A team of scientists have found evidence that RNA in the sperm of mice is able to transmit a trait that is not coded for in the animal's DNA. The team, working at the University of Nice, France, were studying a gene called Kit. This gene occurs in either a normal or mutated form, but if two mutated copies are inherited the animals die shortly after birth. Animals that are heterozygous for the gene - having one normal copy and one mutated - survive but have white patches. According to the laws of typical Mendelian inheritance, when crossing heterozygous animals, those that inherit two copies of the normal gene should be entirely normal - however, in the case of Kit, 24 out of 27 mice that inherited two normal copies of the gene still, inexplicably, had white patches.
RNA usually acts as a type of 'go-between' that translates genes into proteins which cause an external effect. In this case, however, it appears that mutant RNA from the heterozygous father can accumulate in sperm, which then causes the white patches to occur on the mice. The mutant Kit gene manufactures lots of odd-shaped, unusually small RNA molecules. These molecules build-up in the animal's tissues - including sperm - and it is this which is thought to have caused the effect in the offspring. The team tested this hypothesis by extracting the abnormal RNA from mutant cells and injecting it into very early mouse embryos. This caused the new - genetically normal - animals to develop white patches. The researchers think that the mutant RNA molecules act to 'silence' Kit gene activity in the offspring, even in the absence of the mutant version.
Paramutation - where a genetic characteristic is 'remembered' in future generations even where the particular version of the gene is no longer present, is known about in plants but this is the first time it has been shown in animals. Experiments showed that the effect could be mediated by either the mother or father - the researchers chose to look at sperm as sperm cells are relatively easier to study than eggs. They also found that the effect could last for a number of generations. The team acknowledge that further research needs to be done to firmly establish the underlying processes but it does lead to the exciting possibility that RNA transfer may mediate other so-called epigenetic effects, for instance certain behaviours or metabolism traits. The Nice team next plans to look for other mouse characteristics that may be mediated through transfer of RNA. Minoo Rassoulzadegan, lead author of the paper said, 'this brings valuable information about modification of our genome, and perhaps this research may eventually help us to understand why we are all so different from each other'.