International Consortium Decodes Mouse Genome; Institute for Systems Biology Plays Key Role in Research That Could Shed Light on Human Diseases.

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SEATTLE--(BUSINESS WIRE)--Dec. 5, 2002

The Institute for Systems Biology (ISB), a non-profit research institute dedicated to the study and application of systems biology announced today that researchers at the Institute, as part of an international collaboration, have completed the initial analysis of the mouse genome.

This achievement will help scientists gain a better understanding of disease in humans.

"Comparative genomics is probably the most powerful method for establishing what is functional in the genome and what isn't," said Arian Smit, a senior scientist at the Institute. "Getting this kind of insight into the mouse genome can give us a better understanding of human disease. The mouse and human genome have remarkable similarities." Dr. Smit and colleagues at the Institute also had participated in the initial genome analyses of the two previously sequenced vertebrate genomes, human and pufferfish.

Systems biology uses an innovative approach that allows scientists to analyze all of the elements in a system rather than one gene or protein at a time. The very first step in Systems Biology is the construction of a "parts list", which can provide scientists with a road map of biological systems. The analysis of completed vertebrate genomes is the basis for the identification of all functional parts, primarily the genes, in the genome. As a long-studied experimental model for human diseases, the mouse genome has always been first in line among mammals to be decoded.

Although the human and mouse genome are relatively close cousins among mammals, the mouse genome has evolved at a faster rate than most other mammalian genomes. Mice and humans became separate species around the time of the extinction of the dinosaurs, 65 million years ago. Since that time on average one of every two letters in the genetic code of both species have changed, compared to one of three for human, cow or dog. This higher divergence is beneficial for scientists, as it allows conserved, potentially functionally important features to stand out more in a comparative analysis of the human and mouse genomes. On the other hand, it did make the alignment of the sequences a bit more of a challenge.

Still, almost half of the human genomic sequence can be found in mice. In contrast, sequence comparison between the much more distantly related pufferfish and mammals is primarily limited to regions coding for proteins, which only comprise about three percent of our genome. Most of the remainder of a mammalian genome is comprised of copies of selfish DNA sequences, like retroviruses, in various forms of decay. These nonfunctional sequences, called repetitive or 'junk DNA', are the scientific specialty of Dr. Smit, who has lead the sections in all three vertebrate genome papers on this aspect of the genome.

For most scientists the interest in junk DNA is limited to recognizing it so that they can focus on the remaining, potentially functional regions, but several key findings came out of analyzing the repetitive DNA in mouse. First, the mouse genome is about 15 percent smaller than the human genome, but more junk has actually been introduced in the mouse than in the human genome. Instead, the smaller size is due to more rigorous cleaning of the junk in the mouse through large scale deletions. Over 40 percent of the genome of the common ancestor of human and mouse has been deleted in mouse. Second, the rate at which changes accumulate in mouse has been twice higher than in human. And third, mysteriously, the same type of selfish sequences appear to have independently accumulated at the same places in the two genomes, revealing something of a higher organization in our genome.

The international research team included groups from the Washington University in St. Louis, the Whitehead Institute at MIT, the University of California at Santa Cruz, Penn State University, the Sanger Institute, European Bioinformatics Institute in England, and multiple other institutions. The research will be published in this week's issue of Nature (www.nature.com).

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, arthritis and AIDS. The driving force behind the innovative "systems" approach is the integration of biology, computation, technology and medicine. 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, Wash., the Institute has grown to more than 170 faculty and staff members, and has an extensive network of academic and industrial partners. For more information, contact: www.systemsbiology.org.