Completion of Haloarcula marismortui Genome Sequencing Featured in Genome Research
Institute for Systems Biology Researchers Led International Effort

SEATTLE -- Tuesday, November 2, 2004 -- Scientists at the Institute for Systems Biology (ISB) in collaboration with researchers from National Yan Ming University (NYMU) in Taiwan and University of Texas at Austin have fully sequenced the complete genome of Haloarcula marismortui, a microorganism that thrives in the Dead Sea.

Their findings are featured on the cover of this month's issue of the journal Genome Research. This highly collaborative study was supported by research grants from multiple funding agencies including the National Science Foundation, U.S. Department of Energy and Department of Defense and the National Science Council of Taiwan and spearheaded by Drs. Nitin S. Baliga, ISB senior scientist and his colleague Victor Wailap Ng (currently at NYMU)also of ISB.

Unlike E. coli, which is a bacterium, H. marismortui belongs to a distinct class of microorganisms called the Archaea. Recent studies suggest that the evolution of the first eukaryotic organism might have resulted from the fusion of genomes from a bacterium and an archaeon. Many archaeal organisms dominate extreme environments such as those with temperatures above boiling, at the bottom of the ocean, etc. that were previously thought to be uninhabitable by any kind of life form. A complete understanding of this and other archaeal organisms may lead to applications of a true biological systems approach to problems related to energy, bioremediation and health.

Four years ago, more than 40 scientists across North America and Europe participated in a monumental effort to determine the complete genome sequence of Halobacterium NRC-1, an archaeal organism, which, like H. marismortui, proliferates in saturating salt solutions (~10 times the salinity of sea water).

In contrast, sequencing of the ~4.3 million base pair genome of H. marismortui, which is twice as big as Halobacterium NRC-1 genome, required only 15 scientists. Modern sequencing technologies, combined with state-of-art open source computational software developed at the ISB have automated many of the processes required for decoding the genome information.

This genome decoding process used novel strategies including prediction of three-dimensional protein structures using methods pioneered by Drs. Richard Bonneau (now at ISB) and David Baker at the University of Washington. Prediction of these three-dimensional protein structures provides a highly sensitive detector that enables the identification of their specific functions. In conjunction with linear string similarities this novel genome decoding effort has provided functional information for a far greater number of proteins in H. marismortui than has been previously achieved in other microbial genome sequence annotations.

Traditionally, biologists have studied organisms one gene or one protein at a time. In a systems approach, all of the genes and proteins and interactions between them are simultaneously analyzed. ISB researchers are focused on using model systems such as Halobacterium to learn how to practice systems biology and on applying these systems approaches to learn how the immune system functions.

"Using systems approaches, simple model organisms such as Halobacterium NRC-1 and H. marismortui are expected to provide insights into deciphering their networks of life and in doing so will aid in deciphering the far more complex networks of life -- for example, the human immune response," stated Dr. Baliga. "Further, the ability to study two related genomes will provide infinitely more insights than studying one at a time."

Both Halobacterium NRC-1 and H. marismortui dominate highly saline environments that experience frequent fluctuations in a variety of environmental factors including those that cause severe DNA damage. These microorganisms have learned, through millions of years of evolution, efficient ways to negotiate these constant stress conditions by employing clever strategies. For example, both of these archaea have a high degree of negatively charged amino acids on the surface of their folded proteins. This unusual property enables these proteins to withstand high salinity in the cytoplasm (required to counterbalance external salinity) which otherwise causes most proteins to collapse and lose function.

Dr. Baliga and co-workers have conducted extensive genomic studies on the unusual properties of Halobacterium NRC-1 to provide considerable insight into the biology of these organisms. For example, two years ago they reported a study in the Proceedings of the National Academy of Sciences that described the ability of these cells to sense quality and quantity of light and oxygen in the environment to carefully control three possible processes for energy transduction.

Interestingly, relative to Halobacterium NRC-1, H. marismortui has nearly five times as many sensors for light and oxygen and therefore is believed to have the capacity to adapt its physiology to more diverse environments. However, the study revealed that both of these organisms shared a common ancestor millions of years ago and through the course of evolution Halobacterium NRC-1 appears to have shed nearly half of its genes, perhaps to streamline its life cycle.

This raises interesting questions regarding genome evolution in closely related species. Because of its close relatedness to Halobacterium NRC-1, H. marismortui now provides a simple system in which to understand these important questions. It will also help scientists understand the molecular and genetic mechanisms of behavioral differences among closely related species. In fact, scientists at ISB believe that the study of these simple microorganisms as model systems will lead to developments of tools, technologies and new approaches to scientific inquiry that will in turn further the field of systems biology and ultimately lead to predictive, preventive and personalized medicine.

About the Institute for Systems Biology
The Institute for Systems Biology (ISB) is an internationally renowned non-profit research institute dedicated to the study and application of systems biology. ISB's goal is to unravel the mysteries of human biology and identify strategies for predicting and preventing diseases such as cancer, diabetes and AIDS. The driving force behind the innovative "systems" approach is the integration of biology, computation, and technology. This approach allows scientists to analyze all of the elements in a system rather than one gene or protein at a time. Located in Seattle, Washington, the Institute has grown to seven faculty and more than 170 staff members; an annual budget of more than $25 million; and an extensive network of academic and industrial partners. For more information, visit: www.systemsbiology.org