When Parasites Attack, Flies Diversify Their Babies’ Genes

Imagine an animal that reproduced by budding off genetically identical clones. This asexual creature doesn’t have to bother with finding or attracting mates: it is a self-contained factory for making more of itself. This sounds like a recipe for success, but asexual animals are far from successful. They exist, but they tend to be rare and precarious twigs on the tree of life—recently evolved, and likely to snap off at any time. By and large, the vast majority of animal life practices sex.

The asexual lifestyle falters because it presents a sitting target. If every new generation is genetically identical to the last, then predators, parasites, and rivals can easily evolve ways of outmanoeuvring them all.

Sex mixes things up—literally so. When the genes from a mother and father unite in their offspring, they are broken up, shuffled, and rejoined in new ways, through a process called recombination. This creates variety. In the recombinant youngsters, parasites face a diverse range of targets, and are unlikely to be able to hit all of them at once. The targets also move. Each bout of sex creates new combinations of genes that parasites must then adapt to. And when they do so, the combinations change again. As the Red Queen of Lewis Carroll’s Wonderland said, “It takes all the running you can do, to keep in the same place.”

These “Red Queen dynamics” have been a familiar part of evolutionary biology for many decades. But Nadia Singh from North Carolina State University has found a new and dramatic twist on the idea. She showed that fruit flies, after facing infectious bacteria or body-snatching wasps, produce more diverse offspring. It turns out that when parasites are around, the flies can somehow ensure that the next generation’s set of genes—their genotype—is even more thoroughly shuffled than usual.

“One way to look at it is that if parasites are specialising on any particular host genotype, then being different at all is good,” says Todd Schlenke from Reed College, Oregon, who was also involved in the study. “As long as you’re different from your parents, you’ll do well.”

There have been some hints of this before. Over the last century, scientists have found that all kinds of environmental factors, including temperature, stress, and age, can affect the frequency of recombination. In plants, those factors include infections. “I have always thought about whether the same is true for animals,” says Schlenke.

To find out, Singh worked with flies that had mutations in two genes that sit very close to one another: ebony, which darkens their skin; and rough, which changes their eyes from regularly dimpled domes into uneven and chaotic ones. Through clever breeding, Singh created strains of flies where the mutations were linked, so individuals either had both rough eyes and dark bodies, or neither. If she continued to breed them, and ended up with flies with just one mutation—say, rough eyes but light bodies—she knew they were the result of recombination. In these recombinant insects, the normal copy of one gene had been shuffled next to the mutant version of its neighbour.

Using these flies, Singh showed that when females are infected with an opportunistic bacterium before they could mate, they produced around 15 percent more recombinant larvae. Schlenke showed that an attack from a parasitic wasp could do the same. The wasp lays its egg inside the fly larva, which will be eaten from the inside-out unless its immune system can destroy the invader. If they survive, mature, and mate, they also produce more recombinant larvae than any flies which didn’t have to endure trial-by-wasp. By contrast, merely wounding the flies with needles had no effect; it was specifically infections, whether by bacterium or wasp, that led to more recombination.

And actually, they didn’t lead to more recombination. Schlenke and Singh found signs that the rate of shuffling doesn’t go up. What actually happens is even weirder. In a female’s reproductive system, several potential cells could turn into eggs, ready to be fertilised by males. It seems that, after infections, the females can somehow prioritise those cells in which recombination has already happened.

“It’s like the parents ‘know’ which of the cells are the recombinant ones and they’re preferentially making those into the embryos.  Or they know which are the non-recombinant cells and delete them,” says Schlenke. “It sounds crazy but it’s the least crazy of the crazy explanations.” It’s still unclear how the females actually pull this off.

“It’s almost like genetic engineering,” he adds. “People think: oh, what if you could engineer your child to be smarter, or have brown eyes, or whatever. That’s sort of what’s happening here. These parents are altering the genotypes of their offspring. They’re not specialising and going for a particular genotype, but they’re going for genotypes that are different from theirs.”

For now, the team only measured recombination within one small part of the fly genome—the section between the rough and ebony genes—and they don’t know if other sections are being shuffled to the same increased extent. They also haven’t shown that the extra shuffling leaves the new generation of flies in a better place when exposed to the same parasites. Do the larvae actually benefit? No one knows. “It does seem like a gap,” admits Schlenke.

It’s also unclear if the same effect exists in other animals, beyond fruit flies. What about us? Do human mothers give birth to children with more heavily shuffled genes after a bout of illness? “I wouldn’t be surprised either way,” says Schlenke. “It happens in plants and we’ve found it in fruit flies.”

Reference: Singh, Criscoe, Skolfield, Kohl, Keebaugh & Schlenke. 2015. Fruit flies diversify their offspring in response to parasite infection. Science http://dx.doi.org/10.1126/science.aab1768