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Unformatted text preview: DNA IS NOT DESTINY Back in 2000, Randy Jirtle, a professor of radiation oncology at Duke University, and his postdoctoral student Robert Waterland designed a groundbreaking genetic ex- periment that was simplicity itself. They started with pairs of fat yellow mice known to scientists as agouti mice, so called because they carry a particular gene—the agouti gene—that in addition to making the rodents ravenous and yellow renders them prone to cancer and diabetes. Jirtle and Waterland set about to see if they could change the unfortunate genetic legacy of these little creatures. Typically, when agouti mice breed, most of the offspring are identical to the parents: just as yellow, fat as pincush- ions, and susceptible to life-shortening disease. The par- ent mice in Jirtle and Waterland’s experiment, however, produced a majority of offspring that looked altogether dif- ferent. These young mice were slender and mousy brown. Moreover, they did not display their parents’ susceptibility to cancer and diabetes and lived to a spry old age. The ef- fects of the agouti gene had been virtually erased. Remarkably, the researchers effected this transforma- tion without altering a single letter of the mouse’s DNA. Their approach instead was radically straightforward— they changed the moms’ diet. Starting just before concep- tion, Jirtle and Waterland fed a test group of mother mice a diet rich in methyl donors, small chemical clusters that can attach to a gene and turn it off. These molecules are com- mon in the environment and are found in many foods, in- cluding onions, garlic, beets, and in the food supplements often given to pregnant women. After being consumed by the mothers, the methyl donors worked their way into the developing embryos’ chromosomes and onto the critical agouti gene. The mothers passed along the agouti gene to their children intact, but thanks to their methyl-rich preg- nancy diet, they had added to the gene a chemical switch that dimmed the gene’s deleterious effects. “It was a little eerie and a little scary to see how some- thing as subtle as a nutritional change in the pregnant mother rat could have such a dramatic impact on the gene expression of the baby,” Jirtle says. “The results showed how important epigenetic changes could be.” Our DNA—specifically the 25,000 genes identified by the Human Genome Project—is now widely regarded as the instruction book for the human body. But genes them- selves need instructions for what to do, and where and when to do it. A human liver cell contains the same DNA as a brain cell, yet somehow it knows to code only those proteins needed for the functioning of the liver. Those in- structions are found not in the letters of the DNA itself but on it, in an array of chemical markers and switches, known collectively as the epigenome, that lie along the length of the double helix. These epigenetic switches and markers in turn help switch on or off the expression of particular genes. Think of the epigenome as a complex software genes....
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- Summer '11
- DNA, DNA methylation, epigenetic changes, Randy Jirtle