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Lateral Thinking

For this article, Steve Bunk interviewed Claire M. Fraser, president, the Institute for Genomic Research, Rockville, Md. 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. K.E. Nelson, R.A. Clayton, S.R. Gill, M.L. Gwinn, R.J. Dodson, D.H. Haft, E.K. Hickey, J.D. Peterson, W.C. Nelson, K.A. Ketchum, L. McDonald, T.R. Utterback, J.A. Malek, K.D. Linher, M.M. Garrett, A.M. Stewart, M.D. Cotton

By | July 9, 2001

For this article, Steve Bunk interviewed Claire M. Fraser, president, the Institute for Genomic Research, Rockville, Md. 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.
K.E. Nelson, R.A. Clayton, S.R. Gill, M.L. Gwinn, R.J. Dodson, D.H. Haft, E.K. Hickey, J.D. Peterson, W.C. Nelson, K.A. Ketchum, L. McDonald, T.R. Utterback, J.A. Malek, K.D. Linher, M.M. Garrett, A.M. Stewart, M.D. Cotton, M.S. Pratt, C.A. Phillips, D. Richardson, J. Heidelberg, G.G. Sutton, R.D. Fleischmann, J.A. Eisen, O. White, S.L. Salzberg, H.O. Smith, J.C. Venter, C.M. Fraser, "Evidence for lateral gene transfer between Archaea and Bacteria from genome sequence of Thermotoga maritima," Nature, 399:323-9, May 27,1999. (Cited in 196 papers)



File Photo

Claire M. Fraser

This 1999 paper from the Institute for Genomic Research (TIGR) in Rockville, Md., greatly strengthens the case for the lateral transfer of genes from one species to another as a widespread phenomenon in the microbial world. But last month, to much media fanfare, TIGR reported that bacteria-to-human gene transfer is far less likely than what the publicly funded Human Genome Project postulated earlier this year.1 The debate is important because gene transfer from a prokaryote to a multicelled eukaryote would occur through the germ line, thus transforming itself into an inherited effect.

TIGR president Claire M. Fraser, senior author of this paper, says that eventually a set of rules might be devised concerning lateral gene transfer, perhaps involving engulfment of one cell by another. For now, though, the picture is becoming more complicated as evidence accumulates. "It's much easier to imagine all this going on when you're talking about single-cell organisms," she comments.

The paper announced the sequencing of the bacterium Thermotoga maritima, a hyperthermophile that was originally isolated from geothermally heated marine sediment. Comparing its genome to all 16 other then-sequenced microorganisms, the researchers found that almost one-quarter of its genes were most similar to those of archaeal species. Moreover, 81 of the 451 Archaea-like genes were clustered in regions that often contained a gene order conserved between Archaea and T. maritima, suggesting that large regions of DNA were acquired through lateral transfer. But the most compelling evidence came from phylogenetic analysis of the genes in question, which all grouped unambiguously with genes from archaeal rather than bacterial species.

The team also generated phylogenetic trees from 33 genes that were found to be homologous in all the then-sequenced genomes. Similarities were seen between these trees and others made conventionally, using ribosomal RNA (rRNA), but there were also significant differences. For instance, according to rRNA-based trees, the bacterial groups Aquificales and Thermatogales (the latter including T. maritima), are the most deeply branching known members of the bacterial domain. But that was not corroborated by the whole-genome comparison method.

What does this say about the origins of life? "To me, it raises as many questions as answers," Fraser acknowledges. However, she thinks it difficult to conceive of a single ancestor common to all organisms. Since this paper appeared, her group and a German team have found more evidence of lateral transfer between microorganisms, suggesting that the distinction between the bacterial and archaeal lineages is not absolute.2,3 Fraser and colleagues are now preparing a paper on lateral gene transfer between a photosynthetic bacterium and Archaea.

The main significance of this paper is to question the sufficiency of rRNA sequence-based classification of species, now that whole-genome comparisons are possible. Phylogenetic trees derived from a single molecule are an excellent start, especially in a new environment, Fraser notes, but they tell nothing about either the overall biology of a species or the extent of lateral gene transfer.

Steve Bunk (sbunk@uswest.com) is a contributing editor for The Scientist.
References
1. S.L. Salzberg et al., "Microbial genes in the human genome: Lateral transfer or gene loss?" Science, 292:1903-6, May 18, 2001.

2. J.F. Heidelberg et al., "DNA sequence of both chromosomes of the cholera pathogen Vibrio cholerae," Nature, 406:477-83, Aug. 3, 2000.

3. A. Ruepp et al., "The genome sequence of the thermoacidophilic scavenger Thermoplasma acidophilum," Nature, 407:508-13, Sept. 28, 2000.
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