Fruit flies steal bacterial protection to survive parasitic wasps

In the constant arms race between parasites and their hosts, innovation was believed to be the key to an effective attack or defense that outperformed the competition.

But sometimes, as in the corporate world, outright theft can be a quicker way to achieve dominance.

Biologists at the University of California, Berkeley, have shown that several species of fruit flies have hijacked effective bacterial defenses to survive predation by parasitic wasps, which in some flies can turn half of all fly larvae into surrogate wombs for the young wasps; a gruesome fate that inspired the creature in the 1979 film “Alien.”

Bacteria and other microbes are notorious for stealing the genes of other microbes and viruses; this so-called horizontal gene transfer is the source of the trouble antibiotic resistance among pathogenic microorganisms. However, it is thought to be less common in multicellular organisms such as insects and humans. Understanding how common this phenomenon is in animals and how these genes are co-opted and shared could help scientists understand the evolution of animal defense mechanisms and point the way to therapies in humans fighting parasitic or infectious diseases or cancer, itself a type of parasite .

It is a model for understanding the evolution of immune systems, including our own immune system, which also contains horizontally transferred genes.”

Noah Whiteman, professor of molecular and cellular biology and integrative biology at the University of California, Berkeley, and director of the Essig Museum of Entomology on campus

Last year, scientists and their colleagues in Hungary used CRISPR genome editing to knock out a defense gene in one widespread fly species and found that almost all of the genetically modified flies died from predation by parasitic wasps.

In a new study published December 20 in the journal, biologists showed that this defense -; gene encoding toxin -; they can be edited in the genome of common laboratory fruit flies to make them resistant to parasitoid wasps as well. The gene essentially becomes part of the fly’s immune system, one of the weapons in its arsenal to fight off parasites.

The results show how important stealth defense is to surviving flying, and highlight a strategy that scientists suspect may be used more often in animals.

“This shows that horizontal gene transfer is an underappreciated means of rapid evolution in animals,” said Rebecca Tarnopol, a doctoral student at the University of California, Berkeley, and first author of the paper. “People appreciate horizontal gene transfer as one of the main drivers of rapid adaptation in microbes, but such events were thought to be extremely rare in animals. But they seem to happen quite often, at least in insects.”

According to Whiteman, senior author of the paper: “The study shows that to keep up with the flood of parasites that are constantly developing new ways to overcome host defenses, a good strategy for animals is to borrow genes from even faster-evolving viruses and bacteria, and that’s exactly what these flies did. “

Gene flow from virus to bacteria so they can fly

Whiteman studies how insects evolve to resist toxins produced by plants to prevent being eaten. In 2023, he published the book “The Tastiest Poison” about plant toxins that humans like, such as caffeine and nicotine.

One of the interactions between plants and herbivores that he focuses on is the interaction between the common fruit fly and sour mustard plants, such as cress, that grow in streams around the world.

“The larvae, the immature stages of the fly, live in the leaves of the plant. They dig up the leaves and leave little marks in the leaves,” Whiteman said. “These are true parasites of the plant, and the plant tries to kill them using specialized chemicals. We are investigating this arms race.”

But what he learned likely applies to many other insects, among the most successful herbivores on Earth.

“These are little-known flies, but if you think about the fact that half of all living insect species are herbivores, you have a very common life history. Understanding their evolution is really important to understanding evolution in general in terms of how successful herbivores are. they are,” he said.

Several years ago, after sequencing a fly’s genome to look for genes that would enable it to resist mustard toxins, he discovered an unusual gene that he learned was widespread among bacteria. A search of previously published genome sequences found that the same gene is present in a related fly as well as in a bacterium that lives inside aphids. Scientists studying the aphid have discovered a complicated story: the gene actually comes from a bacterial virus, or bacteriophage, that infects bacteria living inside the aphid. The bacteriophage gene expressed by the bacteria makes the aphid resistant to the parasitic wasp that plagues it.

These wasps lay their eggs inside the larvae, or worms, and remain there until the larvae turn into immobile pupae, at which point the wasp eggs mature into wasp larvae, which eat the fly pupae, eventually emerging as adults.

When Tarnopol first used gene editing to express the toxin gene in all cells, all the flies died. However, when the gene was expressed in only some immune cells in Tarnopol, the fly became as resistant to the parasites as its cousin.

Whiteman, Tarnopol and their colleagues then discovered that the gene found in the genome -; a fusion of two toxin genes () and (), which researchers called -; encodes a DNA-cutting enzyme.

To find out how this nuclease is able to kill a wasp egg, researchers from the University of California, Berkeley contacted István Andó of the Institute of Genetics of the HUN-REN Biological Research Center in Szeged, Hungary, who had previously shown that the same flies have cellular defense against wasp eggs, which essentially separates the eggs from the fly’s body and kills them. Andó and his lab colleagues created antibodies against the toxin that allowed them to track it throughout the fly’s body, and discovered that the nuclease essentially floods the fly’s body, surrounding and killing the egg.

“We have discovered a vast, untapped world of humoral immune factors that may play a role in the invertebrate immune system,” Tarnopol said. “Our work is among the first to show, at least in Drosophila, that this type of immune response may be a common mechanism by which we deal with natural enemies such as wasps and nematodes. They are inherently much deadlier than some of the bacterial infections most people deal with.”

Whiteman and his colleagues are still investigating the complexity of the fly-wasp interaction and the cellular and genetic changes that allowed the flies to synthesize toxins without killing themselves.

“If the gene is expressed in the wrong tissue, the fly will die. This gene will never make its way through the population through natural selection,” Whiteman said. “But if it lands in a place in the genome that is close to some enhancer or regulatory component that expresses it a little bit in adipose tissue, then you can see how it can get that leg up really quickly, you get this incredible advantage. “

Horizontal gene transfer in any organism would pose similar problems, he said, but in an arms race between predator and prey it could pay off.

“When you’re a poor little fruit fly, how do you deal with the pathogens and parasites that are quickly evolving to take advantage of you?” he said. “One way is to borrow genes from bacteria and viruses because they evolve quickly. It’s a brilliant strategy: instead of waiting for your own genes to help you, get them from other organisms that are evolving faster than themselves. this seems to have happened many times independently in insects, given that so many different species have adopted this gene. This gives us a picture of a new kind of dynamic that occurs even in animals that only have an innate immune system, not May. have adaptive immunity.”

Whiteman’s work was funded by the National Institute of General Medical Sciences of the National Institutes of Health (R35GM119816). Other co-authors of the paper include Josephine Tamsil, Ji Heon Ha, Kirsten Verster and Susan Bernstein from the University of California, Berkeley, Gyöngyi Cinege, Edit Ábrahám, Lilla B. Magyar and Zoltán Lipinszki from Hungary, and Bernard Kim from Stanford University.