contagious facial tumors that cause debilitating growths. Now, together with an international group of scientists and organisations, researchers from the University of Cambridge have conducted a large study on genetic sequencing published in Scienceand found that one of those tumors is evolving at an alarming rate and could pose a major threat to Tasmania’s main carnivore.¹

This study is the first to trace the evolution of the two cancers, creating a detailed account of when the cancers appeared, how they spread across the landscape, and most importantly, what mutations helped them spread over time.

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Carolyn Hogg, a biologist at the University of Sydney who was not involved in the study, said the research team has generated useful tools for studying devils. You can make tremendous progress in understanding how species work [and] disease moves across the landscape and how disease mutates and changes, with genomic data, he said.

Evil diseases

Tasmanian devils are the largest carnivorous marsupials in the world, native only to Tasmania, an island off the coast of southeastern Australia. For more than 30 years, these marsupials have battled two lethal facial tumors, Devil’s Facial Tumor 1 (DFT1) and Devil’s Facial Tumor 2 (DFT2). A unique feature of these tumors is that they are spread primarily through bites, a common occurrence in devils during fights for mates and food. Transmissible cancers are extremely rare in nature, making devils important models for studying cancer evolution.

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Since its discovery in 1996, DFT1 has spread throughout Tasmania and almost the entire devil population, said study co-author Elizabeth Murchison, a cancer geneticist at the University of Cambridge. As a result, the devil population has declined by 60%, although recent research has shown that devils may develop a resistance to the disease.² DFT2 was discovered in 2014 and has only spread to a small corner of southeastern Tasmania, but little is known about this second cancer.

After studying devils for decades, Murchison wanted to compare the evolution of the two tumors by looking in detail at the mutations that occurred in the populations of these tumors. Basically, he wanted to understand the common characteristics and mutations in these transmissible cancers that help them spread.

Twin threats

Murchison had previously put together a reference genome of the Tasmanian devil, but gaps remained. Advances in sequencing technology allowed his team to create an updated version of the reference genome for this study to better understand the genes conserved across individuals. The team also sequenced cells from 78 DFT1 and 41 DFT2 Tasmanian devil tumors. Then by comparing the tumors to the reference genome, the team built a phylogenetic tree of the two tumours. This allowed them to pinpoint when the tumors first appeared, when the mutations occurred and which mutations shared the two diseases.

The first surprise was that DFT2 acquires mutations about three times faster than DFT1, Murchison said.

That’s likely bad news for the devils, he added, because DFT2 may be more likely to acquire mutations that enhance its spread. However, DFT2 has not yet become widespread. More work needs to be done to understand the scale of this threat, according to Hogg.

The sequencing results suggest that DFT1 emerged in 1986, 10 years before it was first detected in a female devil in northeastern Tasmania. The analysis also provided clues about how the disease spread across the island, revealing that one super-widespread female initially infected about six other people, resulting in at least six major DFT1 variants.

DFT2 emerged in 2011, three years before researchers spotted a male devil with an infectious cancer in the southeast corner of the island.

Some of the same mutations have appeared repeatedly, indicating that selection pressures may be driving their spread. In several cases, they found that DFT2, which originated in a male devil, had developed a mutation that deleted its Y chromosome, possibly to make it easier to spread to female devils. The researchers also found evidence in both tumors for two dimer-forming, cell-surface tyrosine kinase proteins called platelet-derived growth factor a (PDGFA) and platelet-derived growth factor b (PDGFB). ), which are involved in cell growth and also implicated in cancer in other species, including humans.

DFT1 and DFT2 are long-lived and can be sampled repeatedly over time, according to Murchison. He hopes the findings will help conserve the Tasmanian devils. We can get some insight into the temporal evolution of cancer, he said she. This helps us understand what might happen in the future.

References

1. StammnitzMR, et al. The evolution of two transmissible tumors in Tasmanian devils. Science. 2023;380(6642):283-293.
2. EpsteinB, et al. Rapid evolutionary response to a transmissible cancer in Tasmanian devils.Nat. Common. 2016;7(1).