Progress, and Applications
of the Human Genome Project
Sponsored by the U.S. Department of Energy Human Genome Program
Human Genome News Archive Edition
Human Genome News, July-September 1996; 8:(1)
Researchers Present Archaea Genome Sequence
In a major scientific breakthrough, a team of DOE-funded researchers reported in the August 23 issue of Science (273, 1058-73) that they had sequenced the first complete genome of a microorganism that confirms the existence of the third major branch of life on earth [see HGN 7(6), 12-13]. For the first time, researchers can trek boldly across uncharted terrain to make large-scale comparisons among the three domains of life at the genomic level. Researchers from The Institute for Genomic Research (TIGR); University of Illinois, Urbana (UIU); and Johns Hopkins University presented the sequence for Methanococcus jannaschii, a member of the Archaea domain of life. The other two major life groups are prokaryotes (bacteria) and the more complex eukaryotes, which include plants, animals, and humans.
"This brings to closure the question of whether Archaea are separate and distinct life forms," said Craig Venter (TIGR). "In decoding the genetic structure of Archaea, we were astounded to find that two-thirds of the genes do not look like anything we've ever seen in biology before." According to the Science paper, only about 38% of M. jannaschii genes match a gene with a known cellular function already entered in sequence databases. Comparisons also were made with genes found in the genomes of the other two complete microbial genomes sequenced by TIGR, those of Mycoplasma genitalium and Haemophilus influenzae.
More extensive gene comparisons will help scientists better understand the evolution of all three branches of life. Early analysis points to a closer shared evolutionary heritage for the Archaea and eukaryotes. This is particularly evident in the genes controlling information processing: transcription, translation, and DNA replication. Features shared with bacteria include the lack of a nucleus and strongly similar metabolic genes. "We can look at the Archaea as the living fossils of our prokaryotic [bacterial] ancestors," observed Carl Woese (UIU).
Random Sequencing Strategy
Sequencing of the 1.7-Mb M. jannaschii genome, which consists of three distinct genetic elements, was completed by a team led by Carol Bult (TIGR) in just over a year. Researchers applied a whole-genome random approach, using both a small-insert (2.5-kb average) plasmid library and a larger-insert (16-kb average) lambda library. All clones were sequenced from both ends, with the lambda library used to verify contigs built from assembled plasmid sequences. Data, including double the number of genes and proteins previously known for Archaea, are available on the Web.
Fulfilling a DOE Mandate
DOE and its predecessor agencies have a long history of support for genetic research growing out of their legislative mandate to understand the health effects of nuclear energy and radiation and the byproducts of other forms of energy production. DOE funded the Archaea research as part of its Microbial Genome Program (MGP), a complementary project to the Human Genome Program. MGP is headed by Jay Grimes of the DOE Office of Health and Environmental Research (firstname.lastname@example.org).
Begun in 1994, MGP's goal is to sequence microorganisms of interest to DOE's energy and environmental cleanup programs. M. jannaschii is the second genome completed in MGP. The first, M. genitalium, is a bacterium thought to be the simplest known self-replicating and free-living life form.
With a genome of just 580 kb, it provides researchers with a model for the minimum number of genes and protein products necessary for independent existence.
MGP Research Providing Clues to Understanding Genetics
Private companies, universities, and DOE laboratories are now sequencing an additional ten microbial genomes for MGP, including that of the most radiation-resistant life form ever found. This organism, Deinococcus radiodurans, was first discovered in spoiled beef thought to have been sterilized by radiation. The microbe is potentially useful for cleanup of radioactive wastes as well as for adding to the understanding of sensitive enzymes - responsible for monitoring and repairing damage to DNA caused by radiation and other environmental agents.
Completely Sequenced Genomes (Does not include viruses.)
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