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Study of virus in fruit flies points to the repeatability of evolution

Tuesday, March 02, 2021

LAWRENCE — A new study in the journal eLife from researchers at the University of Kansas Department of Molecular Biosciences reveals that virus variants in fruit fly (Drosophila) populations separated by hundreds of miles have been evolving along a strikingly similar path.

“Drosophila is a 120-year-old model system for understanding all sorts of different things — genetics, in particular,” said co-author Robert Unckless, assistant professor of molecular biosciences. “The idea was that in each of these isolated populations, host-virus co-evolution can happen somewhat independently.”

Using rotten mushrooms, the KU investigators captured fruit flies (Drosophila innubila) in Arizona on three isolated “sky islands” — mountains that rise from the desert to form lush, isolated forest ecosystems. Then, they sequenced the genomes of hundreds of these individual fruit flies to confirm the populations were evolving with minimal-to-no gene flow between them.

“We collected flies from all these different populations,” Unckless said. “When you sequence a genome, you don’t just get the fly’s genome — you get the viral genome as well. By doing this, we get the genetic variation within the fly as well as the genetic variation within the virus. Here, it looks like we have three sky island populations where both the fly and the virus are evolving independently.”

Molecular analysis by Unckless and postdoctoral researcher Tom Hill suggested one of the strains of the Nudivirus (also called DiNV) in the fruit flies recurrently evolved at least four times in the past 30,000 years, three times in Arizona and once in another geographically distinct species.

“To me the thing that’s so striking is the fact that evolution repeats itself,” Unckless said. “The repeatability of evolution is all on the viruses’ side. The virus was able to recurrently evolve this high virulence — and it’s not one mutation, we’re talking about 11 mutations. And that’s fairly shocking.”

The analysis of DiNV in the fruit flies showed the mutations resulted in a viral variant that had a 100-times higher viral load (titer) in individuals. This high virulence type was also associated with higher population infection rates: the higher the proportion of infections caused by the high-titer type, the greater the overall population infection rate.

“If infected with this high-titer virus, the flies then were more likely to die — the high-type virus not only gives you more virus per fly, but it also is more virulent — it’s worse for them,” Unckless said.

The KU researchers wondered if they could replicate the results found on the sky islands in the lab by introducing the virus to uninfected fruit flies.

“We did do some experiments where we infected flies in the lab and showed not only can we recapitulate that result in the lab — flies infected with the high-titer type virus have about 100-fold higher viral titer than those infected with the low-titer type — and it’s about 100-fold, kind of remarkable that it was that similar,” the KU researcher said. “Also, the flies infected with the high-type virus died faster — and more of them died. This shows that the increased viral titer does cause increased virulence.”

A second fruit fly species from the Arizona sky island examined by Unckless and Hill, Drosophila azteca, was more commonly infected with a variant of DiNV that had a lower titer, or viral load.

“There’s a concept in epidemiology called ‘optimal virulence,’ and that can be different for the two different species,” Unckless said. “It could be that in Drosophila Azteca, the low titer variant actually does better and in Drosophila innubila the high titer variant does better — and all we’re really seeing in both species is the sort of spillover between species – the sloppiness of the virus transmission.”

Unckless said the fruit fly virus results seem to harken to a question about evolution posed by the famed American paleontologist Stephen Jay Gould.

“The idea is if you rewind the tape of life and let evolution go again, do you get the same result or you to get a different result?” Unckless said. “We can’t rewind the tape, but we can play the tape for three different populations in this study and we get more or less exactly the same thing for each of them.”

The findings someday could help guide understanding of viruses that infect humans, like HIV and COVID. For example, many of the variants in SARS-CoV-2 around the world are thought to be evolving using a similar blueprint – the same mutations arising in different geographic regions.

“Recently, colleagues of mine said, ‘Hey, this phenomenon that you just published on is happening now in coronavirus,’” Unckless said.

The National Institutes of Health supported this work.

Top photo: View of the Chiricahua Mountains near Portal, Arizona. Credit: Brandon Cooper.

Right photo: Collection site at the Southwest Research Station in Portal, Arizona. Using mushrooms, the KU investigators captured fruit flies (Drosophila innubila) in Arizona on three isolated “sky islands” — mountains that rise from the desert to form lush, isolated forest ecosystems. Credit: Brandon Cooper.