A Stomach-Churning Genome

Researchers around the world are about to get their first detailed look at the genetic blueprint of a pathogenic microbe that causes most peptic ulcers. In tomorrow's issue of Nature, a team of scientists from The Institute for Genomic Research (TIGR) in Rockville, Maryland, will publish the complete genetic sequence of the bacterium Helicobacter pylori, spelling out the precise molecular composition of the organism's genes.

The availability of the H. pylori sequence is "great news," says computational biologist Eugene Koonin from the National Center for Biotechnology Information in Bethesda, Maryland. "It's important to have the genome to find a vaccine" and develop specialized antibiotics, says molecular geneticist Antoine Danchin of the Pasteur Institute in Paris.

To figure out the genetic codes of H. pylori, TIGR researchers fell back on a strategy they have used before. They first broke the organism's genome into pieces, sequenced each piece, and then used powerful computers to help them arrange the sequenced pieces in the correct order. Among the 1.6 million base pairs in H. pylori's circular chromosome are some 1590 genes, many of which code for molecules that help the bacterium colonize the human stomach, reports TIGR molecular biologist Jean-François Tomb. He and his colleagues also find that this microbe has a section of DNA in which some of the base pairs that make up the letters of the genetic code are repeated. Those repeats often lead to slight changes in the proteins coded for by that DNA, changes that enable bacteria to evade recognition by the human immune system, say Tomb and his colleagues.

This is the fifth bacterial genome to be completely sequenced and the fourth determined by TIGR. It's not the first time researchers have sequenced this particular organism, however. In December 1994, Genome Therapeutics Corp. in Waltham, Massachusetts, announced that it had sequenced a different strain of H. pylori. Those data were never made public, but were provided to the Swedish pharmaceutical company Astra AB as part of a $22 million, multiyear agreement. Now, TIGR is not only publishing the sequence, it has also made the sequence available on the World Wide Web at www.tigr.org/tdb/mdb/mdb.html.

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