Genetics

Edited by: Eugene Russo F. Kunst, N. Ogasawara, I. Moszer, A.M. Albertini, G. Alloni, V. Azevedo, M.G. Bertero, P. Bessières, A. Bolotin, S. Borchert, R. Borriss, L. Boursier, A. Brans, M. Braun, S.D. Brignell, S. Bron, S. Brouillet, C.V. Bruschi, B. Caldwell, V. Capuano, N.M. Carter, S.K. Choi, J.J. Codani, I.F. Connerton, N.J. Cummings, R.A. Daniel, F. Denizot, K.M. Devine, A. Düsterhöft, S.D. Ehrlich, P.T. Emmerson, K.D. Entian, J. Errington, C. Fabret, E. Ferrari, D. Foulger, C. Fritz, M. Fujita, Y. Fujita, S. Fuma, A. Galizzi, N. Galleron, S.Y. Ghim, P. Glaser, A. Goffeau, E.J. Golightly, G. Grandi, G. Guiseppi, B.J. Guy, K. Haga, J. Haiech, C.R. Harwood, A. Hénaut, H. Hilbert, S. Holsappel, S. Hosono, M.F. Hullo, M. Itaya, L. Jones, B. Joris, D. Karamata, Y. Kasahara, M. Klaerr-Blanchard, C. Klein, Y. Kobayashi, P. Koetter, G. Koningstein, S. Krogh, M. Kumano, K. Kurita, A. Lapidus, S. Lardinois, J. Lauber, V. Lazarevic, S.M. Lee, A. Levine, H. Liu, S. Masuda, C. Mauël, C. Médigue, N. Medina, R.P. Mellado, M. Mizuno, D. Moestl, S. Nakai, M. Noback, D. Noone, M. O'Reilly, K. Ogawa, A. Ogiwara, B. Oudega, S.H. Park, V. Parro, T.M. Pohl, D. Portetelle, S. Porwollik, A.M. Prescott, E. Presecan, P. Pujic, B. Purnelle, G. Rapoport, M. Rey, S. Reynolds, M. Rieger, C. Rivolta, E. Rocha, B. Roche, M. Rose, Y. Saie, T. Sato, E. Scanlan, S. Schleich, R. Schroeter, F. Scoffone, J. Sekiguchi, A. Sekowska, S.J. Seror, P. Serror, B.S. Shin, B. Soldo, A. Sorokin, E. Tacconi, T. Takagi, H. Takahashi, K. Takemaru, M. Takeuchi, A. Tamakoshi, T. Tanaka, P. Terpstra, A. Tognoni, V. Tosato, S. Uchiyama, M. Vandenbol, F. Vannier, A. Vassarotti, A. Viari, R. Wambutt, E. Wedler, H. Wedler, T. Weitzenegger, P. Winters, A. Wipat, H. Yamamoto, K. Yamane, K. Yasumoto, K. Yata, K. Yoshida, H.F. Yoshikawa, E. Zumstein, H. Yoshikawa, A. Danchin, "The complete genome sequence of the Gram-positive bacterium Bacillus subtilis," Nature, 390:249-56, 1997. (Cited in more than 350 papers since publication) Comments by Frank Kunst, head of laboratory of genomics of microbial pathogens, Institut Pasteur, Paris, France Courtesy of Institu Pasteur Institut Pasteur researchers Philippe Glaser, Frank Kunst, and Antoine Danchin (left to right) lead the B. subtilis sequencing efforts that culminated in this 151-author paper. Back in 1990, before the time of central, automated sequencing facilities, five European labs started a pilot program to investigate the feasibility of sequencing the genome of the well-characterized Gram-positive bacterium Bacillus subtilis. Of interest in part for its ability to secrete large amounts of industrially important enzymes, B. subtilis is also the paradigm of a sporulating bacteria strain that includes species such as Bacillus anthracis, the bacterium that causes anthrax and has reportedly been grown for use as a bioterrorist agent. Originally a collaboration among American and European labs, the B. subtilis project suffered a funding shortage in 1991 when the National Institutes of Health backed out of the project, preferring to focus on human genome sequencing. Soon after, though, a consortium of seven Japanese labs, coordinated by Naotake Ogasawara of the Nara Institute of Science and Technology, came on board. And by 1993, the B. subtilis project, funded by the European Commission, had grown to include 25 European labs from six European countries, the Japanese labs, two U.S. teams, and one Korean team. This paper was the first to report the bacterium's complete genome sequence. Like the sequencing of several bacteriophages, the sequencing of the 4,214,810 base pairs and 4,100 protein-coding genes of the B. subtilis genome helped elucidate the role of bacteriophages in the evolution of methods of gene transfer. Sequencers' discovery that the genome included prophages--genomes inserted into specific sites of bacterial chromosomes--demonstrated the importance of bacteriophage infection in the evolution of horizontal gene transfer, the process by which genes are transferred between species via a virus or bacterium rather than via gametes donated from parents to progeny (vertical gene transfer). A comprehensive compilation of B. subtilis sequence data is available on the SubtiList Web Server at bioweb.pasteur.fr/GenoList/SubtiList. Also resulting from the B. subtilis project: a follow-up effort to investigate the B. subtilis genes discovered with no known function. Researchers led by S. Dusko Ehrlich of the Laboratoire de Génétique Microbienne at the Institut National de la Recherche Agronomique in Jouy-en-Josas, France, are disrupting the genes one by one and examining the resulting phenotypic changes. They hope to find the essential, core genes of a bacterium. As was the case with the sequencing of Escherichia coli,1 scientists would have done things a little differently if they'd known then what they know now, says lead author Frank Kunst. Rather than using a clone-by-clone approach of slowly building up the genome from ordered pieces of DNA, they'd employ the quicker, more efficient whole-genome shotgun approach: Entire genomes of millions of base pairs are cut into small 500-base-pair pieces, then randomly sequenced and assembled using computer software. According to Kunst, investigators now see in hindsight what made the early 1990s effort a much more primitive approach than more recent sequencing efforts: less powerful bioinformatics tools, cloning difficulties using an E. coli host with many of the DNA fragments from B. subtilis, and the limited DNA sequencing capacity of each participating European lab. "We've learned from the Bacillus project and [now] use modern and powerful techniques to complete the genomes of other bacteria," says Kunst of his lab's current work. He cites specifically ongoing efforts by a consortium of 10 European laboratories to determine the genome sequence of Listeria monocytogenes, a Gram-positive bacterium that can cause serious foodborne infections in pregnant women, newborns, the elderly, and immunocompromised adults. The project, coordinated by Institut Pasteur researchers Pascale Cossart and Philippe Glaser, is slated for completion in about a year; the annotation of the genome will likely require six additional months. E. Russo, "Genetics: Comments by Fred R. Blattner," Hot Papers, The Scientist, 13[15]:17, July 19, 1999.

Genetics

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