Nitin Phadnis and Harmit Malik set out to conduct an experiment that could solve a century-old evolutionary puzzle: How did two related fruit fly species arise from one? Years after they began their quest, they finally have an answer.
The existence of a gene that helps make each of these fruit fly species unique and separate from each other had been guessed at since 1940, following experiments decades earlier in which geneticists first noticed that the two types of flies, when mated, had only daughters—no sons.
Scientists had previously discovered two other genes involved in driving the fruit fly species apart, but they knew those two genes weren’t the full story.
“One would think the genetics of speciation would be figured out given how long people have been trying to study this,” Phadnis says. “But it turns out that finding these genes is incredibly hard.”
Speciation is at the heart of evolutionary biology, a field of science focused on studying what processes have given rise to diverse species and traits. It occurs when two populations diverge to the point they can no longer produce fertile offspring. This process might be seen as a violation of Darwin’s paradigm that only genetic changes that increase a species’ overall fitness persist in groups of living creatures, Malik says. Darwin was so mystified by this process that he termed it the “mystery of mysteries.”
To identify the mysterious fly speciation gene, the scientists needed to devise a new strategy.
“There was no way to use a traditional genetics approach. We needed a totally new genomics-based approach to understand this,” Malik recalls.
Phadnis, then a postdoctoral fellow in Malik’s Fred Hutchinson Cancer Research Center lab who now leads his own research team at the University of Utah, sketched out the experiment. The researchers would mutate one of the fly species in the hopes of randomly disrupting the gene and thus allowing sons to be born. Then, they’d scan the genomes of the sons and parents to reveal the gene.
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, a name taken from the classic Akira Kurosawa film. Phadnis estimated the Seven Samurai experiment should take the team about half a year to complete.
But after 6 grueling months of mutating, mating and examining tiny insects, they’d found zero samurai flies. Phadnis and his geneticist colleagues can spot a lone male fruit fly among a sea of females by naked eye. They are shaped differently, and they have a dark pigmentation on their abdomen that the female flies lack, Phadnis says.
They pressed on. A year later, they had mated, in total, about 55,000 mother and mutant father pairs and sifted through 330,000 daughter flies. They had found just six sons.
Even though they never got their seventh samurai, they found what they were looking for.
“We got really lucky,” Malik says.
Each son had mutations in the same, single gene called gfzf, which regulates how cells progress through division—a process that often goes awry in cancer. By reducing the activity of the gene in mating fly parents, the researchers produced tens to hundreds of sons. The results were published in Science 
.
Gfzf joins a list of fewer than 10 known speciation genes across all animal species. It likely acts together with the two previously identified fly speciation genes.
The approach the researchers used could help scientists solve other puzzles of how new species arise—as long as those species are small enough to study in the tens or hundreds of thousands in the lab, says Malik.
It’s not clear yet how or why gfzf’s role in the cell cycle led to the division of species. This is one of the problems Phadnis and his newly formed laboratory team hope to tackle armed with a fresh grant from NIGMS. The fact that evolutionary biologists converged on the same types of genes that have been of interest to cancer biologists for decades suggests that resolving one “mystery of mysteries” might hold answers for mysteries in other fields of biology.
This work was funded in part by NIH under grants R01GM074108, R01GM115914 and R01HG006283.
Content adapted from a Hutch News story.
About Rachel Tompa
This post was contributed by Rachel Tompa, a science writer at the Fred Hutchinson Cancer Research Center. Reach her by email at rtompa@fredhutch.org or follow her on Twitter at @Rachel_Tompa .