Published Tuesday, July 11, 2000, in the San Jose Mercury News 'Nonsense DNA' mystifies geneticists Genome challenge: to understand bits of random coding BY SETH BORENSTEIN Mercury News Washington Bureau WASHINGTON THE HUMAN genome, the 3.15 billion-letter instruction book for our cells, seems pretty elegant. But it turns out to be chock-full of typos, gibberish, repetitions and redundancies, and scientists don't know why. "Junk DNA," some call the residue, and it takes up an amazing 97 percent of our genome. So the recent announcement that the human genome was fully mapped is tempered by a monumental mystery: What is this so-called junk doing in our DNA? It's suddenly a hot topic in genomics, splitting the field into scientists who think the mystery material is useless and those who say it has some not- understood-but-vital purpose. Stuff of controversy "This is something we tend to talk a lot about after we've had a lot of said Rick Wilson, professor of genetics and co-director of the Genome Sequencing Center at Washington University in St. Louis. "You want to believe that the system is designed to be as efficient as possible. So why does it have all this other stuff?"
"I think of it as the comparison of trash and junk," said Roy Britten, the California Institute of Technology biologist who's the "father" of junk DNA. "Trash you throw away. Junk you keep in case it may be useful." The DNA that gene-mapping scientists study is called a coding sequence. It instructs a cell to build a particular protein. Proteins, which do most of the work in cells, can serve a structural purpose, such as forming collagen fiber, or cause a chemical reaction, such as metabolizing a nutrient. But the DNA needed to produce the proteins that do all the cell's work amounts to only 3 percent to 5 percent of the human genome, biologists say. "There's a lot more going on than that," said Ken Dewar, a research scientist at the Massachusetts Institute of Technology's Whitehead Institute in Cambridge, Mass. The rest of the genome is technically called non-coding, or, because it gets in the way of decoding, "nonsense."
Cells themselves delete it when they reproduce DNA. Scientists say there are two major types of junk DNA. One is expressed as a repetitive sequence that keeps popping up in the DNA strand. "For the life of me, I can't figure out why it's anything like a benefit" to have all these repetitions, said Steven Scherer, director of mapping at Baylor College of Medicine's Human Genome Sequencing Center in Houston. The other type of junk is the intron, a seemingly random repetition in the middle of real protein instructions. It's as if in this sentacgtcaaagtcaaaence, the letters "acgtcaaagtcaaa" were stuck in the middle of the word "sentence." When the DNA replicates, the cell edits out the "acgtcaaagtcaaa" and just copies the word "sentence." "The cell has to go to a lot of trouble because the introns are there," said Rex Chisholm, professor of cell and molecular biology at Northwestern University in Chicago. Introns seem tied to evolution, Chisholm said.
The more highly evolved species, such as humans, tend to have more and longer introns than less- evolved life forms, such as yeast. And many of the genetic differences between species occur in introns. For example, chimpanzees and humans are about 1.6 percent different in their junk DNA, but only 0.5 percent different in their protein-building instructions, said Morris Goodman, professor of anatomy and cell biology at Wayne State University in Detroit. Scientists who think of non-coding DNA as garbage simply say that cells are inefficient. Junk DNA, especially introns, may have been relevant in earlier evolutionary stages or it could have been a harmless mistake. "They are not useful and also not very harmful," said Rudolf Raff, director of the Indiana Molecular Biology Institute in Bloomington. Raff compares the junk DNA to someone adding empty file folders with blank paper to a filing cabinet. "It doesn't matter, and that's the way I think our genome is to a large part," he said. A hidden purpose?
Others think it has a purpose that hasn't been discovered. "I don't think there's anything that's junk DNA," said top government genomics researcher Ari Patrinos, associate director for biological and environmental research at the Department of Energy. We just don't know the use for it, he said. "For us to be arrogant about making presumptions about what is and what isn't necessary is pretty human." So the push is to find out what this stuff does. Scientists theorize that stretches of junk DNA could be space holders in the genome or spare parts that become useful in mutating DNA. Early research is finding that when the seemingly nonsense parts of DNA are removed, cells multiply a bit, but don't function as well as they do with full- length genomes. This is why biologists who have mapped the human genome are only on "the beginning of a wonderful voyage," Patrinos said. "The clicks and whirs of the human cell, it's a fascinating mechanism. The reality is, we don't understand much of it." [Source: http://www7.mercurycenter.com/premium/scitech/docs/junkdna11.htm ]
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