Evolutionary comparison finds new h...(es can be a gene coding for a string of ...)

Siepel and colleagues set out to find genes that have been "conserved" -- that are fundamental to all life and that have stayed the same, or nearly so, over millions of years of evolution.

The researchers started with "alignments" discovered by other workers -- stretches up to several thousand bases long that are mostly alike across two or more species. Using large-scale computer clusters, including an 850-node cluster at the Cornell Center for Advanced Computing, the researchers ran three different algorithms, or computing designs -- one of which Siepel created -- to compare these alignments between human, mouse, rat and chicken in various combinations.

Over millions of years, individual bases can be swapped -- C to G, T to A, for example -- by damage or miscopying. Changes that alter the structure of a protein can kill the organism or send it down a dead-end evolutionary path. But conserved genes contain only minor changes that leave the protein able to do its job. The computer looked for regions with those sorts of changes by creating a mathematical model of how the gene might have changed, then looking for matches to this model.

After eliminating predictions that matched already known genes, the researchers tested the remainder in the laboratory, proving that many of the genes could in fact be found in samples of human tissue and could code for proteins. The researchers were sometimes able to identify the proteins by comparison with databases of known proteins. The discovered genes mainly have to do with motor activity, cell adhesion, connective tissue and central nervous system development, functions that might be expected to be common to many different creatures.

The entire project, from building and testing the mathematical models to running final laboratory tests, took about three years, Siepel said. The work was supported by the National Cancer Inst
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