PARIS, May 24, 2006 (AFP) - Mutant mice with spotty tails have thrown down the gauntlet to assumptions about heredity.
Experiments by French researchers suggest that RNA, until now seen as a workhorse molecule in animals, can stealthily transport genetic instructions from one generation to the next.
RNA, or ribonucleic acid, is a single-strand molecule that holds genetic code in certain viruses, such as those that cause influenza and AIDS.
Among animals, though, its job is far more modest. It transfers information from DNA - the famous code for making life - and helps make proteins, the stuff of life itself.
A team led by Minoo Rassoulzadegan of the National Institute of Health and Medical Research (Inserm) engineered laboratory mice so that they had a variation in a gene called Kit.
This variation gave the mice white spots on their tails. The mice had a mutant version and a normal version in the two copies of their Kit gene.
The scientists then crossed these mice with others with normal Kit genes.
Of the mice that were born, some had both copies of the normal Kit genes - yet, remarkably, they also had the white spots. In addition, the white spots were transmitted to the next generation of mice, even though these rodents too had the normal genes.
How could this have happened? Under the laws of inheritance, set down in the 19th century by Austrian monk Gregor Mendel, offspring can only get the genetic code exactly as it is handed on from their parents.
By all rights, if the mice both had normal Kit genes, their tails should have been reassuringly spotless.
Rassoulzadegan suggests the answer to this mystery lies in RNA.
The mutant version of Kit produces unexpectedly large numbers of aberrantly sized "messenger" RNA, she found. In addition, the sperm of mutant mice also, surprisingly, was found to have accumulations of RNA.
Intrigued by this, her team injected RNA from mutant cells into normal embryos - and, presto, spotted-tail mice were born.
The hypothesis is that RNA is carried in the mouse's sperm, and at fertilisation it "silences" the activity of the normal Kit gene. This happens not only in the offspring but in subsequent generations too.
"This is the first demonstration of RNA-induced transmission of heredity," Rassoulzadegan told AFP.
Back in 1956, an American biologist called R. Alexander Brink became the first to suggest "paramutation" in which an order issued by one set of genes was remembered in ensuing generations, even though the gene itself was not subsequently handed on in reproduction.
But the phenomenon has only been seen in lab plants, not in mammals. In addition, it occurs only very rarely, apparently as a result of interaction between the two copies of a gene. Normally, the pair of genes operate independently.
In a commentary on Rassoulzadegan's research, also carried in Nature, Paul Soloway of Cornell University, New York, stresses caution, saying that her findings have to be replicated by others before Mendel's rulebook has to be rewritten.
And, he said, the mechanism by which the transmitted RNA works remains unclear.
But if the work is validated, the way is open for a rethink on how RNA could influence the transmision of heredity diseases, metabolism and even types of "imprinted" behaviour from distant generations.
