Beyond DNA: The Unpredictable Dance of Life
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Your life started with a kiss - between wriggling sperm and ripe egg. But as far as biologists know, nothing in the DNA from either partner determined where on the egg that smacker took place. DNA may be the script of life, but some scenes are largely improvised. A pregnant mother's influence on her baby, the differences between identical twins, and the fleeting liaisons of proteins in a cell all seem to arise without direction from DNA's sequence. Seemingly random biological events can have profound consequences.
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Babies in the womb seem to be particularly open to external influences. A mother's diet and behaviour can profoundly affect a child's future health without altering its DNA sequence, say many researchers, a process called foetal programming. During the Second World War, there was famine in the Netherlands. Mothers who went hungry during early pregnancy had offspring with higher rates of obesity and shorter lives. "There's a real effect that is independent of the DNA sequence that can impact physiology," says Stephen Ford, who studies foetal programming at the University of Wyoming. Poor nutrition at critical points might upset budding organs, says Ford. "The foetus makes compromises so it can survive," he explains. But such compromises might result in a pancreas with less capacity to pump out insulin, laying the foundations of diabetes.
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Rather than DNA dictating our growth and biology, our lifestyle and environment direct the genome. DNA is the molecule with which the rest of biology has to interact. Chemical changes to DNA that switch genes on and off - known as epigenetic changes - are thought to control much of this feedback. For identical twins, differing experiences as embryos or in childhood could flip epigenetic switches, creating variations in appearance, personality or disease risk. A mewing demonstration of this arrived last year in the shape of Cc, the first cloned cat. Cc's DNA sequence is identical to that of her calico-coated mother's - but Cc's fur is a stark black and white. Cc's coat-colour genes may have been activated differently to her mother's, says her creator, Mark Westhusin of Texas A&M University. The epigenetic effects of diet or lifestyle could even underpin inherited conditions.
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So, studying DNA cannot predict our looks and destiny. But surely it can pin down proteins - after all, isn't protein-coding exactly what genes are for? In fact, a DNA sequence tells us remarkably little about the proteins that it encodes. "There are so many aspects of proteins that you can't predict by having access to the genome sequence," says cancer biologist Sam Hanash. Researchers now know that a single gene can create tens or even hundreds of different proteins, according to how the cell reads its genetic information, and how proteins are chopped up or chemically modified. These changes might dictate which other proteins they can partner up with, or where they end up in the cell, for example, a molecule called beta-amyloid precursor protein is produced in at least five different forms.
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Alterations to the protein can lead to disease - again, without any known genetic instruction. When cut by enzymes, some forms of the shortened proteins can clump together and form deposits in the brain that are linked to Alzheimer's disease. Many researchers are attempting to bring order to the chaos by documenting the protein types in key tissues. "Efforts to get to the bottom of proteins will be absolutely humungous," says Hanash.
