The Deepest Branches

For this article, Steve Bunk interviewed Karl O. Stetter, director, Institute of Microbiology, University of Regensburg, Germany, and Jay M. Short, chief executive officer, Diversa Corp., San Diego. Data from the Web of Science (ISI, Philadelphia) show that Hot Papers are cited 50 to 100 times more often than the average paper of the same type and age. G. Deckert, P.V. Warren, T. Gaasterland, W.G. Young, A.L. Lenox, D.E. Graham, R. Overbeek, M.A. Snead, M. Keller, M. Aujay, R. Huber, R.A. Feldman, J.M. Short, G.J. Olsen, R.V. Swanson, "The complete genome of the hyperthermophilic bacterium Aquifex aeolicus," Nature, 392:353-8, March 26, 1998. (Cited in more than 255 papers since publication) Increasingly, the tree of life is assuming the semblance of a bush. But even a bush has its deepest branches, and in presenting the first complete genome of a hyperthermophilic bacterium, this paper took important steps toward characterizing the last common ancestor of all extant life. That organism also was probably the last common ancestor of the two prokaryote groups, Bacteria and Archaea.1 The latter includes microbes from such extreme environments as boiling deep sea vents, a possible birthplace of life on Earth. The first hyperthermophile to be completely sequenced was an archaea, Methanococcus jannaschii.2 The second one, Aquifex aeolicus, was described in this paper. "It was a bacterium, not an archaea, and a hyperthermophile, so it was exciting for many people to compare it to [Escherichia] coli and other bacteria," notes the man who first collected and cultured A. aeolicus, Karl O. Stetter, director of the Institute of Microbiology at the University of Regensburg, Germany. He adds, "It clearly comes out when you compare genomes that there are information-processing genes on one hand and housekeeping genes for energy and metabolism on the other hand." Especially in information processing, A. aeolicus genetically resembles E. coli much more closely than it does M. jannaschii. But concerning the "housekeeping" genes, there's much evidence of horizontal transfer between A. aeolicus and the other domain of life, Eucarya. A. aeolicus's 1,512 open reading frames (presumably equivalent to genes) encode the complex metabolic machinery of a chemolithoautotroph--an organism that uses inorganic sources for both biosynthesis and energy. Yet it also has a complex respiratory apparatus that allows use of the very low concentrations of oxygen that might have existed near the dawn of life. Stetter originally harvested the microbe in a mud sample from extremely hot water at a beach in the volcanic Aeolian Islands of southern Italy (hence the name, Latin for "Aeolian water-maker"). Back at the lab, he and colleague Robert Huber isolated and purified the bacterium, then cultivated it. Stetter has amassed 1,500 hyperthermophiles, the world's largest collection, now owned by the San Diego-based biotechnology company he cofounded, Diversa Corp. He decided A. aeolicus should be sequenced at Diversa, forgoing authorship on the paper in favo of Huber. The paper's senior author, Ronald V. Swanson, recently left Diversa to join San Diego biotech startup Syrrx Inc. Coauthor Jay M. Short, chief executive officer and head of research at Diversa, says, "The Aquifex paper really stems from our early days, when we were focused on our cultured collection. We have now moved to whole genome engineering. To understand the interactions of gene pathways and genomes is the frontier." He says Diversa's current environmental libraries contain essentially all the genes for more than one million strains of uncultured microorganisms, and more than one billion genes can be screened per day. "Rational" approaches such as modeling kinetic pathways are being combined with such proprietary, "nonrational" techniques as observing millions of mutagenic variants in accelerated DNA mutation models. The objective of these "directed evolution" techniques is to develop new small molecules for various applications in biomedicine and chemistry. Such intergenomic studies among hyperthermophiles permit potential recombination of genes across species. Proteins can be engineered that work at high or low temperatures, or with increased reaction rates, or with improved pH and salt tolerance. Short concludes, "Understanding these enzymes as factories and engines for manufacturing molecules is very important." Steve Bunk (sbunk@uswest.net) is a contributing editor for The Scientist. References 1. R.F. Doolittle, "Microbial genomes opened up," Nature, 392:339-42, March 26, 1998. 2. S. Bunk, ed., "Hot Papers: Genetics," The Scientist, 12[12]:11, June 8, 1998.

The Deepest Branches

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