Planos mestres

segunda-feira, agosto 17, 2009

The New Scientist
Volume 23 | Issue 8 | Page 44

By Karen Hopkin

Master Plans

Sean Carroll earned his celebrity by stitching together the patterning that underlies much of the animal kingdom’s various shades and shapes.

Sean Carroll’s most flamboyant finding was prompted by an innocent query before a seminar. Carroll had gone down to Duke University to give a talk about his research on the genes and molecules that direct the regular spacing of bristles on a fruit fly leg. There he met up with Fred Nijhout, who had been studying the spots on butterfly wings. “Fred asked, ‘Do you think the things you’re working on could explain these patterns, too?’ And he shows me a bunch of butterflies,” says Carroll. “I said, ‘I don’t know, Fred. It’s a big question.’ But it haunted me.”

So Carroll asked Nijhout for some butterflies. And he set out to do the same sort of rigorous analysis he’d been conducting on Drosophila. “This was in the early days—1991,” he says. “So there were no genomic resources. Just old fashioned molecular biology.” His team isolated the butterfly counterparts of all the fruit fly genes that govern the formation of legs and wings. They then did in-situ hybridization—staining developing butterfly wings with probes that would locate the genes’ RNA transcripts—to see whether and where the genes were expressed. “It was work. It took time. And there was no guarantee of an interesting payoff,” he says. “But our good deeds were rewarded and we did get the interesting payoff.”

First, they found that the same genes that make a wing in a fruit fly also make a wing in a butterfly. “So we saw that these genes have deeply conserved jobs in building limbs,” says Carroll. But the big surprise came next. To address Nijhout’s original question about spots, Carroll and company then looked to see which genes are turned on in a butterfly chrysalis a week or so before it emerges to unfurl its colorful wings. And they discovered, much to their surprise, that one of the master genes involved in making limbs, a gene called Distal-less, is also switched on in the center of every developing eyespot, one of the wing’s most dramatic markings.

“It just smacked us in the face,” says Carroll. “Here was this ancient gene, doing something entirely new.” In addition to its regular duty assembling the wing, it also graced the wing with spots. “So the message,” says Carroll, “is that you can teach old genes new tricks.”

And as an HHMI investigator at the University of Wisconsin, Madison, Carroll has shown again and again that much of the physical and anatomical diversity we see in the creatures around us is generated using the same genes—and their associated regulatory networks—in novel ways. What’s more, he’s found that when evolution tinkers with animal form, it often does so by tweaking the switches that control gene expression.

“Sean got a lot of notoriety for showing that the same genes involved in the patterning of limbs were co-opted to give the patterns on butterfly wings,” says Cliff Tabin of Harvard Medical School. The study made the cover of Science in 1994 and was picked up by the New York Times. “But regardless of popularization,” says Tabin, “Sean is without a doubt one of the leading people in pattern formation during embryonic development and in evolution—and he has been a true pioneer in bringing those fields together.”

“He’s really been at the forefront of figuring out the genetic and molecular changes that have led to morphological diversity,” adds Jim Skeath of Washington University School of Medicine, a former student. And he’s written eloquently about the topic in textbooks and books aimed at the general public. Carroll’s work—and his words—“have changed the way we think about how bodies evolve,” says Neil Shubin of the University of Chicago.

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