Outsmarting Danger: The Art of Borrowing Defense Mechanisms to Outsmart Predators

In the ongoing conflict between parasites and their hosts, it was previously believed that innovation was essential for a successful assault or defense that would surpass rivals. However, as seen in the business sector, overt theft can often be a more efficient route to achieve supremacy.

Researchers from the University of California, Berkeley, have revealed that several fruit fly species have appropriated a successful defense mechanism from bacteria to avoid predation by parasitic wasps, which can convert nearly half of all fly larvae into substitutes for their offspring—a grim outcome that inspired the alien creature in the 1979 film “Alien.”

Bacteria and other microbes are well-known for acquiring genes from different microbes or viruses; this so-called horizontal gene transfer is responsible for the alarming development of antibiotic resistance in harmful microbes. However, it is considered to be rare among multicellular organisms, including insects and humans. Gaining insights into the prevalence of this phenomenon in animals and the manner in which these genes are utilized and disseminated can aid scientists in understanding the evolution of immune defenses in animals and might indicate potential avenues for human treatments against parasitic or infectious diseases, as well as cancer, which functions as a sort of parasite.

“It serves as a model for comprehending how immune systems evolve, including our own immune system which also features horizontally transferred genes,” stated Noah Whiteman, professor of molecular and cell biology, as well as integrative biology at UC Berkeley, in addition to being the director of the Essig Museum of Entomology at the campus.

In the previous year, the researchers and their collaborators in Hungary employed CRISPR genome editing to disable the gene responsible for the defense mechanism in a widely known fly species, Drosophila ananassae, and observed that nearly all the genetically modified flies fell prey to parasitic wasps.

In a recent study published on December 20 in the journal Current Biology, the biologists illustrated that this defense—a gene encoding a toxin—can be integrated into the genome of the common laboratory fruit fly, Drosophila melanogaster, to confer resistance against parasitoid wasps as well. The gene essentially becomes an integral part of the fly’s immune system, serving as one of its weapons to repel parasites.

The findings underscore the vital role of the appropriated defense in the survival of flies and emphasize a strategy that may be more prevalent among animals than previously believed.

“This illustrates that horizontal gene transfer is a misunderstood mechanism underlying rapid evolution in animals,” remarked UC Berkeley doctoral candidate Rebecca Tarnopol, the primary author of the Current Biology article. “While people recognize horizontal gene transfer as a key factor in rapid adaptation among microbes, such occurrences were considered to be extremely rare in animals. However, at least in the case of insects, it appears to be quite common.”

Whiteman, the senior author of the paper, noted, “The research indicates that to keep pace with the onslaught of parasites that are continuously evolving new methods to overcome host defenses, a viable strategy for animals is to borrow genes from even more swiftly evolving viruses and bacteria, which is precisely what these flies have accomplished.”

Gene transfer from virus to bacteria to fly

Whiteman investigates how insects adapt to resist the toxins produced by plants to deter consumption. In 2023, he published a book titled “Most Delicious Poison,” which discusses the plant toxins that humans have come to savor, such as caffeine and nicotine.

One interaction between plants and herbivores that he focuses on is the connection between the common fruit fly Scaptomyza flava and sour-flavored mustard plants, like the cresses found in rivers worldwide.

“The larvae, which represent the immature stages of the fly, inhabit the leaves of the plant. They mine the leaves, leaving behind small trails,” Whiteman explained. “They’re genuine parasites of the plant, which is attempting…to eliminate them with its tailored compounds. We investigate that competitive dynamic.”

What he has discovered, nevertheless, probably pertains to numerous other insects, which are among the most successful herbivores on the planet.

“These are rather obscure little flies, yet considering that fifty percent of all existing insect species are herbivores, it’s quite a prevalent life history. Grasping the evolution of that is crucial for comprehending evolution as a whole regarding the success of herbivores,” he stated.

A few years back, after sequencing the fly’s genome in search of genes that permit it to withstand mustard toxins, he identified an atypical gene that he found to be widely present in bacteria. A review of previously published genomic sequences brought up the same gene in a related fly, Drosophila ananassae, as well as in a bacteria residing within an aphid.

Scientists investigating the aphid revealed a complex narrative: The gene actually derives from a bacterial virus, or bacteriophage, that infects the bacteria living inside the aphid. The gene from the bacteriophage, activated by the bacteria, confers resistance to a parasitic wasp that harasses the aphid.

These wasps deposit their eggs within the larvae, or maggots, remaining until the larvae transform into immobile pupae, at which stage the wasp eggs develop into wasp larvae that consume the fly pupa, eventually surfacing as adults.

When Tarnopol initially utilized gene editing to express the toxin gene throughout all cells in D. melanogaster, all the flies perished. However, when Tarnopol expressed the gene solely in specific immune cells, the fly exhibited resistance to parasites akin to its relative, D. ananassae.

Whiteman, Tarnopol, and their associates later found that the gene located in the genome of D. ananassae—a fusion between two toxin genes, cytolethal distending toxin B (cdtB) and apoptosis inducing protein of 56kDa (aip56), designated as fusionB by the researchers—encodes for an enzyme that cleaves DNA.

To understand how this nuclease can exterminate a wasp egg, the UC Berkeley researchers sought assistance from István Andó at the Institute of Genetics of the HUN-REN Biological Research Center in Szeged, Hungary, which had earlier demonstrated that these very flies possess a cellular defense mechanism against wasp eggs that effectively encases the eggs from the fly’s body and destroys them.

Andó and his lab team produced antibodies to the toxin that enabled them to trace it through the fly’s body and discovered that the nuclease essentially inundates the fly’s body to encircle and eliminate the egg.

“We have been uncovering this vast, untouched world of humoral immune factors that may play a role in the immune system of invertebrates,” Tarnopol stated. “Our publication is one of the first to demonstrate, at least in Drosophila, that this kind of immune response might be a common strategy for managing competing threats like wasps and nematodes. They are exponentially more lethal in the wild compared to some microbial infections that most researchers focus on.”

Whiteman and his team continue to investigate the intricacies of these interactions between flies and wasps, as well as the cellular and genetic modifications that have enabled the flies to produce a toxin without harming themselves.

“If the gene is activated in an inappropriate tissue, the fly will perish. That gene will never proliferate through populations via natural selection,” Whiteman explained. “However, if it integrates into a genomic area that’s close to some enhancer or regulatory element that expresses it slightly in fat body tissue, then you can comprehend how it can gain this advantage rapidly, you see this incredible leverage.”

Horizontal gene transfer in any organism would present similar dilemmas, he added, but in the evolutionary battle between predator and prey, it might be beneficial.

“When you find yourself a destitute little fruit fly, how do you navigate these swiftly changing pathogens and parasites that are evolving to exploit you?” he remarked. “One approach is to appropriate genes from bacteria and viruses because they are evolving quickly. It’s a clever tactic—rather than anticipating your own genes to assist you, acquire them from other organisms that are evolving at a much faster pace than your own. And it appears this has occurred numerous times independently in insects, considering the variety of species that have incorporated this gene.

“It presents us with a perspective of a new type of dynamism that is happening even in organisms that possess only innate immune mechanisms and lack adaptive immunity.”