A Novel Approach to DNA Analysis

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By looking at all 12 genomes, the team found that each type of functional element changes in characteristic ways over time, and those patterns of change serve as evolutionary signatures. For instance, a series of three-letter DNA sequences in which the first two letters are always conserved but the third one changes is likely to be a protein-coding gene, says Kellis. So the researchers designed computer algorithms to mine the sequence data and find the evolutionary signatures for each type of functional element. "This allowed us to find things that we would never have expected to find just by looking at a single genome," says Kellis.

Kellis's team found thousands of previously unidentified functional elements, including 150 protein-coding genes and more than a hundred microRNA genes. (MicroRNAs are short segments of RNA that silence genes by binding to specific sites in the genome.) The researchers also found that some genes, during their translation into proteins, ignore certain instructions and, as a result, acquire bits of protein encoded by other genes. "This is an entirely new mechanism," says Kellis, adding that his group has since found evidence of this mechanism in the human genome as well.

The second Nature paper describes research led by Andrew Clark, a population geneticist at Cornell University, who looked at known genes to see how they vary from one species to another and how they evolve, acquiring new functions as species adapt to their changing environments. Genes involved in the immune system, for instance, appear to evolve more rapidly than genes in the rest of the genome. The same was true for genes that regulate insecticide resistance.

Taste and smell receptor genes also undergo frequent changes. When the researchers compared species of flies that are generalists with those that have more specialized food preferences, they found that the specialists lose genes for different taste receptors at a much higher rate than the generalists do. "How you smell the world influences how you eat, and this will tell us an enormous amount about how genes that encode for smell and taste influence behavior," says Vosshall.

The studies of the 12 fruit-fly genomes will no doubt help scientists better understand the human genome, says Kellis. Not only do fruit flies and humans have so many genes in common, but now researchers have a systematic way of interpreting genomes that could lead to the discovery of entirely new kinds of functional elements, he says.