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How Bats’ Genomes May Help Them Avoid Cancer and Survive Viruses

Artibeus jamaicensis, the Jamaican fruit bat.
Artibeus jamaicensis, the Jamaican fruit bat. Credit: Brock and Sherri Fenton/Genome Biology and Evolution
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A new study has analyzed the genomes of bats to investigate their ability to tolerate viral infections and avoid cancer – findings that could have implications for our knowledge of human cancers as well as virus transmission from animals. The research is published in Genome Biology and Evolution.

Bats have an “unusual” immune response

Mice are some of the most commonly used animals in experiments that inform human health – but another mammal may be even more informative. Enter the bat – famed as the only mammal capable of flight, but also for its longevity, low cancer rates and strong immune systems.

Bats’ unusual immune systems allow them to better tolerate viral infections, though this can also spell danger for human health. They can play a key role in the spillover of viral infections into humans.

Studying bats’ immune systems could reveal more about cancer development and provide insights into preventing the spread of disease from animals to people. However, research efforts to uncover exactly what makes bats’ immune systems tick have been hampered by small sample sizes and limitations in genetic analysis approaches.

In the current study, researchers utilized long-read sequencing to carry out a comprehensive genomic analysis of two bat species, adding these to existing high-quality genomes to characterize the genetic features associated with their low cancer rates and robust immune responses.

Uncovering genetic adaptations

The study’s lead author, Dr. Armin Scheben, explained that the team compared 13 existing bat genomes – plus their 2 new additional genomes – against those of humans, mice, dogs, pigs and horses. “Our study increased the quantity of data by sampling 15 bat species and also increased the quality of data by using more complete genomes mainly generated with long-read DNA sequencing,” said Scheben, a postdoctoral fellow at Cold Spring Harbor Laboratory, speaking to Technology Networks.

“We looked for changes in both gene gains and losses as well as more subtle adaptive changes in DNA sequences that make bats different from the other mammals,” he added.

They investigated the positive selection of “cancer-related” genes – genes included either in the Tumor Suppressor Database or the Catalogue of Somatic Mutations in Cancer. They found evidence for positive selection of 33 tumor suppressor genes and 6 DNA repair genes, suggesting a link to the bats’ low rates of cancer and increased longevity. Strikingly, cancer-related genes were also enriched more than twofold in bat genomes compared to those of other mammals.

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The researchers also found changes in type I interferon (IFN) genes, which are part of the innate immune system and help to activate antiviral responses. They observed a loss of IFN-α genes, while IFN-ω were relatively unaffected. By relying on the potentially more potent IFN-ω instead of IFN-α, bats may have improved antiviral responses, possibly contributing to their ability to tolerate viruses that can be transmitted to humans.

“We show that the bat immune system differs strongly from our own in a gene region known as the type I interferon locus,” Scheben said. “By targeting this gene region and the proteins it produces with therapeutics, we may be able to treat infectious diseases better in humans. Similarly, bats show signs of genetic adaptations in many anti-cancer genes, which could inspire therapeutics to treat cancer.”

Exploring the underlying mechanisms

Scheben goes on to explain that, while the research is somewhat limited by not experimentally testing these genetic mechanisms, he considers the study to be more of a “hypothesis generator”. To dig deeper into these findings, the team is now working on developing what he calls “batified” mouse models – mice genetically modified to carry bat variants of genes.

“By testing these ‘batified’ mice, we aim to better understand how bats resist infections and cancer,” Scheben explains. “These findings can help other researchers, at universities and in industry, to prioritize specific genes and gene variants as targets for therapeutics.”

Reference: Scheben A, Ramos OM, Kramer M, et al. Long-read sequencing reveals rapid evolution of immunity- and cancer-related genes in bats. 2023. Genome Biol. Evol. doi: 10.1093/gbe/evad148

Dr. Armin Scheben was speaking to Dr. Sarah Whelan, Science Writer for Technology Networks.