The Unseen Genome.doc - The Unseen Genome Gems among the...

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The Unseen Genome: Gems among the Junk By W. Wayt Gibbs Scientific American, November, 2003 Just when scientists thought they had DNA almost figured out, they are discovering in chromosomes two vast, but largely hidden, layers of information that affect inheritance, development and disease About 20 years ago astronomers became convinced that distant galaxies were moving in ways that made no sense, given the laws of gravity and the fabric of celestial objects visible in the sky. Gradually they were forced to conclude that the universe is not as empty as it appears, that in fact it must be dominated by some dark kind of matter. Although no one knew what the stuff is made of or how it works, scientists could see from its effects that it is out there. The quest to understand dark matter (and more recently, dark energy) meant revising or replacing theories, but it reenergized astrophysics and cosmology. A similar revelation is now unfolding in molecular genetics. This year biologists celebrated the 50th anniversary of the discovery of the double helix, and the Human Genome Project announced its completion of a "final draft" of the DNA sequence for Homo sapiens. Scientists have clearly mastered DNA in the lab. Yet as they compare the DNA of distantly related species and look more closely at how chromosomes function in living cells, they are increasingly noticing effects that current theories cannot explain. Journals and conferences have been buzzing with new evidence that contradicts conventional notions that genes, those sections of DNA that encode proteins, are the sole mainspring of heredity and the complete blueprint for all life. Much as dark matter influences the fate of galaxies, dark parts of the genome exert control over the development and the distinctive traits of all organisms, from bacteria to humans. The genome is home to many more actors than just the protein-coding genes. The extent of this unseen genome is not yet clear, but at least two layers of information exist outside the traditionally recognized genes. One layer is woven throughout the vast "noncoding" sequences of DNA that interrupt and separate genes. Though long ago written off as irrelevant because they yield no proteins, many of these sections have been preserved mostly intact through millions of years of evolution. That suggests they do something indispensable. And indeed a large number are transcribed into varieties of RNA that perform a much wider range of functions than biologists had imagined possible. Some scientists now suspect that much of what makes one person, and one species, different from the next are variations in the gems hidden within our "junk" DNA. Above and beyond the DNA sequence there is another, much more malleable, layer of information in the chromosomes. "Epigenetic" marks, embedded in a melange of proteins and chemicals that surround, support and stick to DNA, operate through cryptic
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codes and mysterious machinery. Unlike genes, epigenetic marks are routinely laid down, erased and rewritten on the fly. So whereas mutations last a lifetime, epigenetic
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