The Great Duel: How Flies Outsmart Wasps with Sneaky Defense Tactics

However, at times, similar to the corporate arena, blatant theft can serve as a faster approach to achieving supremacy.

Researchers from the University of California, Berkeley, have revealed that multiple species of fruit fly have appropriated an effective defense mechanism from bacteria to evade predation by parasitic wasps, which in certain flies can transform half of all fly larvae into surrogate wombs for juvenile wasps—a horrific fate reminiscent of the creature in the 1979 film “Alien.”

Bacteria and other microorganisms are well-known for acquiring genes from different microbes or viruses; this phenomenon known as horizontal gene transfer is the root of problematic antibiotic resistance in disease-causing microbes. Nonetheless, it is considered to be less frequent in multicellular entities, such as insects and humans. Grasping the prevalence of this occurrence in animals and how these genes are repurposed and disseminated could aid scientists in comprehending the evolution of animal immune responses and might indicate avenues for human treatments to combat parasitic or infectious illnesses or cancer, itself a type of parasite.

“It’s a model for understanding how immune systems develop, encompassing our immune system, which similarly contains horizontally transferred genes,” stated Noah Whiteman, a UC Berkeley professor of molecular and cell biology, integrative biology, and director of the Essig Museum of Entomology on campus.

Last year, the researchers and their Hungarian collaborators utilized CRISPR genome editing to disable the gene responsible for the defense in a widely found fly species, Drosophila ananassae, discovering that nearly all the genetically altered flies perished due to predation by parasitic wasps.

In a recent investigation published on December 20 in the journal Current Biology, the biologists exhibited that this defense—a gene that encodes a toxin—can be integrated into the genome of the common laboratory fruit fly, Drosophila melanogaster, enabling them to resist parasitoid wasps as well. The gene essentially integrates into the fly’s immune system, serving as a weapon in its arsenal to repel parasites.

The findings underscore the significance of the appropriated defense for fly survival and accentuate a strategy that could potentially be more widespread in animals than scientists previously thought.

“This indicates that horizontal gene transfer is an underestimated method of rapid evolution in animals,” remarked UC Berkeley doctoral candidate Rebecca Tarnopol, lead author of the Current Biology article. “While horizontal gene transfer is acknowledged as a major catalyst for swift adaptation in microbes, these occurrences were presumed to be exceedingly rare in animals. But at least among insects, it appears to be relatively common.”

According to Whiteman, the paper’s senior author, “The research illustrates that to cope with the relentless influx of parasites that are constantly evolving new strategies to surmount host defenses, a reliable tactic for animals is to borrow genes from even more rapidly evolving viruses and bacteria, and this is precisely what these flies have accomplished.”

Gene transfer from virus to bacteria to fly

Whiteman investigates how insects evolve to counteract the toxins that plants generate to deter consumption. In 2023, he published a book titled “Most Delicious Poison,” discussing the plant toxins that humans have come to appreciate, such as caffeine and nicotine.

One particular plant-herbivore interaction he emphasizes is that between the ordinary fruit fly Scaptomyza flava and sour-tasting mustard plants, for instance, the cresses that thrive in streams across the globe.

“The larvae, which are the immature forms of the fly, inhabit the leaves of the plant. They act as leaf miners and create small trails in the foliage,” Whiteman explained. “They are genuine parasites of the plant, which attempts to eradicate them with its specialized chemicals. We examine that arms race.”

However, what he has learned likely pertains to numerous other insects, many among the most successful herbivores on the planet.

“These are relatively unnoticed flies, but when you consider that half of all existing insect species are herbivores, it’s a highly prevalent life history. Understanding this evolution is crucial for a broader comprehension of evolution in general concerning successful herbivores,” he noted.

Years ago, after sequencing the genome of the fly in search of genes that enable it to withstand mustard toxins, he stumbled upon an unusual gene that he learned was prevalent in bacteria. A review through previously published genome sequences revealed this same gene in a related fly, Drosophila ananassae, as well as in a bacterium residing within an aphid. Researchers investigating the aphid uncovered a complex narrative: the gene originates from a bacterial virus, or bacteriophage, that infects the bacteria living inside the aphid. The bacteriophage gene, expressed by the bacteria, grants the aphid immunity to a parasitic wasp that troubles it.

These wasps deposit their eggs inside the larvae, or maggots, and dwell there until the larvae metamorphose into immobile pupae, at which point the wasp eggs mature into wasp larvae that consume the fly pupa, ultimately emerging as adults.

When Tarnopol initially utilized gene editing to express the toxin gene in all cells of D. melanogaster, the entire population of flies perished. However, when she expressed the gene solely in specific immune cells, the fly gained resistance to parasites similar to its relative, D. ananassae.

Whiteman, Tarnopol, and their colleagues later discovered that the gene identified in the genome of D. ananassae—a fusion of two toxin genes, cytolethal distending toxin B (cdtB) and apoptosis inducing protein of 56kDa (aip56), which the researchers designated fusionB)—encodes an enzyme that degrades DNA.

To ascertain how this nuclease is capable of annihilating a wasp egg, the UC Berkeley researchers sought the expertise of István Andó at the Institute of Genetics of the HUN-REN Biological Research Centre in Szeged, Hungary, who had previously demonstrated that these same flies possess a cellular defense against wasp eggs that effectively isolates the eggs from the fly’s body and destroys them. Andó and his laboratory colleagues developed antibodies to the toxin, allowing them to trace it throughout the fly’s body and discovering that the nuclease essentially inundates the fly’s body to encapsulate and destroy the egg.

“We’ve been uncovering this vast, underutilized realm of humoral immune factors that might contribute to the immune system of invertebrates,” Tarnopol noted. “Our paper is among the first to demonstrate, at least in Drosophila, that this type of immune response could potentially be a common tactic for how natural adversaries like wasps and nematodes are managed. They tend to be significantly more lethal in nature compared to some of the microbial diseases that most researchers focus on.”

Whiteman and his colleagues continue to investigate the intricacies of these interactions between fly and wasp, alongside the cellular and genetic modifications that empowered the flies to produce a toxin without self-harm.

“If the gene is activated in the incorrect tissue, the fly will perish. That gene will never propagate through populations due to natural selection,” Whiteman remarked. “However, if it integrates into a region in the genome that’s near an enhancer or some regulatory element that expresses it a little in fat body tissue, then you can envision how it could gain a significant edge swiftly, providing an extraordinary advantage.”

Horizontal gene transfer in any organism would present similar challenges, he noted, but in the predator-prey arms race, the potential benefits might outweigh the drawbacks.

“When you’re just a humble fruit fly, how do you contend with these pathogens and parasites that are evolving rapidly to exploit you?” he questioned. “One method is to adopt genes from bacteria and viruses since they are swiftly evolving. It’s an ingenious strategy—rather than waiting for your own genes to assist you, you acquire them from other organisms that evolve more quickly than you do. And that appears to have occurred many times independently among insects, given that so many diverse species have assimilated this gene. It provides us with insights into a new form of dynamism that is taking place even in animals with merely innate immune systems and lacking adaptive immunity.”

Whiteman’s research received funding from the National Institute of General Medical Sciences of the National Institutes of Health (R35GM119816). Additional co-authors of the paper include Josephine Tamsil, Ji Heon Ha, Kirsten Verster, and Susan Bernstein from UC Berkeley, Gyöngyi Cinege, Edit Ábrahám, Lilla B. Magyar, and Zoltán Lipinszki from Hungary, along with Bernard Kim from Stanford University.