Always nice to update
Tackling viruses is part of the unfortunate everyday life for cells - sometimes they win, sometimes they lose the fight against the always resourceful invaders. But one thing seems important: in the arms race with new invasion methods, the defense strategists must never stand still. The following applies not only to biologists: Learning from life means learning successful concepts. Mother Nature has been tinkering with the building blocks that make up cells for a few years now. And skillful grabs in the molecular biological toolbox often allow laboratory technicians to make enormous progress faster than if they rely on human engineers who reinvent the wheel for the second time - with comparatively clumsy human technology. Examples are legion of such things cleverly borrowed from the cell machinery, which work specifically in the service of medicine or cell biology.
One example is what is known as RNA interference or RNAi. Nowadays, genes are specifically switched off with it worldwide in order to find out which function they take on. Or more precisely: the proteins produced by the genes are actually removed very selectively. All that is needed for this is to inject a double-stranded RNA (dsRNA) into the cell to be examined – whereby the sequence of the nucleic acid must be identical or very similar to the messenger RNA of the gene to be switched off. As a result, the messenger RNA – and thus the irreplaceable building instructions for the protein to be produced – is completely eliminated by the cell's own cleaning crews. These are somehow stimulated by the injected sequences and instructed in a sequence-specific manner. RNAi now works in laboratories all over the world – nobody really knows exactly why.
Darren Obbard and his colleagues from the University of Edinburgh are looking for answers and are following a path that has been known for a long time: According to the theory, the RNAi mechanism is used in the cells of living organisms to defend against certain viruses. After all, in the common field, forest and meadow cell there is hardly ever a double-stranded RNA - in the normal case - while some viruses can only smuggle their genetic material in the form of short dsRNA into cells to be hijacked. If this is quickly chopped up, it can no longer do any damage.
The RNAi seems to be a method of cell defense against viral invaders - finding proof of this, however, turned out to be difficult. Obbard and colleagues now approached the question from a previously neglected angle. According to her approach, viruses react extremely quickly to changed selection conditions and evolve at an enormous speed. An antivirus program in your host cells can therefore only be successful if it adapts to newly selected virus types just as quickly. And ergo, genes in which the cell's own defenses are encoded should be among the fastest evolving DNA sequences in an organism.
Is that right? Obbard's team tested this on fruit flies, a preferred victim of sigma viruses: Ten to twenty percent of all Drosophila melanogaster in France are infected by this virus. Its genetic makeup is passed on in a double-stranded RNA - and changes it at remarkable speed in order to always be one step ahead of the virus guards of its adversaries.
Exactly those genes that are responsible for the RNAi of fruit flies could definitely keep pace, the researchers found - in fact they belong to the three percent of the fastest evolving gene sequences of fruit flies. The scientists came to this conclusion when comparing the sequences of three RNAi genes from three fruit fly species. Two of these genes – Dcr2 and Ago2 – were so similar in all variants examined that selection mechanisms must have ensured a widespread breakthrough of precisely these variants only very recently.
There is a lot going on with the RNAi defense genes in particular – but not with the structurally related microRNA genes or other hereditary factors in the immune system. The reason for this can actually only be an enormous selection pressure of the viruses, which are evolving just as quickly, the scientists conclude - and so the thesis that RNA interference arose against virus threats is now well documented.
Especially since there are other indications that support it - for example that dsRNA viruses in the arms race seem to develop defensive measures selectively against certain RNAi proteins. It doesn't matter: we wish all endogenous counteracts of the fruit fly cells every success. Incidentally, this may not be necessary in humans, where more sophisticated mechanisms seem to outshine the double-stranded RNA wrecking ball of insects and plants. They kick in as soon as dsRNA gets too close to the cells. Virus scanners for different operating systems are also different in Mother Nature.
