A few of our about 30,000 genes are absurdly long, perhaps a tenth of a mm of DNA for a single gene. This is pretty long, the genes are in a nucleus less than a hundreth of a mm across, i.e., ten times smaller than one of these genes stretched out to its full length. These genes need to be transcribed into RNA that in turn makes the protein. The RNA molecule is itself just a big. It is a bit of a mystery how such huge molecules are made and manipulated in such a tight-fitting environment, but the fact I am alive, and that you are alive, is testament to the fact that it clearly works.
But a paper in Nature a couple of weeks ago suggests that these genes only fully function when they have help. This help is provided by wonderful molecules called topoisomerases. Topoisomerases unwind DNA. Above a picture of a Mobius strip, which is made from a piece of paper that is twisted once and then one end of the strip is attached to the other. It is impossible to unwind a Mobius strip, i.e., to unwind it into a normal unwound cylindrical loop of paper, without cutting it. What applies to paper strips applies exactly to DNA. DNA which is twisted like the Mobius strip cannot be unwound without cutting it. This is what topoisomerases do, they cut the DNA, unwind it and then stick it back together. A cute demonstration of geometry in action, and essential to all life on Earth.
All this has been known for years, what is new is that King and coworkers show that if they inhibit topoisomerases, then the very long, but not shorter genes, are less active – make less protein. Naively, it looks like topoisomerases are needed to keep DNA from getting too tangled when these genes are active. This in itself is cute.
Even more interesting is that a lot of these very long genes are implicated in autism. The hypothesis is that a mutation in the gene for a topoisomerase could make the topoisomerase less active and so make a whole set of long genes less active and these less active genes would predispose the person to autism. An interesting idea, that a predisposition to autism could be due to tangled genes.
