For the past 50 years, scientists have been trying to unravel the mystery of an unorthodox genetic effect: In some species, a gene from one parent turns off the analogous gene from the other. A new study of the phenomenon--called paramutation--may have finally elucidated how this works.
A team led by molecular biologist Vicki Chandler of the University of Arizona in Tucson looked at a gene known to determine the color of a corn stalk. One version of this gene, called B-Intense (B-I), produces a purple pigment. But if B-I gets paired up with another version of the gene, called B', B-I is silenced and produces very little pigment--resulting in a mostly green stalk. The effect is heritable: B-I stays turned off in the next generation, even if B' is no longer there. In earlier work, Chandler and her coworkers had found that this paramutation effect required the action of a second gene, called mediator of paramutation1 (mop1), although it was unclear what this gene did. So the team isolated and sequenced mop1 and then looked for clues to its function by comparing it with similar genes in other plants.
In the 20 July issue of Nature, the team reports that mop1 is very similar to a gene found both in rice and a relative of the mustard plant. In those plants, the gene codes for an enzyme called RNA-dependent RNA polymerase (RDRP), which makes copies of RNA molecules. Both B-I and B' contain a short section of DNA repeated seven times, and in the new study, Chandler and her colleagues conclude that RDRP replicates RNA transcribed from these repeats. Because there are more of these repeats in B-I and B' than in other versions of the gene (which do not experience paramutation), more of these RNA molecules are produced. Once the RNA reaches a certain threshold level, the authors suggest, it can silence the B-I version of the gene. Indeed, evidence that RNA can silence genes has been found in other organisms, including mice, in which paramutation was also demonstrated recently (ScienceNOW, 24 May).
The results could "revolutionize future work into understanding the mechanism of paramutation in plants and ... mammals," says Shiv Grewal, a molecular biologist at the National Cancer Institute in Bethesda, Maryland. Still, he adds that while the mechanism proposed by the authors is plausible, others should also be considered.