By Pat Harrison

During orientation for the Radcliffe fellows last September, Daven Presgraves RI ’09 learned that he was one of twenty scientists to be awarded a Lucile and David Packard Foundation Fellowship for Science and Engineering—but he told almost no one about it. A modest guy, he didn’t want to crow. “The Bush years were not kind to science,” he explains, “and the funding rates are abysmally low.” But of course he was—and is—thrilled that the Packard fellowship of $875,000 over five years will fund his ongoing research on the genetics of speciation, both at Harvard and when he returns to his home institution, the University of Rochester.

That September news was just the beginning of what Presgraves calls “the single most productive year of my career.” He was drawn to the Radcliffe Institute, where he holds the Grass Fellowship, partly because the effort to analyze the DNA sequence of the fruit fly Drosophila mauritiana is centered at Harvard. Information about mauritiana—in fact, all of the world’s fruit fly research—is archived in an on-line database called FlyBase, which is maintained by researchers at Harvard and Indiana University in the United States and at the University of Cambridge in the UK.

“Fruit flies have been the dominant genetic model for about a hundred years,” Presgraves explains. “The first evidence, for example, that genes were on chromosomes came from Drosophila.” In the late 1970s and 1980s, Christiane Nüsslein-Volhard and Eric Wieschaus used Drosophila as a model to open the field of developmental genetics, for which they won the Nobel Prize in Physiology or Medicine in 1995. (Nüsslein-Volhard delivered a Dean’s Lecture at Radcliffe in March 2008.)

Presgraves had used FlyBase before he came to Harvard (“Every Drosophilist uses FlyBase,” he says), but he is now participating in the sequencing of mauritiana. In the old days, sequencing a whole genome was a ten-year, hundred-person endeavor. Today, thanks to advances in sequencing and computing technology, Presgraves and two members of Harvard’s Department of Organismic and Evolutionary Biology (OEB) are performing this analysis themselves and anticipate that two major publications will result from their work by late 2009 or early 2010.

That was the second reason Presgraves wanted to come to the Radcliffe Institute—to collaborate with Harvard faculty members who work on the genetics of speciation. And last but not least, his girlfriend, Danielle Jones, was here, finishing her PhD in OEB, with a focus on theoretical population genetics.

During the first several months of his fellowship, Presgraves wrote a paper with his Rochester graduate student Shanwu Tang that was published in Science in early February. The paper was based on research about two other fruit fly species, Drosophila simulans, which hails from Madagascar, and Drosophila melanogaster, which lives in sub-Saharan Africa. As these flies were adapting to their environments, they accumulated changes in their DNA that caused the hybrid progeny of Drosophila melanogaster and simulans to die. Since each of the parent flies are viable, what caused the hybrids to die?

Presgraves and Tang identified two genes—the Nup160 (in 2003) and the Nup96 (more recently)—that have evolved rapidly in both species and are important in the death of hybrid flies. These two genes encode parts of a cellular machine called the nuclear pore complex, which controls the movement of molecules into and out of a nucleus.

“Shanwu and I were shocked,” says Presgraves. “Only half a dozen ‘speciation genes’ are known, so to find two of them that interact with one another as part of the same complex says that multiple parts of the same complex have evolved.”

The two genes may have evolved so quickly, he says, because they act as gatekeepers of a cell’s nucleus, a favorite target for viruses and selfish genes within the fly’s own genome. The Nup genes probably experience constant assault and therefore must constantly adapt. 

Presgraves is enthusiastic as he explains his research, at one point hopping up from his desk to draw a diagram on the whiteboard. “I love it,” he says, referring to his field. “I’ve been more successful than I could ever have hoped to be, including coming here.”

For someone who is not yet forty and says he wasn’t smart enough to become a physicist, Presgraves has already achieved a great deal, including the publication of almost thirty academic papers—six during his Radcliffe fellowship. After he received the Packard fellowship in September, additional honors came his way: an Alfred P. Sloan Foundation Fellowship and the Balfour Prize from the Genetics Society of the United Kingdom.

Oh, and there’s more. Presgraves got word in May that he’d been promoted with tenure at the University of Rochester, and Danielle Jones defended her thesis “with aplomb.” Then they went to Nantucket and got married.

Photo of fruit fly on blade of grass by Claude Nuridsany & Marie Perenno / Photo Researchers, Inc.; photo of Daven Presgraves by Tony Rinaldo; photo of Daven Presgraves and Danielle Jones by Cary Hazlegrove.