Rat Gene Maps Show Big Promise

Scientists have published nearly the entire genome of the common rat, making it possible to compare it to the genetic maps of people and mice. That ability is expected to yield clues into evolution and the biology of disease.

The genome of the brown Norway rat — which thrives everywhere from subways to cornfields — is 5 percent smaller in volume than its human equivalent and slightly larger than the mouse.

About 90 percent of its estimated 25,000 to 30,000 genes have counterparts in humans and mice.

Gary Churchill, a senior scientist at the Jackson Laboratory in Bar Harbor, Maine, said having the genetic sequences of two closely related mammals like mice and rats would arm scientists with more genetic information than either would alone, when comparing to humans.

"If you can look at mouse and rat and see that they're the same, you have a much greater likelihood that it's going to be relevant across species," said Churchill, who was not part of the study. "The leap isn't so far."

Other scientists said that, genetically speaking, rats were not simply bigger mice. They predicted the differences between the two rodent species would be valuable, too.

"They are much further apart in evolution than we are from some monkeys," said Ian Jackson of the MRC Human Genetics Unit in Edinburgh, Scotland. "In some respects they are better than mice in behavioral tests. They seem to be smarter. The rat genome should be a great help in tracking down genes that affect behavior."

The research was performed by the Rat Genome Sequencing Project Consortium, and funded by the National Human Genome Research Institute and the National Heart, Lung and Blood Institute. The results appear in Thursday's issue of the journal Nature.

Scientists said all three species probably inherited genes from a common mammalian ancestor about 75 million years ago, not long before dinosaurs became extinct and surviving mammals quickly took their places.

But there are some key differences. For example, the rat relies more heavily on its sense of smell than humans, and it has more genes devoted to scent detection.

The rat genome also contains expanded genes for dealing with toxins and other dangers compared to the mouse genome.

The draft code of the rat is about 90 percent completed, and there are no current plans to finish mapping the rest of the genome, Gibbs said during a news conference Wednesday announcing the rat genome achievement.

Perhaps the most surprising finding is how the rodent lineage evolved faster than primates did, implying that rodent genes are more dynamic and adaptable, said Richard Gibbs, director of the Human Genome Sequencing Center at Baylor College of Medicine and the study's lead author.

In a commentary published in Nature, Kerstin Lindblad-Toh of the Broad Institute/MIT Center for Genome Research said the finding raises questions of whether the mutation rate is different in rodents.

Lindblad-Toh was involved in sequencing the mouse genetic code in 2002.

Since the 1800s, rats have been used as lab models to study human physiology because of their larger size. A century later, mice became in vogue for genetic experiments because they were smaller and easier to breed.

Today, rats are routinely used in drug development to determine the toxicity of drugs before testing on humans and are models to study cancer, diabetes and cardiovascular disease.

With both the rat and genetic codes deciphered, scientists can now choose which of the two animal models is better for studying a particular human disease.

"The decision can now be based on the biology ... rather than what's the technology that's available to study the disease," said Howard Jacob of the Medical College of Wisconsin and co-author of the study. "That is simply a revolution in the way we can practice basic research."

Last year, the National Human Genome Research Institute announced it essentially completed a blueprint of the human genetic code.

By Alicia Chang