The Engineer, the Rat, and the Fruit Fly
by David Pescovitz
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Anat Caspi helped sequence the genome of the laboratory rat, only the third vertebrate whose genome has been deciphered. (courtesy NHGRI)
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Engineering student Anat Caspi has an intimate relationship with rats, mice, and flies. She listens to their deepest secrets and poses an unending number of questions about their pasts. Caspi is not as odd as she sounds though. A member of the Bioengineering Graduate Group, Caspi uses novel computer software to unravel the evolutionary mysteries of lab rats, mice, fruit flies, and humans.
"The real crux of the research I contribute to is to provide a detailed window not only into the evolution of rodents and flies but evolutionary and genomic processes in general," says Caspi, a graduate student of mathematics professor Lior Pachter.
In March, Caspi was one of more than 200 co-authors of a monumental collection of scientific publications outlining the genome of the common laboratory rat. It was only the third mammalian genome to be sequenced, following the mouse and the human. The ability to read and compare the genomes and evolution of rats, mice, and flies sheds light on our own genetic make-up. Armed with data from these various animal sequences, researchers will be better able to develop new weapons in the battle against human disease. The rat is of particular interest because it's commonly used in biomedical research and drug development.
The research was a massive collaboration that included a team led by Pachter and groups from Stanford University , UC Santa Cruz, and Pennsylvania State University. Three other Berkeley engineering students--Colin Dewery and Sourav Chatterji, graduate students in the Department of Electrical Engineering and Computer Sciences, and undergrad Kushal Chakrabarti--were also co-authors on the papers published in the journals Nature and Genome Research.
"The sequencing of the rat genome constitutes another major milestone in our effort to expand our knowledge of the human genome," said Francis S. Collins, director of the National Human Genome Research Institute. "As we build upon the foundation laid by the Human Genome Project, it's become clear that comparing the human genome with those of other organisms is the most powerful tool available to understand the complex genomic components involved in human health and disease."
In both the rat effort and the ongoing Berkeley Drosophila Genome Project, Caspi focuses on computationally comparing laundry lists of the animals' genes to identify transposons, known as "jumping genes." These segments of DNA can literally hop from one location in the genome to another, commonly causing mutations. For example, transposons are what enable bacteria to mutate and become resistant to drugs.
"We'd really like to understand more about the mechanism that causes these mutations to occur," Caspi says.
In the case of the rat, Pachter's laboratory was provided with a rough draft of the sequence. They then used software they had developed to align the rat genome with that of the previously-sequenced mouse and human. Once aligned, Caspi and her colleagues can generate computer models and sift through the data for similarities and differences, including transposons that are common between the animals.
"The comparative genomic techniques help us identify the elements of a genome that have been conserved by evolution as well as what has changed," Caspi says.
According to the Nature paper, most human genes associated with diseases also have counterparts in rats. Meanwhile, the data also revealed that 40 percent of the genome of rats, humans, and mice is inherited from a common mammalian ancestor.
As more genomes are sequenced, Caspi hopes to improve genetic models to include events such as transposition and other mechanisms leading to mutations. For example, plants and viruses, she says, exhibit many genomic events that scientists are only beginning to uncover.
"Understanding the processes that plants and viruses undergo when they evolve would be a big jump in agricultural and pharmaceutical development," she says.
Berkeley Comparative Genomics
Lior Pachter's Home Page
Berkeley Drosophila Genome Project
"Mathematicians, computer scientists play key role in analysis of lab rat genome" by Robert Sanders (Media Relations, 31 March 2004)
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