Battle of Sexes Laid Bare

Minimouse. A normal mouse newborn (left) and a newborn stunted by a lack of IGF-II in the placenta.

A mutant mouse has given scientists the first direct evidence for a theory explaining a rare form of inheritance. A new study supports the theory that so-called genetic imprinting arose as a ploy by males to produce larger offspring and for females to better their chances of giving birth again. The discovery might also provide insight into low birth weight in humans.

A gene is said to be imprinted when proteins are made only from the version inherited from one parent. Although offspring have two copies of each gene, a chemical signal added to genes in sperm or egg prevents one copy from being expressed. The leading explanation is that this gives an evolutionary edge: Fathers activate genes that produce larger offspring, which are more likely to survive; mothers turn on genes for smaller offspring, which consume less energy and leave mothers better able to reproduce in the future. The fact that many of the known imprinted genes--perhaps a few hundred in mammals--are growth regulators supports this idea. But to test the theory directly, one must puzzle out the role of a paternally imprinted gene in the placenta, where mother and fetus fight for nutrients.

Now that test is finally possible, thanks to a new kind of mutant mouse. Geneticist Miguel Constancia and colleagues at the Babraham Institute in Cambridge, U.K., created mice with placentas that can't make insulin-like growth factor II (IGF-II). Normally, the gene for IGF-II is paternally imprinted so that the fetus will grow fast. But when Constancia knocked out a stretch of DNA that controls expression of IGF-II, newborn mice were 33% smaller than normal newborns. And the mutant fetuses received 25% less nutrients via the placenta, the researchers report in the 27 June issue of Nature. That suggests that the gene normally promotes larger offspring--thanks to dad's imprinting.

The study is excellent evidence that imprinting results from the evolutionary tug of war between the sexes, says Gudrun Moore, a molecular biologist at Imperial College, London. Imprinted genes might be a major cause of low birth weight and its many associated health problems in humans, says Randy Jirtle, a molecular biologist at Duke University in Durham, North Carolina. That's because only one copy of imprinted genes is available. "It's like you're flying a two-engine plane," he says. "If one engine goes out, you can still fly, but you feel uncomfortable."

Related sites
Babraham Institute Imprinting Research
Randy Jirtle's site

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