A Novel Approach to DNA Analysis

Comparing fruit flies reveals a new way to identify the functional elements of genomes.

In a milestone for the emerging field of comparative genomics, an international team of scientists has carried out a comparative analysis of the genome sequences of 12 different species of fruit flies. Not only did the researchers uncover patterns in the way that genes evolve as species adapt to different environments, but they also developed a new way of identifying the functional elements of the genome--a discovery with potentially far-reaching consequences.

Cheaper by the dozen: This species of fruit fly, called Drosophila ananassae, is one of 12 species whose genomes were recently sequenced and compared in one of the largest efforts in comparative genomics to date. Credit: Image of D. ananassae by Sergio Castrezana and Terry Markow, Tuscon Drosophila Stock Center, University of Arizona. Reprinted with permission of the Genetics Society of America.

For more than a hundred years, the fruit-fly species Drosophila melanogaster has been instrumental in the study of genetics, developmental biology, and animal behavior. Because a significant number of human genes have fruit-fly analogues, researchers have also used the insect to study many human diseases, including cancer, diabetes, and neurodegenerative disorders such as Alzheimer's. In 2000, scientists published the genome sequence for D. melanogaster; the sequence of a second fruit-fly species followed several years later.

There are 1,500 species of fruit flies, however, and they vary in appearance, behavior, and habitat. To fully understand the fruit-fly genome and how it has evolved, a consortium of more than a hundred labs around the world sequenced an additional 10 species and compared all 12 sequences. The group details its findings in two reports published in the November 8 issue of Nature.

"If you want to get a crystal-clear picture of how genes influence what an animal will look like, what it will eat, what behavior it will exhibit, this is a completely unparalleled resource for doing that," says Leslie Vosshall, a neurogeneticist at Rockefeller University, in New York.

The researchers selected species from all over the world--from Africa, Asia, the Americas, and the Pacific Islands. Some species are widespread and feed on a range of foods, whereas others are more limited. For instance, one species lives only on the Seychelles islands off the east coast of Africa and eats only one kind of fruit.

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In one of the papers, a team led by Manolis Kellis, a computational biologist at MIT, compared the 12 sequences in order to identify all the functional elements in the fruit-fly genome. These include not only genes that code for proteins, but also sequences that help regulate gene expression by, for instance, encoding small RNA molecules that bind to other parts of the genome. To find these elements, researchers typically look for sequences that are common, and therefore highly conserved, among different genomes. "The basic premise of comparative genomics is that if something is conserved over millions of years in a dozen species, it's likely to do something useful," says Kellis.

But Kellis and his colleagues were also seeking an alternative strategy. They figured that by looking only for sequences that have remained roughly the same, they would miss a large number of functional elements. For instance, protein-coding genes can undergo extensive changes and yet retain their critical functions.