20080413_A_paradigm_shift_in_genetics.html
Posted on Sun, Apr. 13, 2008
A paradigm shift in genetics
Amanda Gefter
is an editor for New Scientist magazine
(underlining added by blogger)
The struggle between determinism and free will is an ancient one, but genetics seems to have settled the score: "You can't be blamed for your faults," it seems (to some people) to say, "but you're also stuck with the cards you were dealt." ...
"Our understanding of genetics is currently undergoing a paradigm shift," says Melanie Ehrlich, a molecular biologist at the Tulane Cancer Center. "It is now commonly acknowledged among scientists that it is not enough to look to DNA as the sole determinant of heredity."
Ehrlich is referring to the emerging field known as epigenetics. The epigenome is the elaborate chemical switchboard that can turn genes on and off like flipping a light switch. Our genes encode instructions for the building of proteins. On its own, DNA is nothing but an inert biological handbook, but chemicals in each cell actively read and transcribe the instructions, then use them to build our bodies cell by cell. Every cell in your body contains an identical genome, and yet a brain cell is quite different from a skin cell.
How do the differences arise? Because different genes are expressed from one cell to the next. How does a cell know which genes to implement and which to ignore? That set of instructions is contained in the cell's epigenome. Whereas the genome is static - its sequence of base pairs unchanging except in the rare and often detrimental case of a mutation - the epigenome is dynamic, busily deciding which genetic instructions should be put into action and which should be chemically strangled into silence.
Scientists are now learning that the epigenome is highly sensitive to its environment. The food you eat, the air you breathe, and the stress or happiness you feel can actually alter your genetic makeup - not by changing the sequence of your DNA, but by deciding which genes are expressed. ...
Epigenetics is opening up a whole new window on the nature of disease. Many cancers, for instance, are not genetic in origin - caused by one or more mutations to our DNA - but epigenetic. "We finally understand that abnormal epigenetic changes are just as important for cancer formation and development as are genetic mutations," Ehrlich says. "Without epigenetic changes, human cancers would probably be rare." The same is believed to be true for autoimmune diseases, diabetes and depression.
Even more surprising has been the discovery that, like genes themselves, epigenetic effects can be passed down from generation to generation. That was first demonstrated in mammals by Randy Jirtle and colleagues in a groundbreaking experiment in 2000. Jirtle took mice that carried a gene called the agouti gene, which made their fur yellow and rendered them susceptible to particular diseases, and fed them a diet containing so-called methyl groups - molecules that can attach to a gene and block it from being used. The methyl molecules, commonly found in foods such as soy and leafy vegetables, attached to the agouti gene and switched it off.
The real surprise came when the mice became parents. Their offspring were born with the agouti gene still in their DNA but silenced. They had brown fur and were no longer susceptible to the same diseases. The parent mice had passed on not only their DNA, but also the epigenetic switches attached to it. ...
What you eat today could affect your children's genes . . . even your grandchildren's. "What you do now won't affect only you," Jirtle says. "That's not trivial." ...
"The human epigenome remains largely uncharted scientific territory," says Nora Volkow, director of the National Institute of Drug Abuse. ... "It is likely that a human epigenome project . . . may be invaluable in enhancing our understanding of the epigenetic basis of human disease." ...
The epigenetics revolution is in its infancy, but it promises big things - cures for disease, a better understanding of stem cells, even antidotes to aging. From a cultural perspective, it promises to shift the way we think about our own role in our health. Suddenly, free will can be heard shouting over the murmur of genetic determinism. Maybe we aren't stuck with the cards we were dealt after all. You can't un-mutate a gene, but you can potentially reverse an epigenetic effect.
"Epigenetic effects are more flexible and less deterministic, but they require taking more responsibility for the health of your epigenome, for you and for your offspring, even for your grandchildren and great-grandchildren," Jirtle says. "Responsibility is the downside of free will."
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