Subtle-But Important-Functions of Junk-DNA - Evolution News & Views

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Subtle-But Important-Functions of Junk-DNA

The December 17, 2010 issue of Science has yet another article explaining why the concept of "junk"-DNA should no longer be given much credence:

It used to seem so straightforward. DNA told the body how to build proteins. The instructions came in chapters called genes. Strands of DNA's chemical cousin RNA served as molecular messengers, carrying orders to the cells' protein factories and translating them into action. Between the genes lay long stretches of "junk DNA," incoherent, useless, and inert.

That was then. In fact, gene regulation has turned out to be a surprisingly complex process governed by various types of regulatory DNA, which may lie deep in the wilderness of supposed "junk." Far from being humble messengers, RNAs of all shapes and sizes are actually powerful players in how genomes operate. Finally, there's been increasing recognition of the widespread role of chemical alterations called epigenetic factors that can influence the genome across generations without changing the DNA sequence itself.

(Elizabeth Pennisi, "Shining a Light on the Genome's 'Dark Matter'," Science, Vol. 330 (6011):1614(December 17, 2010).)

The quote is intriguing because it suggests that the importance of noncoding-DNA to an organism might not always be readily apparent. Indeed, the article goes on to state that mutations in noncoding DNA can increase the risk of disease later in the life of the organism:

Further evidence that noncoding DNA is vital has come from studies of genetic risk factors for disease. In large-scale searches for single-base differences between diseased and healthy individuals, about 40% of the disease-related differences show up outside of genes.
This could challenge a common argument in favor of "junkiness" for noncoding DNA. In particular, some ID critics have cited studies where stretches of noncoding DNA were removed from mice, and it was claimed that the mice still develop and survive. Does that mean non-coding DNA is useless junk after all? Not if the noncoding DNA has important long-term effects, such as preventing disease in the organism.

As seen in the above statement from the Science article, noncoding DNA can have important functions in an organism apart from initial growth and development. Thus, researchers are finding that mutations in noncoding DNA can increase the risk of disease over an organism's lifetime.

Indeed, when commenting on a study that tried to remove noncoding-DNA from mice, principal researcher Barbara Knowles acknowledged that noncoding DNA might have subtle functions that aren't immediately apparent:

Knowles cautions that the study doesn't prove that non-coding DNA has no function. "Those mice were alive, that's what we know about them," she says. "We don't know if they have abnormalities that we don't test for."

David Haussler of the University of California, Santa Cruz, who has investigated why genetic regions are conserved, says that Rubin's study gives no hint that the deleted DNA has a function. But he also believes that non-coding regions may have an effect too subtle to be picked up in the tests to far.

"Survival in the laboratory for a generation or two is not the same as successful competition in the wild for millions of years," he argues.

(Roxanne Khamsi, "Mice do fine without 'junk DNA'," Nature (October 20, 2004).)

Likewise an article at MSNBC noted that mice could survive without certain stretches of "junk" DNA, but that DNA was "ultraconserved" across different species of mammals, hinting at function:

The researchers call these mystery snippets "ultraconserved regions," and found that they are about 300 times less likely than other regions of the genome to be lost during the course of mammalian evolution. ... The fact that these segments haven't been weeded out by natural selection implies that they serve an important function in mammals. Yet mice in the lab bred to lack four of these DNA strands appear healthy and don't seem to be missing any vital genes.

Wondering if the odd results were simply some fault of the lab experiment, and perhaps the mice really weren't as well off as they seemed, the researchers investigated whether any other mammals were also blithely living without these regions.

Amazingly, they found that was not the case. The researchers compared ultraconserved sequences of at least 100 base pairs shared by humans, macaques and dogs with the DNA of rats and mice. They found that less than one-tenth of 1 percent of the segments shared among the primates and dogs were missing in the rodents. ... "What's striking about this research is that [the regions] really are almost never lost," Bejerano told LiveScience. "You're asking if a species can live without these regions, and the resounding answer from our paper is that they seem to have an effect that is strong enough that evolution would weed [individuals without the regions] out of an evolving population."

... Scientists have some guesses about what these strange segments might be used for. Perhaps these DNA strands actually code for multiple layers of information, Bejerano suggested. In that case, each layer could be redundant, with other segments serving the same purpose in other contexts, but together they provide a vital backup system.

Or, they could be crucially important, but only at specific times in a species' history.

"Imagine that these regions somehow protect you from a disease that only strikes the population every once in a while," Bejerano said.

If tweaking non-coding DNA increases the risk of certain diseases, then it would seem that noncoding DNA can have precisely the sort of subtle effects that these scientists are talking about.