What mothers eat during pregancy could have a fundamental and lifelong effect on the genes of their children, suggests an intriguing new study in mice.
Researchers found they could change the coat colour of baby mice by feeding their mothers different levels of four common nutrients during pregnancy. These altered how the pups' cells read their genes. As a result the mice were also less prone to obesity and diabetes than genetically identical mice whose mothers received no supplement.
The work establishes the tightest link yet between diet and a strange form of inheritance known as epigenetics. Unlike a mutation which changes the DNA sequence of genes, epigenetic factors can alter how a gene is used, while leaving the DNA sequence unchanged.
The mouse study was conducted by Randy Jirtle, at Duke University Medical Center in Durham, North Carolina, and his colleague Robert Waterland. Jirtle says the work belies a "more is better" philosophy about food supplements.
"The rationale is that there is no downside - you can't get too much of this stuff," he says. "But there could be a lifelong downside and we have no clue yet about what those effects are."
One suggested mechanism for epigenetic inheritance is via methylation. A gene can be switched on or off by the adding or removing of carbon tags known as methyl groups to the DNA near a gene.
These are generally set as part of the normal genetic program. But experiments in mice have shown that the tags can be reset by a variety of factors including viral infection or ingestion of certain drugs. Once these new methylation marks are established, they can be inherited by future generations.
To find out is something as simple as components of a regular diet could influence methylation, Jirtle and Waterland used a well known model mouse. In this mouse the activity of a gene called agouti, which establishes coat colour, is controlled by the degree of methylation within the gene. The more the gene is methylated, the more agouti activity decreases and the more brown the rodent's coat becomes.
They fed female mice a normal diet or a diet supplemented with folic acid, vitamin B12, choline and betaine - all nutrients that are used by protein enzymes to create methylation marks.
Sure enough, the vitamin-enriched mums gave birth to pups with browner coats. Because agouti also affects other aspects of metabolism, the browner mice are less prone to obesity and diabetes. Jirtle says his group is planning to look for similar dietary effects on methylation in humans.
"It's a very important result," says Emma Whitelaw of the University of Sydney in New South Wales, Australia who studies epigenetic effects in mice. "It establishes a close link between diet, methylation and gene activity which is going to lead to some interesting experiments."
But she is not convinced the results have an immediate relevance to humans, pointing out that the agouti gene used in the Duke study is somewhat unusual.
Journal reference: Molecular and Cellular Biology (vol 23, p 5293)
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