Intricate Toiling Found In Nooks of DNA Once Believed to Stand Idle

The teams targeted 44 areas along the genome, half of them already of interest and half chosen at random to include gene-dense "urban" areas and expanses of seemingly inactive genetic "desert."

Perhaps most surprising was how much of the human genome is at work at any given time, the scientists said.

Researchers have long known that only about 2 percent of human DNA is involved in making proteins, the molecular workhorses inside cells. That involves a two-step process in which a stretch of DNA -- a gene -- serves as a template to produce a strand of RNA, which is then used as a template to produce a protein.

Recent studies had shown that some snippets of DNA between genes also are transcribed into RNA even though they do not go on to make proteins. Surprisingly, though, the new work shows that most of a cell's DNA gets transcribed, raising questions about what all that RNA is doing.

Some of it may be doing nothing. "It may be like clutter in the attic," Collins said, noting that clutter could be useful when conditions change and evolution needs new material to work with.

But much of it seems to be playing crucial roles: regulating genes, keeping chromosomes properly packaged or helping to control the spectacularly complicated process of cell division, which is key to life and also is at the root of cancer.

"We are increasingly being forced to pay attention to our non-gene DNA sequences," John M. Greally of the Albert Einstein College of Medicine in New York wrote in a commentary in today's issue of the journal Nature, where one of the new reports is being published. The 28 other papers appear in today's issue of Genome Research.

Greally noted that several recent studies have found that people are more likely to have Type 2 diabetes and other diseases if they have small mutations in non-gene parts of their DNA that were thought to be medically irrelevant.

Another aspect of Encode had researchers looking at the equivalent 1 percent of the genomes of more than 20 other mammals, and those results are forcing them to rethink the interplay between genetics and evolution.

The expectation was that many of the most active DNA sequences in humans would be prevalent in other mammals, too, because evolution tends to save and reuse what works best. But more than half were not found in other creatures, which suggests they may not be that important in people, either, said Ewan Birney of the European Bioinformatics Institute in Cambridge, England, a coordinator of the Encode effort.

"I think of them as gate-crashers at a party," Birney said. "They appeared by chance over evolutionary time . . . neither to the organism's benefit nor to its hindrance. That is quite an interesting shift in perspective for many biologists."

Although the new view of the genome may at first complicate efforts to identify DNA stretches of prime medical interest, Encode is sure to help in the long run, said Michael Snyder of Yale University, another coordinator.

"Defining the functional elements helps us zoom in to look for differences in sequence that might relate to disease," he said.