Molecular Snapshots of the Past

By ROBERT HILL

In an Olin Hall laboratory, two of Ralph Bertrand's summer students gaze intently into lurid squares of translucent orange gel. The gel is lighted from beneath and its streaky glow looks like some synthetic dessert concoction. In fact, the garish color and Jello-like appearance of the medium seem to diminish its intellectual gravity. It is as exotic as it looks, striped with specimens of human DNA.

Bertrand, an associate professor of biology, hopes this research will hold clues for disciplines beyond the esoteric realm of molecular biology. These samples have been gathered from indigenous people now living along the probable migratory route of prehistoric populations, from the island of Taiwan to the American Southwest to Costa Rica. Admittedly, these sites on that purported map form a sketchy trajectory of human movement.

The gels contain DNA fragments of differing lengths collected from human blood and saliva. The difference in the lengths of the fragments is important, since it designates the presence or absence of Alu sequences in the chromosomal material. Basically, Bertrand and his students are looking at six different sites in the DNA of every individual sampled, sites where the Alu sequences will occur if they are present. "There is a stretch of DNA that occurs in all of us that either has a sequence inserted into it or it doesn't have that sequence," Bertrand explains. "We all have this region of DNA, either relatively small or containing a segment of DNA that makes it larger. We compare the frequency of these fragments, and that will tell us something about the relatedness of the individuals."

Alu sequences are nucleic acid placeholders within the DNA strand that do not necessarily determine genetic characteristics. So Alu sequences can change over time in the genetic makeup of populations without affecting individual development or survival of a population. What Bertrand looks for is the frequency of occurrence of these sequences within the samples from a particular population. The statistical frequency of occurrence gives him a "molecular picture" of the population over a range of such samples.

The next step is to check for statistical correspondences across more than one population, comparing these larger molecular portraits for, say, the Costa Rican and Taiwanese indigenes. Hence Bertrand and his students examine from six to nine completely different Alu sequences for each individual in the sample population, to establish some statistical accuracy. "We look at those numbers and try to generate a type based on frequencies," Bertrand says. "When we put these frequencies into a computer, they will label that population according to type. When we look at another comparable population, we can see how close the two are statistically."

The application to anthropological history is fairly simple: "We'd like to use the DNA to confirm historical migration patterns," says Bertrand. If sufficient statistical similarities can be established in the forensic evidence that Bertrand and his students have collected in samples from Navajo students in New Mexico, from a site in Costa Rica and from indigenous Taiwanese, then, suggests Bertrand, "These patterns suggest that people migrated from Africa across the Bering Strait, down through North America and eventually into South America. We've targeted regions along that route, trying to get as many samples as we can." Bertrand collects a minimum of 35 to 50 samples from each site to insure statistical accuracy. And to fill in the picture, he intends to gather samples from South America, Mexico, from other Southwestern tribes, and from Alaskan sites.

"We've been able to use college connections to gather the samples," he says. "For instance, we made our initial connections in Costa Rica through the ACM program there. Our latest connection in Asia was through the Asian Studies Program and the dance department. The connection I made with the Navajo people was through my own interaction with some of the high schools [in New Mexico]." Getting scientific samples from Costa Rica is notoriously difficult. Going around the scientific community enabled Bertrand to get the samples out -- a student, Rozelle Cawthorn '99, collected blood and literally carried the samples through customs. "We were going to send it Federal Express," says Bertrand. "One of the doctors he was working with suggested Rozelle just take it on the plane instead."

From mid-May to June, Bertrand was in mainland China making further connections to acquire samples. He visited universities in Taiwan and the mainland with an Asian studies group, and spent several days with a fellow researcher from Florida International University collecting samples in Taiwan. The college's reciprocal connection with Fudan University may eventually enable him to gather samples from Szechwan province, where 80 percent of the indigenous Chinese reside. The college connection has also helped Bertrand overcome local cultural suspicions of science and enabled research where better-connected scientists often meet resistance. "When a scientist approaches [indigenous people] they are most reluctant. I always take a cautious approach and try and give something back. With the Navajo, I agreed that I would come down with my son and spend two days teaching local high school teachers how to isolate DNA, going through the process with all the students in science classes. They isolated their own DNA, they visualized it, and we brought those samples home with us."

The students in Bertrand's lab this summer were science students working on a grant from the Howard Hughes Undergraduate Research Program. They are delighted at what Heidi Chang '00 regards as "a unique opportunity that wouldn't normally be afforded at such a small school. Undergraduates don't do this kind of research. Even when you do it later on, you're studying with a teaching assistant. It was great having a direct link with Ralph." The foray into molecular biology, she says, "taught us a lot of patience because it's more complex than what you would typically study as a science undergraduate." Their mentor was impressed with their enterprise in the lab. "Yesterday," says Bertrand, "I just handed them the DNA from Taiwan. They've taken off on their own. Once they've learned the technology, they pretty much understand exactly what's going on and are able to do it." They are also reading papers in anthropology as background for the scientific component.

And there is promise that this work in genetic anthropology may have some bearing on future research. The examination of indigenous populations is critical, says Bertrand, because "first of all, they'll help us trace these genetic relationships, and secondly because they're disappearing. But once we have cells from the blood, we're able to immortalize them with a virus so they'll never die. We can grow them up, freeze them, and at any time pull them out and reculture them." This frozen material may be important for future studies in genetics. Bertrand's colleague at Florida International University has started a repository of DNA specimens from indigenous peoples around the world.

Bertrand's scientific work on the genetic evidence for migration is bolstered by the academic interests of his Colorado College faculty colleagues. "There are other people here who are also interested in the relatedness of these [indigenous] people, but from a totally different perspective. When we were in Taiwan, for instance, Yun Yu Wang, who is a dance professor at CC, was more interested in looking at the cultural aspects of their dance and how it relates to Native American dance. She pointed out how certain chants and steps in the dances were very similar. When we visited one of these dance studios in a village, there was actually a totem pole that closely resembled a Native American totem pole.

"The unique thing about the college is that we can get these people together, " he adds. "There are lots of scientists around the world doing this kind of analysis. But they're not doing this all-inclusive analysis, taking the molecular evidence, the culture, the language and dance, the arts. We're able to see more than just molecules relating these people. There are actually many cultural similarities as well."

Photos by Sean Cayton '94

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