Gene found in fruit flies explains how one species evolved into two

Researchers have helped answer this question through the discovery of a gene responsible for dividing two species of fruit flies. The existence of this mysterious gene had been guessed at since 1910, when geneticists first noticed that the two types of flies, when mated, had only daughters -- and no sons. The definition of a species is that it cannot breed successfully with another species; understanding these reproductive barriers is key to understanding speciation.

The findings, published Friday in Science, arose from a collaboration of the laboratories of evolutionary biologist Dr. Harmit Malik, a member of the Basic Sciences Division at Fred Hutch, and fly geneticist Dr. Nitin Phadnis, assistant professor and Mario R. Capecchi Endowed Chair in Biology at the University of Utah.

Malik and Phadnis first met to brainstorm the experiment that would solve this evolutionary conundrum when Phadnis was a postdoctoral fellow in Malik's Fred Hutch lab. The researchers planned to mutate one of the fly species in the hopes of randomly disrupting the mystery gene and thus allowing males to be born.

Because they knew the flies would have many other mutations sprinkled throughout their genome, they calculated that they'd need to find seven rare male flies to conclusively pinpoint the mystery gene's identity. From that point, the scientists jokingly referred to the elusive sons as the seven samurai, after the classic Akira Kurosawa film of the same name.

The researchers estimated the seven samurai experiment would take about six months of mutating, mating and examining the tiny insects. Six months later, they'd found no male flies. About a year after that, however, after mating some 55,000 mother and mutant father pairs, the researchers sifted through 330,000 daughter flies and found six precious sons.

They never did find their seventh samurai, but it turned out they didn't need to. In collaboration with colleagues at the University of Washington, Malik and Phadnis found that all six males had mutations in the same gene, meaning they'd found what they were seeking.

Known as gfzf, this cell-cycle checkpoint gene is important for regulating how cells progress through division. For these particular fly species, Drosophila melanogaster and Drosophila simulans, it appears to also play a role in speciation -- how one species evolves into two.

The discovery that gfzf causes death or infertility in fruit fly hybrids "is really important in cancer biology," Phadnis said. "Cancer biologists are interested in cell cycle checkpoints because you can get cancer when those go bad [and cells proliferate uncontrolled]. Biologists want to understand the machinery. This work shows that some of those components in the cell-cycle policing machinery may be quickly changing."

Added Malik: "Cell-cycle policing by genes like gfzf plays important roles in correcting errors in the cell cycle that could result in cancers if left uncorrected. Our work suggests that speciation and cancer biology may be part of the same continuum of biological processes."

The problem of speciation has vexed evolutionary biologists for more than 100 years, but it's only with the advent of modern molecular tools that finding this gene was possible, Malik said.

"There was no way to use a traditional genetics approach. We needed a totally new, genomics-based approach to understand this," said Malik, also a Howard Hughes Medical Institute investigator. "So at the heart it's a genetics problem, but traditional genetics can't solve this problem."

Now that the researchers have figured out the solution to this single speciation event, they think their technique could be used to solve many other riddles of how species arise -- as long as those species are small enough to study by the tens or hundreds of thousands in the lab, Malik said.

This work was funded in the Malik Lab by grants from the National Institutes of Health, Howard Hughes Medical Institute and the G. Harold & Leila Y. Mathers Foundation.