Evolution: Toledo Native's 'Evo-Devo' Research Reshapes the Field

Jul 02, 10:42 AM

Current Headlines: By Jenni Laidman, The Blade, Toledo, Ohio

Jul. 2--He spent his summers playing ball, 12 hours a day he and the other guys on Berwick Avenue pursued the sport with tireless passion.

They played until the streetlights came on. They played until someone's mom called from an open screen door, and then they kept playing as the door slapped behind her. They played until she called a couple of more times. They played until they could not play any more.

Still, Sean Carroll didn't end up playing baseball for a living. One of his buddies, John Locasio, was drafted by the Reds. Mr. Carroll hadn't gotten a bat on one of John Locasio's pitches since 7th grade.

But he didn't do too bad for himself anyway.

"Of all the scientists in the world today," wrote philosopher of science Michael Ruse, "there is no one with whom Charles Darwin would rather spend an evening than Sean Carroll."

Almost as good as baseball.

Mr. Carroll, a graduate of St. Francis de Sales High School -- where he cracked open a beer at the end of his graduation speech to toast the audience (it was the 1970s, after all) -- is an eminent researcher in a new field of biology called Evo-Devo. Not only has his research been essential to the field's advance, his writing -- three books so far -- may make him the most prominent explainer of this marriage of evolutionary and developmental biology. This year, his research won him election to the prestigious National Academy of Sciences.

If the son of Joan and the late J. Robert Carroll were to draw a line from boyhood pursuit to scientific career, it wouldn't start at baseball. It begins instead in the fields around Maumee Valley Country Day School. That's where the youngest Carroll child developed a fascination for snakes. The hunt for them. The collection of them. The admiration of the stripes and splotches that marked them as slithering art.

"I really liked the patterns, the color patterns of snakes, the fur patterns on mammals," he said.

Now maybe that's an adult's post-hoc analysis. But it fits: Now his life is absorbed with patterns, not the pattern of snake skin -- although butterfly wing patterns have won him considerable notice -- but the patterns of embryonic development, the patterns of genes switching on and off, the patterns imposed on a fruit fly embryo.

Before Evo-Devo, indeed, ever since "The Origin of the Species" was published in 1859, science understood that it was mutation and natural selection that drove the engine of evolution, a process Mr. Carroll calls "error and trial." First, nature makes a mistake, then nature tests the error to see how it works out. Occasionally, a mistake passes the test by contributing to the improved survival, and in a series of such step-wise changes, a species changes.

But how could such a thing happen? Not long after scientists knew that the mutations Darwin posited took place in genes, it also knew mutations were often bad for the organism. Repeat a pattern too often on Chromosome 4, and you have Huntington's disease. Make a little mistake on chromosome 7, and cystic fibrosis could result. In fact, as researchers crawled across the genome, genes got earned their reputation by the trouble they caused. BRCA 2 and BRCA 3 won fame as breast cancer genes. A gene called apoE4 is associated with early-onset Alzheimer's disease.

So how could evolution result from mutations?

We'll get to that, but first, it's important to understand some similarities, between, say, a chubby baby girl with big brown eyes and a fruit fly with weird compound eyes. Certainly the differences are obvious and profound. Talking about a common ancestry seems like an idea one would find in a not-quite-plausible science fiction thriller.

But evolution says we are family, at least way, way back in evolution: baby girls, fruit flies, pond scum, chimpanzees.

Group hug, brothers and sisters!

While researchers accepted the Darwinian proposition of billions of years of mutation creating the bushy divergence of species that made us us, and fruit flies fruit flies, they never expected genes to reveal the evidence of the tree trunk from which those branches grew. Too much time had passed. Too many differences accumulated. Simply compare aforementioned baby girl with a fruit fly. She has two legs. It has six. It has antenna. She doesn't. She lacks wings. It has two.

What could be similar?

Still, folks studying the development of embryos uncovered deep similarities untouched, or touched only lightly, by the many millennia of evolution.

"The conventional wisdom was fruit flies and furry animals would have nothing in common," Mr. Carroll said. "That was shattered. The degree to which they had things in common was absolutely stunning. No biologist on the planet predicted it."

