Bacterial genomes sequenced.

Imagine taking a bundle of identical French newspapers and cutting them into thousands of random sentence fragments. To reconstruct a single copy of the paper in English, one could translate the fragments and then, by matching up the overlapping phrases between them, reassemble the text.

That's the essence of a method some researchers are using to spell out the complete DNA sequence of organisms. With that strategy, researchers announce, they have for the first time deciphered the entire genome of a free-living organism, the bacterium Hemophilus influenza. (Viruses, a number of which have been sequenced, can't live without the DNA of a host organism.)

Francis S. Collins, director of the National Center for Human Genome Research, hails the effort as a "significant milestone" on the road to sequencing the much larger human genome.

The H. influenza work stems from a collaboration led by Hamilton O. Smith of Johns Hopkins University Medical School in Baltimore, who won a Nobel prize for isolating H. influenza enzymes useful in biotechnology, and J. Craig Venter, who heads the Institute for Genomic Research in Gaithersburg, Md.

The two groups chopped up DNA from many H. influenza bacteria, creating short spans of genetic material from which they could identify individual base pairs, the chemical units that make up DNA. From these sequenced fragments, they reassembled one genome representing the bacterium.

H. influenza's genome apparently packages 1,830,121 base pairs into some 1,749 genes, says Venter. As expected, the bacterium's genome is considerably larger than that of viruses, a number of which have been sequenced.

"It's going to take us months, if not years, of looking at this data to truly understand it," comments Venter.

Already, however, he and his colleagues have picked out known families of genes within the genome and have discovered others whose functions are a mystery.

With the experience of H. influenza to guide them, says Venter, it took his group only a few months to sequence the 500,000 or so base pairs of Mycoplasma genitalium, a simpler bacterium. He notes that a laboratory with equipment similar to his might sequence 10 or more microbial genomes a year.

"The door to comparative evolution and functional genome analysis is open, and the first steps have been taken through it," says American Society for Microbiology President David Schlessinger of Washington University in St. Louis.