The U.S. Department of Energy will spend more than $12 millionover the next three years to unravel the genetic mysteries of ancientforms of bacteria that survive in some of the earth's most hostileenvironments.The program involves sequencing the genomes of archaea bacteriato determine genetic functions that allow them to thrive in habitatssuch as toxic waste dumps, extreme ocean depths, boilingtemperatures and saturated salt solutions.Carl Woese, of the University of Illinois, Urbana, who discoveredthe existence of the archaea in 1976, said the project will provideinsight into the human evolution as well as develop industrialapplications from enzymes the archaea produce to survive."If you look at the planet as an alien," Woese told BioWorld, "thefirst impression you get is of microbial life. Microorganisms makeup the most biomass, sit at the base of the food chain as the ultimaterecyclers and either directly or indirectly are responsible for theatmosphere. We can therefore learn all manner of things fromthem."Added Woese, "Photosynthesis is a bacterial invention and our kindof respiration is a bacterial invention. The higher forms of life couldnot have evolved without bacteria."Prior to Woese's discovery of archaea, life was divided intoprocaryots, single-cell organisms without a nucleus, and eucaryots,organisms (such as humans) with multiple cells and nuclei. Bacteriawere among the procaryots, but when Woese analyzed microbesthat lived in extreme environments, such as those with boiling wateror no oxygen, he found they were different. The archaea bacteriaconstituted a third form of life, and according to Woese, they aremore closely related to humans than other bacteria."If we want to study the structure of the eucaryot cells, we can learna lot from the archaea," he said.J. Craig Venter, director of The Institute for Genomic Research(TIGR), said the DOE-funded project, called the Microbial GenomeInitiative, will yield the first complete organism gene sequences andfor the first time give researchers complete genomes to compare.Venter's institute, in Gaithersburg, Md., will collaborate withWoese on one phase of the project. In the first year they willanalyze Methanococcus jannaschii, which exists at the base of aPacific Ocean thermal vent and produces methane.Another project will be conducted by Robert Weiss of theUniversity of Utah in Salt Lake City. During the first year Weisswill sequence the genome of Pyrococcus furiosus, a marine archaeathat lives at extreme high temperatures, about 100 degrees celsius.A third program will involve Genome Therapeutics Corp., ofWaltham, Mass., and John Reeve of Ohio State University,Columbus. Their first target will be to sequence the genes ofMethanobacterium thermoautotrophicum, a methane producerpresent in sewage sludge.In the first year, DOE will spend about $3 million and plans toallocate more than $9 million over the succeeding two years. TIGRis scheduled to get a total of $6.7 million; Genome Therapeutics,$4.6 million; the University of Utah, $1.8 million; and theUniversity of Illinois, $560,000."We will be able to sequence five complete genomes," Venter said."Over the next three years we will develop a wealth of informationthat never existed before."Dave Smith, DOE's director of Health Effects and Life ScienceResources, said the project is an outgrowth of DOE's HumanGenome Program."With the development of the genome project at DOE and NationalInstitutes of Health (NIH), sequencing has become faster andcheaper and the technology has opened up new targets," he toldBioWorld.The archaea, he said, are prime subjects to study in terms of theirnear-term applications, such as toxic waste and oil spill clean-up,and alternative energy production."The objective," Smith said, "is that if you can understand what it isthat allows these archaea bacteria to live in such extremeconditions, you open the door to develop enzymes that work in suchareas as the high temperatures involved in an industrial process andin toxic waste clean-up."Venter said archaea sequences can be done quickly, in about sixweeks. By comparison, he added, sequencing for Escherichia colibacteria is in its fifth year of funding and still only 50 percentcomplete."The real challenge," Venter said, "will be to compare one entiregenome to the entire genome of another."Gerald Vovis, senior vice president of research and development atGenome Therapeutics, said sequencing the archaea is easier thanother genomes, in part, because they aren't as large (only millionsof base pairs compared with billions in humans) and the genes arenot interrupted by introns, which are considered non-functioningportions of DNA .Using the multiplex gene sequencing technology licensed fromHarvard University,Genome Therapeutics said it plans to sequence 1.7 megabases in thefirst year, 4.2 megabases in the second year and nearly 7 megabasesin the third year.In addition to the Methanobacterium thermoautotrophicum,Genome Therapeutics said that during the three-year project it willanalyze Rhodococcus rhodochrous, which biodegrades toxic waste,Methanopyrus kandleri, a methanogen that exists in boiling water,Synechococcus, a unicellular marine cyanobacterium, andHaloferax volcanii, which grows in salt saturated solutions.Fenel Eloi, Genome Therapeutics' chief financial officer, said allthe participants in the Microbial Genome Initiative bid for theproject.Eloi suggested the selection of Genome Therapeutics and theUniversity of Utah, both of which use multiplex gene sequencing,and TIGR, which uses ABI sequencers (made by AppliedBiosystems, a division of Perkin-Elmer Corp, in Norwalk, Conn.),is a validation of those two sequencing methods."There are various sequencing methodologies," Eloi said. "DOEconsidered a lot of bids and by awarding the projects to GenomeTherapeutics, the University of Utah and TIGR, (DOE) was makinga statement."As the only commercial company involved in the project, GenomeTherapeutics will be able to patent genes it discovers forcommercial use.DOE said all the information in the Microbial Genome Initiativewill be deposited in public databases, such as GenBank, which isrun by the NIH's National Center for Biotechnology Information.

-- Charles Craig

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