Complete genome sequences are where the action is. Haemophilus influenzae hangs onto the #1 spot; Mycosplasma genitalium makes a reappearance at #9 after one issue in the wilderness; and Methanococcus jannaschii is lurking at #11. Senior author on all three papers is Craig Venter, president of The Institute for Genomic Research (TIGR), now located in Rockville, Maryland.

   Venter has assembled a crack team of sequencers at TIGR to take advantage of a technique he devised once controversial, now not only orthodox but extremely productive. Called whole-genome random sequencing, it skips what was thought to be a crucial first step in reading an organism's genome: mapping. Venter's approach is to sequence clones without knowing how those clones fit together, using smart software to build up the complete sequence (for details, see page 3 of this issue, and Science Watch, 8[1]:7, January/February 1997).

   As a tour de force these sequences are remarkable enough. But the reason each is so exciting is that the sequence offers insights into the way the organism works. H. influenzae, for example, needs large amounts of glutamate in its growth media. A search of the complete sequence failed to find evidence of three genes that code for enzymes essential to the tricarboxylic acid (TCA) cycle. But glutamate can be fed into the TCA cycle via enzymes that H. influenzae can produce, so despite its lack of a complete TCA cycle the organism can get by if given enough glutamate.

   In the same vein, the sequence of M. jannaschii has also answered some fundamental questions about the diversity of life. The organism comes from hot vents some 3 km beneath the Pacific, and its sequence vindicates the 20-year-old theories of Carl Woese, of the University of Illinois. Woese proposed adding a third major grouping, the Archaeons, to the Prokaryotes and Eukaryotes, and also said that archaeons and eukaryotes were more like each other than either was like prokaryotes. The sequence shows that fewer than half the genes of M. jannaschii are familiar, and those that are resemble eukaryote genes much more closely than they resemble prokaryote (bacterial) genes, a perfect result for Woese.

   M. genitalium is a pathogen famous for having the smallest genome of any free-living organism. Despite that, genes seem to be repeated even within its minimal genome. Although that seems contradictory, the gene in question is for the protein that elicits the host's immune response, which is repeated nine times and occupies almost 5% of the total genome. It seems likely that this repetition allows the bacterium to recombine its main antigen, thus evading the host's detection mechanisms.