Research by an undergraduate at the University of South Carolina could lead to a better understanding of the genetic relationship among dinosaurs, birds and alligators.

Alex Vu thought he had understood DNA. The promising undergraduate at the University of South Carolina was using genetic fingerprinting to examine the evolutionary relationships of alligators when he realized he had not truly grasped the importance of DNA.

His epiphany came, he said, when he started using polymerase chain reaction technology and DNA sequencing to study the mitochondrial DNA of alligators. "I was taught about DNA in class since high school, but I never seemed to have understood how it worked." Only now, years after mastering countless tests on genetics, did it all click together. "I'm a visual learner," Vu said. "I finally saw DNA bands myself and understood how they were arranged."

Moreover, he saw the beauty in evolution, where slight variation a species doth make. "I realized how DNA can be very variable and very conserved at the same time. I finally understood how variations in DNA can lead to differences in species."

Vu's studies may eventually provide a better understanding of the relationship among dinosaurs, birds and alligators. His dream is to demonstrate through genetic analysis that birds and alligators share a common ancestor, a theory hotly debated by biologists.

Little was known about the mitochondria of alligators before Vu and his mentor at the university, Roger Sawyer, began their investigation. Sawyer, professor of biology and director of the HHMI undergraduate program at South Carolina, first met Vu when the Vietnamese-born, U.S.-raised student stayed at the campus for ten weeks during the summer through a separate Hughes grant for high schoolers interested in science. Vu was hooked during that first visit--"science became real," he said--and he entered the university the following year as an Honors College student.

As an undergraduate, Vu's second home was in Sawyer's lab, working up to 15 hours a week during school sessions and full-time during summers through the HHMI-funded program. "Alex had time to explore," Sawyer said. "He could keep focused and working without having to flip burgers to provide for an education. Students like Alex start growing on their own, and that's a pleasure to see."

Vu joined Sawyer's research program, hoping to help demonstrate the alligator's evolutionary relationship to the first birds. The conventional wisdom is that birds evolved directly from dinosaurs. Sawyer's group is using two lines of inquiry to probe whether crocodilians were part of this lineage.

First, the researchers analyzed beta-keratin, a common protein found in both alligator claws and bird feathers. By comparing the amino acid structure of keratin from alligators and chickens, they hope to show that the structural genes of bird feathers are also present in alligator claws. Such a finding would imply that the crocodilian lineage predated the development of birds. As Sawyer imagines it, the gnarly keratinized scales helped the earliest alligators avoid dehydration after emerging from the primordial soup. Sawyer speculates that eventually beta-keratin helped form claws, beaks and the strange lightweight scale known as the feather.

The second line of investigation, in which Vu played a key role, involved sequencing the alligator's mitochondrial genome. Wildlife officials in South Carolina provided Sawyer's lab with about 100 alligator eggs. Vu followed the alligators from embryo to hatchling, recording their growth and taking DNA samples of the animals' skin and blood.

Using DNA from the alligator hatchlings, Vu focused on genes that are not well conserved across species, and therefore are more likely to show genetic variation. The "D-loop"--the technical term for the area of the alligator mitochondrial genome analyzed by Vu and Sawyer--contains the initiation site for DNA replication in mitochondria. "There are certain parts of the D-loop that change a lot and other parts that are highly conserved," Vu explained. "So we compared these sequences with a bird's mitochondrial genome, which has been described, and we found differences."

Vu discovered that the location of genes surrounding the D-loop in alligators is different than it is in birds or in other vertebrates that have been studied. This evidence indicates that alligators and birds evolved differently. Sawyer's lab is currently analyzing the results and preparing a manuscript for publication. If accepted, the article would be Vu's first contribution to the scientific literature.

While the findings don't yet answer the pivotal chicken-and-egg (and alligator) question, they raise the possibility that ancient crocodilians did, indeed, give rise to birds. Regardless of where the evidence leads, the experience has solidified Vu's interest in research and made him eager to put his new scientific skills to use in helping future patients after he graduates from the Medical University of South Carolina, where he has just begun studies.