Many flies face threats from parasitic wasps, which deposit their eggs in fly larvae, utilizing them as living incubators for their young. A specific fly species has developed a defense against these wasps by acquiring a gene from bacteria that came from bacteriophages. Researchers from the University of California, Berkeley, have successfully transferred this gene into other fly species, providing them with resistance against wasps. This finding suggests that the process of horizontal gene transfer may happen more frequently among animals than previously believed.
The ongoing arms race between parasites and their hosts has often led to the idea that innovative adaptations are crucial for either offensive or defensive advantages in this competition.
However, similar to the business world, outright gene theft can be a faster and more effective means of gaining an advantage.
Biologists from UC Berkeley have discovered that various fruit fly species have acquired a successful defense mechanism from bacteria, allowing them to resist parasitic wasps that can convert nearly half of the larvae into hosts for wasp offspring—an unsettling fate reminiscent of the 1979 horror film “Alien.”
Bacteria and microbes are known for swapping genes with one another or with viruses through what is called horizontal gene transfer, which contributes to the spread of antibiotic resistance among pathogens. However, it’s generally considered rare in complex organisms such as insects and humans. Understanding how prevalent this process is in animals and how these genes are shared could enhance scientific knowledge of animal immune systems and may lead to new treatments for diseases, including parasitic infections and cancer, which can be viewed as a form of parasitism.
“This research offers insight into the evolution of immune systems, including our own, which also contains genes that have been transferred horizontally,” noted Noah Whiteman, a UC Berkeley professor specializing in molecular and cell biology, as well as integrative biology, and director of the Essig Museum of Entomology.
In 2022, the team and their colleagues in Hungary used CRISPR technology to disable the gene responsible for protective measures in the widely distributed fly species Drosophila ananassae. The results showed that nearly all modified flies succumbed to attacks from parasitic wasps.
In a recent study published on December 20 in the journal Current Biology, researchers demonstrated that introducing this protective gene—responsible for producing a toxin—into the common lab fruit fly, Drosophila melanogaster, could also grant them resistance against parasitoid wasps. This gene effectively integrates into the fly’s immune response, enhancing its ability to combat parasites.
The findings illustrate the critical role that this borrowed defense plays in fly survival and suggest that such strategies may be more commonplace in the animal kingdom than previously recognized.
“This study reveals that horizontal gene transfer is a significant but overlooked mechanism facilitating rapid evolution in animals,” remarked Rebecca Tarnopol, a UC Berkeley PhD student and lead author of the Current Biology article. “While this process is well-acknowledged in microbes as a key driver of rapid adaptation, it was believed to be rare in animals. However, in insects, it appears to be relatively frequent.”
According to Whiteman, the senior author of the study, “This research indicates that to counteract the constant evolution of parasites that develop new strategies to bypass host defenses, animals can effectively borrow genes from swiftly evolving viruses and bacteria. This is precisely what these flies have accomplished.”
Gene transfer from viruses to bacteria to flies
Whiteman’s research focuses on how insects evolve resistance against plant toxins designed to deter herbivory. He published a book in 2023 titled “Most Delicious Poison,” discussing the plant toxins, such as caffeine and nicotine, that humans enjoy.
One notable interaction he studies is between the fruit fly Scaptomyza flava and bitter mustard plants, which include cresses found globally.
The larvae develop within the plant leaves and mine trails throughout, acting as true parasites while the plant attempts to fend them off with specialized chemicals. “We examine this ongoing evolutionary struggle,” Whiteman explained.
What he has learned, however, likely applies to a wide variety of insects, which account for a significant proportion of successful herbivores on Earth.
“Though these flies may seem insignificant, considering that half of all living insect species are herbivores, this lifestyle is quite common. Understanding how this evolved is vital for grasping evolutionary principles as a whole,” he added.
After sequencing the genome of the fly while looking for genes that enable resistance against mustard toxins, he discovered an unusual gene prevalent in bacteria. Further investigation revealed this gene also existed in a related fly, Drosophila ananassae, as well as in bacteria residing in aphids. Research on aphids showed the gene originated from a bacteriophage that infects the bacterial inhabitants of aphids, enabling them to fend off parasitic wasps.
These wasps lay eggs within the larvae, remaining there until the larvae transform into immobile pupae. At that stage, the wasp larvae consume the fly pupae, ultimately emerging as adults.
Initially, when Tarnopol applied gene-editing to introduce the toxin gene in all cells of D. melanogaster, all the flies perished. However, limiting expression of the gene to specific immune cells allowed the flies to gain resistance comparable to their relative, D. ananassae.
Through subsequent research, Whiteman, Tarnopol, and their peers identified that the gene present in D. ananassae—a fusion of two toxin genes, cytolethal distending toxin B (cdtB) and apoptosis inducing protein of 56kDa (aip56), which they designated fusionB—encodes an enzyme capable of damaging DNA.
To understand how this nuclease could eliminate wasp eggs, UC Berkeley researchers contacted István Andó at the Institute of Genetics, HUN-REN Biological Research Centre in Szeged, Hungary, who had previously shown that these same flies employ a cellular defense mechanism to isolate wasp eggs and exterminate them. Andó’s team created antibodies for the toxin to trace its distribution within the fly’s body, discovering that the nuclease surrounds and destroys the wasp egg.
“We have uncovered an enormous, previously untapped universe of humoral immune factors that may contribute to the immune systems of invertebrates,” Tarnopol stated. “Our research is one of the first to demonstrate that this type of immune response might be a common strategy against natural enemies like wasps and nematodes, which often pose a greater threat than many typical microbial infections studied.”
Whiteman and his colleagues continue to investigate the complex interactions between flies and wasps and the genetic and cellular adaptations that enable the flies to produce a toxin without harming themselves.
“If the gene is activated inappropriately, the fly is doomed. It will never propagate through populations by natural selection,” Whiteman explained. “However, if it integrates into a favorable part of the genome near an enhancer or regulatory sequence allowing slight expression in fat body tissues, you can easily understand how it gives the fly a significant advantage.”
The challenges of horizontal gene transfer apply to any organism, but in the predator-prey conflict, such adaptations may be invaluable.
“For a defenseless little fruit fly, how can you confront these swiftly evolving threats?” he asked. “One effective method is to adopt genes from rapidly changing bacteria and viruses. This clever tactic circumvents the wait for one’s own genes to provide assistance, opting instead to utilize those from other organisms that adapt more quickly. This phenomenon appears to have occurred multiple times independently in insects, as numerous species have acquired this gene. It paints a picture of a fresh dynamism at work, even within animals possessing only innate immune systems devoid of adaptive immunity.”
Whiteman’s work received funding from the National Institute of General Medical Sciences at the NIH (R35GM119816). Co-authors of the paper include Josephine Tamsil, Ji Heon Ha, Kirsten Verster, Susan Bernstein of UC Berkeley, Gyöngyi Cinege, Edit Ábrahám, Lilla B. Magyar, and Zoltán Lipinszki of Hungary, along with Bernard Kim of Stanford University.
