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OF MICE AND MEN
Striking similarities at the DNA level could aid research
- Sabin Russell, Chronicle Medical Writer
Thursday, December 5, 2002

Matching newly minted genetic blueprints of mice and men, scientists have found a wealth of common chemistry between human beings and our tiny, four-legged ancestors.

In a series of publications today in the British scientific journal Nature, international teams of researchers published a nearly complete sequence of the genetic instructions of "Black 6," the most common breed of laboratory mouse, and matched its traits with the recently decoded human genome.

The genetic code of the mouse, published on a public Web site (www.ensembl.org), is expected to speed the work of laboratory scientists studying human diseases around the globe.

Dr. Francis Collins, director of the National Human Genome Research Institute, called the feat "a tremendously exciting and defining moment for biomedical research."

Among the findings are that mice and human beings both carry about 30,000 genes. Differences within these individual genes -- the precise sequences of the four-letter DNA code -- spell out the obvious differences between the two mammalian species. On a letter-by-letter basis, the genes are 85 percent the same.

Comparing the two genomes provides an evolutionary history of the two species, traced out in the diverging sequences of DNA. Mice, compared with humans, are more richly endowed in genes for sex, sense of smell, and immunity against pathogens.

TAIL LOST IN TIME
Human beings, in turn, carry the genes for growing a tail but apparently lack the ancient instructions -- lost in 75 million years of evolution -- for completing the process.

"Comparing genomic information across species allows us to glean important information about ourselves," said Eric Lander, director of the Whitehead/MIT Center for Genome Research and lead author of the 42-page report on the mouse genome.

By comparing the two genomes, researchers were able to discover 1,200 new human genes as well as 9,000 mouse genes never before identified.

Researchers found that 90 percent of genes linked to diseases were the same in mice as in human beings. The mouse has been the mainstay of laboratory research on human illness and will most likely become a more essential player in future studies.

About 25 million mice are used in laboratories around the world to test new drugs and new notions about the biochemical machinery of living organisms.

David Haussler, director of biomolecular science and engineering at UC Santa Cruz, worked on the species-to-species genome comparisons and is a co- author of the report. "This is very, very significant," he said. "You can learn so much more by comparing genes that evolved from a common ancestor than by studying one gene alone."

SURVIVING GENETIC MATERIAL
Raymond White, a human genetics researcher at UCSF's Ernest Gallo Clinic and Research Center in Emeryville, said the points of similarity between mouse and human genomes were vitally important -- they represent bits of genetic material that have survived, intact, over 75 million years of evolution. It's nature's way of saying something is working.

The research that has pinpointed these biologically "conserved" regions on the two genomes allows researchers to focus on the important parts of the human genome, and to ignore the much larger amounts of genetic information that is essentially meaningless -- some biologists call it "junk" DNA.

Mouse-to-human genome comparisons have shown that, in addition to common genes, the two species share a surprising amount of DNA code that controls when and how these genes turn on or off. These "regulatory regions," which might have been dismissed as "junk," take up more space on the genome than the genes themselves and promise to become a fertile area for research.

The catalog of mouse and human genes yielded by these genome projects will cut years of time from otherwise painstaking laboratory research. When a particularly interesting spot on a chromosome captures a researcher's attention, said White, it can take "three or four years, and three or four post-docs (PhD researchers), to find the specific gene." Now, with the gene catalog in hand, it can take five minutes of computer time.

The publication capped a two-year effort of the Mouse Sequencing Consortium,

a group of hundreds of scientists from 27 institutions in six nations. Funders of the $130 million effort include the National Institutes of Health and the Department of Energy in the United States, and the Wellcome Trust and the Medical Research Council in England.