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Horizontal gene transfer is now better understood
Conservation of genetic resources may pay off in improvements to human health, advances in bioremediation

| 21 March 2007

Two new studies by Berkeley scientists highlight the amazing promiscuity of genes, which appear to shuttle frequently between organisms, especially more primitive organisms, and often in packs.

Such gene flow, dubbed horizontal gene transfer, has been seen frequently in bacteria, allowing pathogenic bacteria, for example, to share genes conferring resistance to a drug. Recently, two different species of plants were shown to share genes as well. The questions have been: How common is it, and how does it occur?

In a recent report in the Proceedings of the National Academy of Sciences (PNAS), Berkeley and Lawrence Berkeley National Laboratory (LBNL) researchers analyzed more than 8,000 different families of genes coding for proteins - families that represent the millions of proteins in all living creatures - to assess the prevalence of horizontal gene transfer.

They found that more than half of all the most primitive organisms, Archaea, have one or more protein genes acquired by horizontal gene transfer, as compared to 30 to 50 percent of bacteria that have acquired genes this way. Fewer than 10 percent of eukaryotes - plants and animals - have genes acquired via horizontal gene transfer.

In a second report, published online by Nature on March 7, two species of bacteria living together in the pink slime of an acidic California mine were found to share large groups of genes. These genes code for proteins that work together, so by acquiring the entire block from another organism, bacteria can gain a new function that helps them adapt more quickly to the same type of environment - in this case, a hot, highly acidic, metal-rich broth.

This is the first observation of exchange of very large genomic blocks between organisms in a natural microbial community, says Jill Banfield, a Berkeley professor of earth and planetary science and of environmental science, policy, and management who is also an LBNL researcher. Banfield led the team of researchers from LBNL, Oak Ridge National Laboratory (ORNL), Lawrence Livermore National Laboratory, and the U.S. Department of Energy's Joint Genome Institute.

"One of the key questions being debated was, 'Is horizontal gene transfer extensive and rampant, or is it a relatively rare event?'" says Sung-Hou Kim, a Berkeley professor of chemistry and co-author of the PNAS paper. "This becomes important in classifying organisms and comparing whole genomes to find their relationships.

"Our study shows that gene transfer is fairly common, but the extent in a given organism is fairly low - that is, most organisms have received one or more genes from a closely related organism. And while it's very likely that genes are transferred in chunks that are linked metabolically, I bet it's not always true. If a group of genes doesn't have value in a new environment for a new organism, it's not going to stick around."

"This provides important information about the conservation of genetic resources to enable life to survive and thrive," says ORNL's Bob Hettich, a co-author of the Nature paper. "Ultimately, the basic knowledge gained from this research will lead to a greater understanding of genetic diversity in related organisms and should lead to developments in human health and bioremediation."

Which organism, which proteins?

Though the Nature findings about mine slime bear on the issue of horizontal gene transfer, the study's main goal was to detect, with high resolution, which organism is able to carry out what function within a natural, uncultivated microbial community, according to Banfield.

"In addition to revealing a history of genetic exchange between two dominant organism types in the mine," says Banfield, "we show that it is possible to identify a large fraction of the proteins from coexisting organisms and determine which organism most of the proteins come from, even if the organisms are quite closely related."

Banfield leads a long-term study of the community of organisms in mine slime obtained from the Richmond Mine near Redding. This microbial biofilm has turned out to be an ideal research subject, Banfield says, because the simple community contains few enough organisms that they can be used as a model system to uncover aspects of how microbes interact with each other and their surroundings in ways that are difficult or impossible in other environments.

In 2002, the mine was the source of samples for the first fairly comprehensive community genomic, or metagenomic, characterization of a natural microbial consortium. In 2005, Banfield and colleagues presented the first relatively large-scale analysis of the proteins that consortia members make to carry out the various metabolic tasks needed for life underground - work that revealed information about the machinery used to adapt to the extreme conditions in which they live. More recently, in 2006, research scientist Brett Baker, Banfield, and colleagues reported that the biofilms harbor novel archaeal organisms that appear to be extremely small compared to other life forms.

"Analysis of how microorganisms respond to their environments and the role of exchange of genetic material in adaptation and evolution is important if we are to understand important environmental processes such as acid mine drainage, or even degradation of cellulose for ethanol production by microbial communities," adds Banfield.

In their new paper, the researchers combine metagenomics with strain-resolved shotgun proteomics to show that different organisms are exchanging large blocks of their genes.

"Who's there and what are they doing are key questions in microbial ecology," says Banfield's colleague Vincent Denef, a postdoctoral researcher in the Department of Earth and Planetary Science. "Our high-resolution, mass spectrometry-based community proteomics approach answers both at the same time. We can now tell apart closely related organisms, which we previously would have grouped as one species, and we can monitor and discriminate their behavior within the same natural community. These abilities will allow us to understand the implications of small differences in genome sequence and content on ecological performance, one of the key goals of the current microbial genomic sequencing efforts."

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