Of Mice And Men

Scientists in six countries have published nearly the entire genetic makeup of the mouse — an accomplishment that demonstrates the lab animal's startling biological similarity to people and could yield new insights into human diseases.

The draft code of the mouse, 2.5 billion DNA letters long, is about 95 percent completed. Its release comes nearly two years after the human genetic makeup, or genome, was deciphered.

Scientists are already making side-by-side comparisons of the two genomes in hopes of better understanding human evolution and how genes function.

"We still need help interpreting this book of life," said Kerstin Lindblad-Toh of the Whitehead Institute/MIT Center for Genome Research. Lindblad-Toh is the senior program manager of the Mouse Genome Sequencing Consortium.

Among other things, scientists are already looking how human reproduction concentrated on long pregnancies and fewer offspring, and how the immune system constantly changes in a biological "arms race" against invading viruses and bacteria.

Details of the analysis appear in Thursday's issue of the journal Nature.

Celera Genomics, a Rockville, Md., biotechnology company, completed its own draft of the mouse genome more than a year ago but has made it available only to paying subscribers. In contrast, the international mouse genome project is being freely published on the Internet.

Scientists initially chose the mouse for sequencing because of its fundamental role in medical research over the past century. An estimated 25 million mice are used in research each year on such ills as cancer, diabetes, high blood pressure and obesity.

Initial comparison of the mouse and human genomes shows the species are closely related at a genetic level, even though the two last shared a common mammal ancestor 75 million years ago, when dinosaurs still roamed the Earth.

A full 99 percent of a mouse's genes have counterparts in humans, including genes that cause mice to have tails. In fact, researchers said they have identified only 300 genes that are unique to either creature.

The mouse genome is about 14 percent smaller in volume than its human counterpart, but each species has about 30,000 genes — far fewer than estimates of just two years ago.

Researchers said more than 90 percent of genes associated with disease are identical in humans and mice, underscoring the tremendous value of the mouse in laboratory experiments.

An additional 2.5 percent of each genome, previously discounted as junk, is shared between mouse and human but does not contain the codes for genes. These sections may somehow be important in regulating the function of genes, scientists said.

"There's a lot more that matters in the human genome than we realized," said Massachusetts Institute of Technology biologist Eric Lander, director of the Whitehead Institute.

Comparing the two genomes allows for the quick identification of important regions, because the important regions are the ones most likely to have been preserved in the millions of years since the species diverged.

"These things stand out in high relief. It's like a red flag to scientists that says, `Look at me, come find out what I do,"' said Barbara Wold, a biologist at the California Institute of Technology in Pasadena, who was not connected with the sequencing effort.

The task of comparing and contrasting has led to the discovery of about 1,200 human genes and 9,000 mouse genes.

Scientists hope they will soon complete similar blueprints of the rat, cow, chimpanzee and dog, which will allow even more comparative genomic work.

Identification of a gene does not automatically spell out its function, however. Genetic manipulation of those genes in mice, already commonplace, allows scientists to evaluate their purpose.

Genomic comparisons are expected to shed more light on evolutionary history. Mice, for example, have more genes related to smell and mating than humans do.

"It opens up a whole new era of investigation into the molecular basis of evolution," said Rick Woychik, director of the Jackson Laboratory in Bar Harbor, Maine.

A final version of the mouse genome will take two to three years to complete. The complete human version should be out in April.