The similarities were revealed most often in a groups of genes Mr. Carroll refers to as the "genetic tool kit."

A lot of this scientific discovery was going on when Mr. Carroll was still in college. As researchers worked with these tool kit genes, they learned that even the way the genes lined up in the genome was important. If a gene was moved from its middle position to the front position, scientists could create things like fruit flies with legs where there antenna should be.

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Mr. Carroll joined the exploration when he signed on with Matthew Scott at the University of Colorado at Boulder.

"Matt had isolated some of these spectacular body-building genes from the fruit fly," Mr. Carroll said. "These genes ended up being a passport to the whole kingdom."

But as anyone who's ever gone through airport security knows, a passport is no guarantee of instant entry.

"For 18 months in Colorado I didn't have a single data point worth mentioning," Mr. Carroll said.

Mr. Carroll writes about the moment when his work finally paid off in his book, Endless Forms Most Beautiful: The New Science of Evo Devo, published in 2005.

"It's very late on a spring night in Colorado. The lab is dead quiet. I'm repeating a procedure for the umpteenth time in the past 18 months. ... I am getting nervous. ... I know this is probably the last shot we have. I can't think of any more ways to do this experiment. ... I'm stuck with nothing to show for a year and a half's work."

Then he puts his newest group of fly embryos under blue light. Green stripes glow from the tiny embryos.

This is the "Ah ha!" moment. Those green stripes marked where a gene turned on inside the embryo, proof he had found a way to tail the genes as they worked during embryonic development.

"Sean has always had the ability to think way ahead and frame good questions and the corresponding good experiments to answer them," said Mr. Scott, now at Stanford University. "He conceives of a study at a very early stage better than most people do."

Where Mr. Carroll's contribution really took off is when he shifted from looking at the deep similarities in tool kit genes, and focused instead on the differences in embryonic development from species to species: essentially the "how" of evolution.

He picked butterflies to tell the story in his laboratory at the Howard Hughes Medical Institute and Laboratory of Molecular Biology at the University of Wisconsin, where he had moved in 1990.

"The wings were such obvious models of diversity," he said. "My lab had been working on how insect wings developed for several years. We made a foundation studying fruit flies."

They found not only the same genes working in butterfly development, but ultimately, learned why those identical genes worked in a butterfly with such dramatically different results than they had in a fruit fly.

First, they learned that a gene that draw eyes on butterfly wings -- an adaptation that may serve to startle predators by creating a threatening face where a butterfly used to be -- is an ancient gene used for hundreds of millions of years to make limbs. Then his lab found that the gene that made the big hind wing in a butterfly was the same gene responsible for the tiny hind wing of the fruit fly.

Examination of numerous species showed nearly identical genes producing completely different results, from wing spots, to legs, to spider lungs.

In the early 1990s, Mr. Carroll said, he gave a talk on some of this work to a group of scientists in Edinburgh, Scotland.

"It's the closest I can say to a crowd going wild for pure data. No one had seen anything like it," he said.

And this is the "how" part of the story. What was different was not the gene, but the DNA sequence that told the genes when to turn on and turn off. By 1995 he was convinced that what evolved from species to species was not the tool kit gene, but the many switches, sometimes more than one hundred switches, that dictated its operation.

There is evidence that genes can also evolve, but the switches "are hot spots for evolution. They fine tune body patterns," Mr. Carroll said.

In 2005 and 2006, publications from his Wisconsin laboratory were demonstrating the power of switches, and mutations in switches, to change the on-off pattern of genes.

"The rules that apply to snakes and birds and frogs and mice and butterflies and lobsters, one would fully expect those exact same rules to apply to us," Mr. Carroll said.

But the question is humans is harder to answer. One can study fruit fly genetics by messing with the genome of the developing fruit fly. You can't do those experiments in humans. Other methods will be required.

But Mr. Carroll anticipates that human evolution will bear the same hallmarks:

"The similarity of the genetic tool kit is frighteningly clear when you look at the chimpanzee verses the human genome," he said. The differences between the two primate species will likely arise from the same genetic mechanism used in other living things.

"A lot of changes are taking place in genetic switches," he said. "That's where the smoking gun is."

Contact Jenni Laidman at:

jenni@theblade.com or 419-724-6507.

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