Microbiologists Make Discoveries in the Sea, in the Neighborhood

The Faculty of 1000 is aWeb-based literature awareness tool published by BioMed Central. For more information visit www.facultyof1000.com. Microbiology has come a long way since the days of Anton van Leeuwenhoek and his "very little living animalcules, very prettily a-moving." The animalcules were, of course, bacteria, and Leeuwenhoek's 17th century observations were among the first written records of microbial life. Now, as exemplified by two recent Faculty of 1000 papers, microbiologists are answering questions that Leeuwenhoek and his peers probably could not imagine. In one paper, marine microbiologists explain how they cultivated previously unculturable bacteria.1 In the other, researchers describe a new computational method for comparing genomic sequences from distantly related microbial species.2 In 1990, Oregon State University's Stephen Giovannoni discovered a new bacterium in the Sargasso Sea--a two-million-square-mile ellipse of clear, warm water in the North Atlantic. He and his collaborators named the organism SAR11. They started finding members of the SAR11 clade practically everywhere, from coastal waters to depths of 3,000 meters, yet nobody could cultivate the elusive organisms in the lab. "Ninety-nine percent or more of microbial species we can't currently cultivate," says Faculty of 1000 member Ian Paulsen, the Institute for Genomic Research, Rockville, Md., "and SAR11 has always been a poster child of these uncultivable organisms." Scientists are unsure why so many microbes are unculturable. "The way we grow bacteria in the lab is really quite artificial," says Paulsen, and those that don't grow are likely missing some unknown, essential natural factor. Now, the uncultivables may be culturable after all. This year, Giovannoni and coauthors finally isolated SAR11, making the bacterium one of the smallest free-living cells in culture. "It has been quite a significant break through," says Paulsen. "People have spent years trying to grow SAR11." As Giovannoni explains, the team's effort "was very deliberate. We had hypotheses and we developed a strategy that addressed those hypotheses. We took a very structured approach to culturing uncultured organisms. The tricks that made it work were that we were able to screen a large number of cultures and detect a very low number of cells in them and that we used pristine sea water as a medium." In recent years, many microbiologists have come to believe that they didn't need to work with the whole organism as long as they had sufficient genetic material, Giovannoni says. But "we are coming around full circle." The next step in the SAR11 research, says Giovannoni, is to sequence the newly cultivated organisms. In the second paper, Igor Rogozin, Eugene Koonin, and their coauthors from the National Institutes of Health and the University of South Carolina developed a new computational method for comparing genomes and delineating clusters of genes known as gene neighborhoods. These neighborhoods, Koonin explains, are not necessarily found in their entirety in any single genome. Rather, they are statistically significant groups of genes that are partially shared among many different genomes, are evolutionarily conserved, and have a common functional theme. "Imagine a swamp with a number of islands," he explains, where some are connected by boardwalks but others are completely isolated. If someone wants to walk among the islands but doesn't know where the boardwalks are, he would need a map to locate a set of interconnected islands. Researchers essentially used a graph-theoretical approach to determine their steps, according to Koonin. The islands represent genes, and a set of interconnected islands represents a gene neighborhood. They pulled out a map filled with every gene from 31 distantly related genomes, and they identified 188 different gene neighborhoods. "As you start sequencing distantly related bacteria, there is less and less conservation of gene order," explains Faculty of 1000 reviewer Arcady Mushegian, Stowers Institute for Medical Research, Kansas City, Mo. "So it becomes very difficult to compare these sequences and detect evolutionarily conserved clusters." Koonin's team has described a "robust way to study the conservation of gene order when this gene order is not strictly conserved but is conserved somewhat, which is usually the case. In biology, nothing is strictly conserved," he says. Koonin and colleagues observed a phenomenon known as 'genomic hitchhiking.' Some neighborhoods had a small number of genes that did not seem to be functionally connected to their neighbors. These so-called hitchhikers are probably in the location because they are expressed at the same level as the other neighborhood genes, suspects Koonin. Or, equally likely, the hitchhikers may have hidden functions. Genome comparisons, says Koonin, are important tools for studying genome evolution. "Life is basically recorded in genomes, so understanding how genomes evolved is fundamentally important to answering the question, 'How did life evolve?'" And that is a question that van Leeuwenhoek probably dared not even consider. Leslie Pray (lpray@nasw.org) is a freelance writer in Leverett, Mass. References 1. M.S. Rappe et al., "Cultivation of the ubiquitous SAR11 marine bacterioplankton clade," Nature, 418:630-3, Aug. 8, 2002. 2. I. B. Rogozin et al., "Connected gene neighborhoods in prokaryotic genomes," Nucleic Acids Research, 30:2212-23, May 15, 2002.

Microbiologists Make Discoveries in the Sea, in the Neighborhood

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