Maus doesn't want the way Mendel wants
As a rule, the genome is allocated fairly to the offspring. One portion of the genetic inheritance comes from the mother, the other from the father. But what if you want a little more? Then the additional genetic material can not only inform, but also interfere. Luckily, Gregor Mendel had a green thumb. And he knew how to use it too. In 1866, he succeeded in establishing the rules of heredity named after him with cross-breeding experiments on peas. Mendel explained how the genome of the parent generation is distributed to the offspring during reproduction and recombined in the process. Mendel assumed that the inherited genome would no longer be modified in the growing plants.
Once inherited, according to Mendel, the genes are set in stone. It could have been that easy, but Mendel is betrayed by the plant world. Several decades ago, "paramutation" was observed in the corn plant, a phenomenon in which the genome in the developing plant is modified - in other words, set in stone. In paramutation, one allele, one of the duplicate gene variants, is changed by the other allele. More precisely: allele X is remodeled when it meets allele x at the crossing, it becomes X. The genetic material remains in its building blocks, it is simply packaged differently - the chromatin framework is restructured or individual DNA building blocks are chemically modified.
It's not just the plants that bypass Mendel, the mouse also violates the geneticist's strict rules. François Cuzin from the University of Nice and his colleagues have now discovered a paramutation in a mouse gene, the kit gene. Rodents need this gene in order to be able to fully develop. The scientists determined that the paramutation was not random, but rather targeted, namely during meiotic cell division in the mice, which had originally inherited a functional and a defective kit gene - i.e. the trait combination Kit+/Kit-. Apparently, however, the defective gene somehow initiated the remodeling of the he althy kit gene into the paramuted kit gene - and this happened in almost all mice of the generation. The homozygous mice with this incorrectly modified set of genes did not get away with it completely unscathed. They developed abnormally and had white patches on their feet and at the end of their tails. If Mendel were still alive, he'd probably sit back and be amazed – he'd have to let the paramutation thing sink in first.
Paramutation leads to strange inheritance processes, the researchers showed with their mice: crossed Kit+/Kit- mice produce, completely un-Mendelian, almost exclusively spotted animals. Purely by theory, the he althy kit+/kit+ homozygous mice should not have had spots. Cuzin and his colleagues were able to further narrow down the reason for this: the paramuted state of the kit gene was inherited by the offspring. Surprisingly not in the form of DNA, but in the form of RNA.
The scientists showed that significantly less genetic information could be transcribed into mature messenger RNA by the modified kit gene of the homozygous rodent. In addition, unnaturally large kit RNA molecules had aggregated in the mice. These clusters of RNA were apparently transported into the germ cells of the male and female homozygous mice – the researchers were also able to detect the RNA molecules at least in the sperm. The inherited RNA then somehow interferes in the reading of the intact kit gene in the developing pups, causing less protein to be produced.
The RNA seems to be a quick-change artist in mice: here it is a messenger, a bad inheritance and a disruptor of cell function. Perhaps everything would have turned out differently if the Augustinian monk had turned to the mice. Could the father of genetics have guessed how versatile nature is inheritance?