A ground-breaking comparative genomics study appeared online recently in the journal Genome Research. Led by Adam Siepel, graduate student in Dr. David Haussler's laboratory at the University of California, Santa Cruz, and the study describes the most comprehensive comparison of conserved DNA sequences in the genomes of vertebrates, insects, worms and yeast to date.

One of their major findings was that as organism complexity increases, so too does the proportion of conserved bases in the non-protein-coding (or "junk") DNA sequences. This underscores the importance of gene regulation in more complex species.

One of the most powerful approaches for pinpointing biologically relevant elements in genomic DNA is to identify sequences that are similar across multiple species. Such approaches are particularly useful for analyzing non-protein-coding sequences—sometimes called "junk" DNA. Although "junk" DNA is poorly understood, the increasing availability of whole-genome sequences is rapidly enhancing the ability of scientists to ascertain the biological significance of these non-protein-coding regions.

"Looking for functional elements in mammalian and other vertebrate genomes is like looking for needles in a haystack," said Siepel. "By focusing on conserved elements, you get a much smaller haystack. It's not guaranteed to have every needle in it, and not everything in it is a needle, but you're much more likely to find a needle if you look in this smaller haystack than if you look in the big one."

Siepel's team aligned whole-genome sequences for four groups of eukaryotic species (vertebrates, insects, worms, and yeast). The vertebrates included human, mouse, rat, chicken and pufferfish, and the insects included three species of fruit fly and one species of mosquito. Two worm species and seven yeast species rounded out the set.

For genomic scientists, the current study is a major contribution to the field. Not only will the new bioinformatics tool phastCons help researchers identify evolutionarily conserved DNA elements, the reported conserved elements are represented as conservation tracks in the widely used UCSC Genome Browser. "With phastCons and with the conservation tracks in the browser," says Siepel, "we're trying to make it as easy as possible for researchers to home in on functionally important DNA sequences."

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