WHETHER or not some of your genes are active may depend on what food supplements your mother took.
That is the implication of an intriguing study in mice. The coat colour of offspring was changed by simply giving females extra doses of four common nutrients, including folic acid and vitamin B12. The offspring were also less prone to obesity and diabetes than genetically identical mice whose mothers had not been given supplements. The differences were due to heritable changes in the activity of at least one gene in the offspring.
It is not yet clear if the same phenomenon occurs in people. If it does, what women eat during the formation of the egg and early embryo, including supplements, could have an even more profound effect than anyone thought. Changes in gene activity could make their descendants more or less likely to suffer from a range of disorders, including obesity, cancer, diabetes and possibly even autism.
Advertisement
Many people think that there is no downside to food supplements, says the senior researcher, Randy Jirtle of Duke University Medical Center in Durham, North Carolina. “But there could be a lifelong downside and we have no clue yet what those effects are.”
His team’s work establishes the tightest link yet between diet and a strange form of inheritance known as epigenetics: characteristics passed on to offspring that cannot be explained by changes in the DNA sequence. Scientists have long been intrigued by possible epigenetic effects. For example, Dutch women who went hungry during the second world war unsurprisingly gave birth to small babies. These children had normal diets most of their lives, yet when they had children of their own, they too were undersized.
While such cases remain controversial, several mechanisms have since been discovered that can explain epigenetic inheritance. For instance, adding tags known as methyl groups to DNA – a chemical change that does not alter the underlying sequence – can switch off a gene. These methylation marks can be passed to future generations, and experiments in mice have shown that various factors can alter them, including certain drugs, viral infections and the way an embryo is handled during IVF.
Jirtle and his colleague Robert Waterland wondered whether even subtle differences in diet could affect methylation. To find out, they used a mouse strain in which the activity of a gene called agouti, which establishes coat colour, is controlled by the degree of methylation. The more the gene is methylated, the less agouti activity there is and the browner the coat becomes.
The team fed female mice either a normal diet or a diet supplemented with choline and betaine as well as folic acid and vitamin B12. Sure enough, the vitamin-enriched mums were more likely to give birth to pups with browner coats, and chemical analysis showed the agouti gene was more highly methylated (Molecular and Cellular Biology, vol 23, p 5293). Because agouti also affects other aspects of metabolism, the brown mice are less prone to obesity and diabetes.
“It’s a very important result,” says Emma Whitelaw of the University of Sydney in Australia, whose team helped prove that epigenetic effects really can determine an offspring’s traits (91av, 13 November 1999, p 16). “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 any immediate relevance to humans.
While Jirtle’s group plans to look for similar dietary effects in people, Whitelaw points out that the agouti gene is very unusual. It is not clear if there are equivalents in humans, she says.
But Jirtle’s team already has unpublished mouse data suggesting that early nutrition can also alter the methylation of “imprinted genes”. These are genes where one of the two parental copies must be turned off for normal development. Incorrect methylation of imprinted human genes is known to cause certain diseases and can contribute to the development of cancer. If nutrition affects imprinted genes in people, it might even explain the rise in some disorders. “People ask themselves why autism is going up, why asthma is going up,” says Jirtle. “Is something as subtle as this going to be the cause?”