We Have Little Idea What's Going On Down There, But We Know For Sure How It Came To Be!

Boston Globe:

The science of life is undergoing changes so jolting that even its top researchers are feeling something akin to shell-shock. Just four years after scientists finished mapping the human genome - the full sequence of 3 billion DNA "letters" folded within every cell - they find themselves confronted by a biological jungle deeper, denser, and more difficult to penetrate than anyone imagined.

"Science is just starting to probe the wilderness between genes," said John M. Greally, molecular biologist at New York's Albert Einstein School of Medicine. "Already we're surprised and confounded by a lot of what we're seeing."

A slew of recent but unrelated studies of everything from human disease to the workings of yeast suggest that mysterious swaths of molecules - long dismissed as "junk DNA" - may be more important to health and evolution than genes themselves.

Meanwhile, a tricky substance called RNA - for decades viewed as the lowly "messenger boy " for genes and proteins - turns out to be a big league player in cell function. It may even represent the cell's command and control system, according to its more vigorous proponents.

In any event, lots of basic biological beliefs are going out the window these days as new discoveries come so rapid-fire that the effect is almost more disorienting than illuminating.

The discoveries have one common theme: Cellular processes long assumed to be "genetic" appear quite often to be the result of highly complex interactions occurring in regions of DNA void of genes. This is roughly akin to Wall Street waking to the realization that money doesn't make the world go 'round, after all.

"It's a radical concept, one that a lot of scientists aren't very happy with," said Francis S. Collins, director of the National Human Genome Research Institute. "But the scientific community is going to have to rethink what genes are, what they do and don't do, and how the genome's functional elements have evolved.

"I think we're all pretty awed by what we're seeing," Collins said. "It amounts to a scientific revolution."

For half a century, the core concept in biology has been that every cell carries within its nucleus a full set of DNA, including genes. Each gene, in turn, holds coded instructions for assembling a particular protein, the stuff that keeps organisms chugging along.

As a result, genes were assigned an almost divine role in biological "dogma," thought to govern not only such physical characteristics as eye color or hair texture, but even much more complicated characteristics, such as behavior or psychology. Genes were assigned blame for illness. Genes were credited for robust health. Genes were said to be the source of the mutations that underlay evolution.

But the picture now emerging is more complicated, one in which illness, health, and evolutionary change appear to be the work of almost fantastical coordination between genes and swaths of DNA previously written off as junk.

The idea that genes possess a singular supremacy took a knock when the human genome was fully sequenced in 2003, revealing that only about 1.5 percent of our DNA consists of actual genes coding for protein.

Another 3.5 percent of DNA is of gene-linked regulatory material whose function isn't well grasped, but which is recognized as vital because it has been precisely duplicated in living things for hundreds of millions of years. "That's smoking gun evidence that nature cares about this stuff," said Eric S. Lander, director of the Broad Institute, a research center affiliated with MIT and Harvard that focuses on applying genomics to medicine.

As for the remaining 95 percent of the genome? "There's this weird lunar landscape of stuff we don't understand," Lander said. "No one has a handle on what matters and what doesn't."

Until recently, the rest of the genome - the murky regions between individual genes - was viewed as occupied by more or less useless glop. Noncoding DNA is the polite term for junk DNA.

But the glop is starting to look like gold. And genes, in a sense, are losing some of their glitter.

"To our shock and consternation, we're learning how little we know about the parts of the genome that may matter most," said Dr. David M. Altshuler, associate professor of genetics and medicine at Harvard Medical School and also a top researcher at the Broad Institute.

"Maybe some of it really is junk. Maybe most of it is junk," he said. "But one shouldn't bet against nature. Maybe it all serves some sort of a purpose. We really don't know."

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