Mutations to a cholesterol-metabolism gene are responsible for restricting one species of fruit fly to life on a particularly rare cactus, according to a report in Science, out today (September 27). But despite causing this loss in diet diversity, the mutations were under positive selection and appear to provide flies with a fitness advantage.

“One generally thinks of things that drive evolution as things that would expand the niche, whereas this is actually restricting it,” said Michael O’Connor, a fruit fly biologist at the University of Minnesota, who was not involved in the study. “That seems very curious.”

Indeed, the new study on the fruit fly species Drosophila pachea stands in stark contrast to the generally held belief that loss of a metabolic activity happens by chance rather than being selected for, explained Virginie Orgogozo, an evolutionary biologist at the Institut Jacques Monod in Paris, France. Orgogozo and...

A few years ago, researchers discovered the enzyme responsible for converting cholesterol to 7DHC. It was named Neverland because flies that lacked the protein never transitioned from larvae to adults. Orgogozo knew immediately that Neverland would be a great starting point to look for differences in D. pachea. “I was really expecting a loss of function or that there would be no gene,” she said. But Neverland was present in D. pachea and displayed a pattern and level of expression similar to that in other fruit flies. “This was the first surprise,” said Orgogozo.

DNA sequencing did reveal several amino acid differences in the D. pachea Neverland protein, however. And, subsequent functional assays revealed that four of these differences were responsible for the loss of its cholesterol-converting ability. D. pachea’s version of Neverland was instead capable of making 7DHC from lathosterol—a rare sterol made in senita cacti.

Then came another surprise: the Neverland enzymes from other species were capable of utilizing lathosterol too. Not only that, the other species’ enzymes were better at it. The four amino acid mutations in D. pachea had thus also impaired an ancestral lathosterol-converting capability. “This was very strange,” said Orgogozo.

Complicating matters further, a sequence analysis indicated the mutations in D. pachea’s Neverland exhibited low sequence diversity between individuals, suggesting that the gene had undergone positive selection.  “When you have a new mutation arising in a population, it will spread rapidly if it has any advantage, so there is no time to accumulate new mutations,” Orgogozo explained.

Studies in live flies confirmed this positive-selection prediction. Replacing the Neverland protein of D. melanogaster with that from D. pachea conferred a significant fitness advantage. More of the recipient D. melanogaster larvae made it to adulthood—when fed on a lathosterol-containing diet—than did wildtype D. melanogaster fed their normal cholesterol-containing diet.

“We always think an enzyme has to be the best possible, but maybe for the organism it is better to have an enzyme which is not so efficient,” Orgogozo said, suggesting that perhaps a slower enzyme might prevent the hormone being created at the wrong time or place.

Whatever the reason for the fitness advantage, the mutations to D. pachea’s Neverland might be a double-edged sword, said Stephen Schaeffer, a molecular population geneticist at the Pennsylvania State University, who did not participate in the research. “It’s an advantage right now because it doesn’t have competition from other fly species”—not only does the senita cactus not produce cholesterol, it also has toxins to which only D. pachea is resistant—“but it’s not unheard of for habitats to be destroyed. If this cactus disappeared, this fly would be in bad shape,” Schaeffer said.


M. Lang et al., “Mutations in the Neverland gene turned Drosophila pachea into an obligate specialist species,” Science, doi: 10.1126/science.1224829, 2012.

Interested in reading more?

Become a Member of

Receive full access to more than 35 years of archives, as well as TS Digest, digital editions of The Scientist, feature stories, and much more!
Already a member?