Cover Story

Debunking junk

"Debunking junk" Continued...

Issue: "Reassessing the genome," Oct. 6, 2012

It suggests a new way to study—and fight—diseases is by looking at the genetic switches associated with them, and learning what makes them flip on or off. Cancer, immune disorders, and even schizophrenia are linked to these various gene switches.

ENCODE researchers haven’t yet learned where all these switches are, or how they might trigger diseases. But their new data provide a roadmap for future investigation.

arrow.jpgThe discoveries of ENCODE are a fulfilled prophecy in the eyes of Stephen Meyer, the director of the Center for Science and Culture at the Seattle-based Discovery Institute, the nation’s leading intelligent design (ID) think tank. Meyer said ID proponents predicted back in the 1990s that much so-called junk DNA would turn out to be functional, and “that’s exactly what’s happened.”

The debate over junk DNA has roots as far back as 1972, when some biologists first used the term junk to describe segments of the genome that didn’t encode instructions for proteins. These segments appeared inactive, just tagging along for a ride in the chromosomes while the protein-coding segments did all the work. With less than 2 percent of the human genome coding for proteins, there seemed to be an awful lot of derelict DNA hanging around.

At the time, few biologists thought noncoding DNA had an undiscovered function. Others “seized on the notion of junk DNA as evidence for Darwinian evolution and against intelligent design—since a designer would presumably not have filled our DNA with so much junk, but centuries of mutations might have,” said by email Jonathan Wells, a senior fellow at the Center for Science and Culture. Wells documents the debate in his 2011 book, The Myth of Junk DNA.

Famed atheist Richard Dawkins, for example, wrote in his influential 1976 work, The Selfish Gene, that noncoding DNA was like a “parasite” within the genome, fulfilling an innate, evolutionary drive to survive in spite of being biologically useless. In subsequent decades, Dawkins and other neo-Darwinists raised the junk argument repeatedly: Why would a creator insert worthless code into a genome? This evolutionary talking point has persisted until today, surprisingly, even though the discoveries of the past decade have shown that less and less of the genome can accurately be described as useless.

So ingrained is the idea of junk DNA that when the ENCODE researchers announced their findings in September, they triggered an immediate academic backlash from critics who said they were “hyping” the data. “The creationists are going to love this,” complained Larry Moran, a biochemist at the University of Toronto, on his personal blog. “This is going to make my life very complicated.”

The critics’ major complaint was the “80 percent” figure: It describes how much DNA researchers found (with some extrapolation) being actively copied to RNA. But that widespread copying doesn’t prove every single piece of RNA is doing something useful in the cell, skeptics said. Much of the copying could be random—and therefore, much DNA might still be “junk” after all.

The debate was vocal enough to prompt a quasi-apology from Birney, the ENCODE organizer, who admitted on his own blog that “we could have used different terminology” to convey the magnitude of the findings. Yet, he insisted that even viewing ENCODE’s findings as conservatively as possible, we should still say at least 20 percent of the genome is actively involved in regulating genes. Some argue the data justifies a higher figure, 50 percent. Either way, the amount is a significant increase from the 2 percent to 5 percent once thought to be important.

The percentage may increase as researchers learn more. Incidentally, Birney thinks further research may show not 80 percent but 100 percent of DNA bases are biochemically active. In the meantime, he recommended his colleagues scuttle the junk DNA term.

arrow.jpgThe more we learn about the human genome, the more astounding its complexity becomes. Multiple dimensions of information encoded in DNA work in unison, offering a staggering array of combinations we barely understand, but which are crucial to the health and traits of each person.

The most basic unit of information, of course, is the adenine-thymine-guanine-cytosine sequence that forms the DNA code itself. A second layer of information involves components of the DNA strand, like histones, spools around which DNA is wrapped. (Chemical modifications to the histones influence DNA’s copy rate.)

Add to that the regulatory switches, constantly governing what portions of DNA should be read and what shouldn’t, dictating what proteins are produced and how genes are expressed. The regulators work differently in different types of cells—a brain cell and muscle cell wouldn’t have the same switches active, for example. (That offers clues to the mystery of how cells know whether to turn into muscle, bone, skin, or kidney.) Some switches are preprogrammed to flip on at certain points in the body’s development, while others might only respond to external stimuli.

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