Fuente: REALscience
Expuesto el: lunes, 10 de septiembre de 2012 19:13
Autor: Michael Bradbury
Asunto: Junk DNA Finally Has a Purpose
| If the human genome is the computer of our cells then newly discovered gene switches are the operating system. When the Human Genome Project finished sequencing the book of life 12 years ago, biologists thought we had the three-billion letter code to understand how we all operate. But that book turned out to be harder to read than we thought.
Dr. John Stamatoyannopolous, University of Washington Genomicist and Member of ENCODE Consortium One of the results that surprised scientists was that there were only about 20,000-25,000 genes in the entire genome. That comprises about two to three percent of DNA, leaving the vast majority unexplained. At the time, scientists called the remaining pieces of the genome “Junk DNA.” Now they are discovering that the junk holds an important purpose. Much of the inexplicable DNA in the human genome helps regulate those 22,000 or so genes. These regulatory switches may be responsible for the course that diseases take to develop. Through an international genetic effort called the ENCyclopedia Of DNA Elements (ENCODE) Project scientists from around the world announced a big update to the story of the human genome. British computational biologist Ewan Birney, a lead investigator on the ENCODE project says, “In 2000, we published the draft human genome and, in 2003, we published the finished human genome and we always knew that was going to be a starting point. We always knew that protein-coding genes were not the whole story.”
DNA Double Helix Contains Genes and Biochemical Switches to Regulate Genes Through their work, scientists have found that 18 percent of human DNA helps regulate the two percent of DNA involved in coding for proteins. The ENCODE researchers say that about 80 percent of the genome has some biochemical function. Just after the Labor Day holiday last week, a batch of over 30 scientific papers spread across the journals Science, Nature, Genome Biology, Genome Research and Journal of Biological Chemistry provided a different view of the same finding — that so-called junk DNA serves an important regulatory function. Genes don’t operate in isolation. Especially in rare diseases, hundreds of genes are at work and regulatory elements associated with the genes switch genes on and off. Stanford University’s Mike Snyder says, “Much of the difference between people is due to the differences in the efficiency of these regulatory elements. There are more variants, we think, in the regulatory elements than in the genes themselves.” In fact, the 440 ENCODE scientists found 10,000 new “genes” that code for components that control how the more familiar protein-coding genes work. They found 70,000 promoter regions, sites adjacent to genes where proteins bind to control gene expression. And they discovered nearly 400,000 enhancer regions that regulate expression of distant genes. But Birney says there is still a long way to go. Right now only about half of the regions are mapped and the researchers are only about one-tenth of the way to understanding how the genome operates on a deeper level. Bruce Stillman, president of Cold Spring Harbor Laboratory, which played a big role in the project tells NBC News, “This has opened up whole new galaxies. It’s like having a bigger telescope.” When the full human genome was sequenced in 2003 scientists realized that the 22,000 genes they discovered didn’t explain the complexity of humans. After all, many animals had more genes than people. And far more than rice, which has at least 50,000 genes. Genomic experts realized that there was more to the story but didn’t have the answers. That’s when the Human Genome Project switched gears into the ENCODE Project. Eric Green, director of the National Human Genome Research Institute says, “We understood precious little about the processes that turns genes on and off. In short we had more questions than answers about how the human genome works.” Now years later, they have discovered 40 million switches that control genes, turning them on and off and up and down in complex and subtle ways. John Stamatoyannopouloss from the University of Washington says, “The genome is loaded with gene controlling switches. There are literally millions of these.”
ENCyclopedia Of DNA Elements Project, Next Phase of the Human Genome Project National Institutes of Health director Francis Collins called the discovery “awesome and elegant.” He tells NBC News, “This is the first truly comprehensive view of how the three billion letter instruction book for human biology actually carries out its work, across many tissues and over the course of development.” And this discovery could change the field of biotechnology, which has largely moved away from genomics in favor of more traditional methods for developing drugs to fight disease. Snyder says many common diseases, like heart disease, cancer, and allergies, are likely controlled in the switches not the genes themselves. Scientists who thought gene mutations were the cornerstone for disease development now believe they may only be directly associated with rare diseases. The new data from the ENCODE project will help doctors diagnose diseases, predict which treatments will work best and allow them to monitor patients’ progress. Besides disease detection, understanding these gene switches could also shed light on non-disease traits such as height, weight and expected life span. And it helps explain why we can share 98 percent of our genes with chimpanzees yet remain so different. Stamatoyannopoulos says, “Genes occupy only a tiny fraction of the genome, and most efforts to map the genetic causes of disease were frustrated by signals that pointed away from genes. Now we know that these efforts were not in vain, and that the signals were in fact pointing to the genome’s ‘operating system’ — the instructions for which are hidden in millions of locations around the genome.”
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