Insects show Sean Carroll how to spot evolutionary change
By Steve Mirsky
When collecting butterflies is your job, what do you do for a hobby? Biologist Sean Carroll leaves his butterflies in his lab and hits the road in search of bigger game. "I like to go to jungles and swamps and coral reefs," he says of trips with his wife Jamie and some percentage of their four sons, Josh, Chris, Patrick, and Will. "I love wildlife and I love to travel." He also has what he calls "paleontologist envy," which takes him out of his lab, home to his studies of butterfly and fruit fly genetics, and off to find fossils in far-flung places. From fossils to butterflies, however, Carroll is actually always looking at the same thing: how evolution has come up with the seemingly endless forms of life on earth.
In fact, Endless Forms Most Beautiful is the name of a recent book by Carroll, an HHMI investigator and professor of genetics and molecular biology at the University of Wisconsin-Madison. The title comes from the last line of the 1859 book by Charles Darwin that transformed the entire field of biology, The Origin of Species: "There is grandeur in this view of life, with its several powers, having been originally breathed by the Creator into a few forms or into one; and that, whilst this planet has gone cycling on according to the fixed law of gravity, from so simple a beginning endless forms most beautiful and most wonderful have been, and are being evolved."
Standing an even six feet tall, Carroll has the reddish brown hair and beard common to his Celtic ancestors. "I blend in in Ireland very well," he notes. He also serves as an adviser to the Science Foundation of Ireland. Did the foundation invite him because he's a biologist named Sean? "I actually asked exactly that question of the molecular biologist in Ireland who recruited me," Carroll laughs. "He said, 'Well, there are qualifications beyond those-but we figured you'd be sympathetic!'"
The Carroll laboratory is home to butterflies and thousands of fruit flies, representing some 30 Drosophila species, as well as to a dozen or so graduate students and postdoctoral fellows at any time, not to mention an undergraduate or two. Carroll even has the occasional eighth-grader working in the lab for a semester as part of a mentorship program with one of the local middle schools. "You usually try to get their hands dirty doing something fun and interesting," he says. "And almost anything with DNA thrills kids."
The lab lights are on almost constantly. Many lab members work weekends and late into the night, surrounded by fossils, images of butterflies, and microscope images of animal embryonic development. "They're highly motivated and very independent," he says of his group. "They've developed a lot of independent collaborations across the lab. I see myself as a player-coach of a team of very talented individuals. My job is to facilitate their efforts-and try to get into the game every now and then."
Carroll, now 45, was born and raised in Toledo, Ohio, a city probably best know as the hometown of Corporal Klinger on the TV show M*A*S*H. Played by actor Jamie Farr, a real-life Toledoan, Klinger often waxed rhapsodic about Toledo and the local minor league baseball team, the Mud Hens.
"Actually, it's all true," Carroll says. "Farr was a classmate of a friend's dad, and I went to Mud Hen games all the time." He also remembers playing baseball 12 hours a day in the summer. Of course, Toledo had high culture, too-it was home to the Gregorian Institute of America, devoted to the study and performance of Gregorian chants, the principle music used in church services in the first thousand years of Christianity. Carroll's father was a Gregorian chant expert who settled in Toledo to work at the institute.
Biology early on became music to Sean's ears. "As a kid I liked animals and dreaming of faraway places. And I liked the TV show Wild Kingdom and reading National Geographic magazine. They took me to these fantastic places, like the African savanna and the barrier reefs. The living world just seemed so interesting."
His academic biology career began with research into the inner workings of that living world. After college at Washington University in St. Louis, Carroll went to Tufts University School of Medicine in Boston for a doctorate, planning on studying immunology. While there, he found that development-how a single fertilized egg cell becomes an adult organism with eyes and arms or wings-was of greater interest, especially when he considered development for its connection to evolution.
During this period in the early 1980s, the biology community was beginning to grasp the fact that wildly different organisms shared many of the same important genes. This realization was a surprise to most researchers, causing an evolution revolution. As Carroll points out in Endless Forms Most Beautiful, one of the greatest evolutionary biologists of the 20th century, Ernst Mayr, wrote that "the search for homologous genes [genes in different species that nevertheless share a high percentage of their DNA sequences] is quite futile except in very close relatives." But the data on gene structure made available in the last 30 years shows that many crucial genes have been passed down almost unchanged for hundreds of millions of years. Species that are only distantly related therefore have many homologous genes because the original genes existed in a common ancestor. Even organisms as different as humans and yeast share many genes involved in basic biochemical pathways. And we know today that humans and chimpanzees share about 98 percent of their genes.
But genes don't just sit there. They get turned on and off, so that their protein products get made at specific times and places. Proper development depends on the right genes being active at the right times. Later in the 1980s, biologists began to realize that gene-dependent changes in development were behind evolutionary changes in form. Organisms that had almost identical genomes could still appear quite different because their developmental programs were quite different. Carroll was a leader in this new discipline, dubbed evo devo, short for evolutionary developmental biology. Evo devo explores the details of how alterations in developmental programs contribute to evolutionary change.
Addressing big questions, such as how evolution works, is a major challenge for a scientist. One way to get meaningful answers is to find specific, smaller questions that nevertheless have widespread implications. For Carroll, important clues to evolution's secrets lie in butterfly and fruit fly wings.
Over evolutionary time, the same genes can be recruited to perform different jobs in different species. For example, in the early 1990s, Carroll and his laboratory team found that a well-known gene called distalless, crucial for the proper growth of fruit fly limbs, had an additional responsibility in butterflies-making wing spots. "Diversity of form evolved through changes in development," Carroll explains. "You have to understand development, and then you have to pinpoint those moments and places when development diverges between species or between higher orders." Two closely related species of fruit flies might make different decisions about wing patterning only in the very last few hours of development. "That's why the link between evolution and development is so intimate," Carroll says.
Much of the work in Carroll's lab today still involves seeing spots-on the wings of fruit flies. "What could be simpler than a black spot on a wing," he asks. Tiny fruit flies might look indistinguishable to us, but the members of different species can look quite different to a trained researcher using a microscope. Wing spots play a part in some courtship rituals, so they're important. And some species that today do not have spots clearly had ancestors that did have spots. Understanding the when, where, and why of the coming and going of spots should therefore provide basic evolutionary insights.
"I'm going to study wing patterns in fruit flies," Carroll says, "but the principles we're going to uncover probably apply to body patterning throughout the animal kingdom. And some of the deep molecular mechanisms probably apply to evolution in general." Darwin gained some of his fundamental insights into evolution by studying pigeon breeding. "Fruit fly spots are my pigeons," Carroll says, "in terms of understanding, at the deepest level, how new features evolved." Prominent geneticist Cliff Tabin of the Harvard Medical School notes, "Sean's comparative work examining the molecular control of pigmentation patterns in related Drosophilids [fruit flies of different species] has set the standard for investigations into the genetic bases of morphological evolution."
English poet John Keats thought that Isaac Newton had "destroyed the poetry of the rainbow" by explaining its physics. When Carroll's butterfly work was a brief media sensation, a television essayist had a similar notion. "He started talking about how scientists have figured out how colors appear on butterfly wings," Carroll recalls, "and that it raised the question of whether we really wanted to understand the beauty of nature. My answer: Yes! It's a blast! And don't worry-there will always be more left to try to understand."
Sean Carroll's research
Fruit fly as a model organism
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