Genomes are so regularly represented as strings of letters—As, Gs, Cs, and Ts—that it’s easy to forget that they aren’t just abstract collections of data. They exist in three dimensions. They are made of molecules. They are physical objects that take up space—a lot of space.
Consider that the human genome is longer than the average human. It consists of around two meters of DNA, which must somehow fit into cells, whose nuclei are about 200,000 times narrower.
So it folds. And it folds in such a way that any given stretch can be easily unfolded, so the genes within it can be read and used. Knots are verboten, and anyone who has ever shoved headphones into their pockets will know how hard it is to scrunch an extremely long thread into a ball without knotting anything.
In the 1970s, biochemists showed that this feat of extreme origami begins when DNA is wrapped around proteins called histones, creating what looks like a string of beads. This reduces the packing problem, but doesn’t come close to solving it. The wrapped DNA must be folded and twisted in ever more complicated (and as yet unknown) ways. Eventually, it forms large loops.
The loops aren’t just a packing solution. They also bring genes into close contact with distant sequences that turn them on or off. So, the 3-D form of the genome also dictates its function. And to really understand how genes are used (and how they are misused in cases of disease), we need to appreciate the genome as a looping, twisting, physical entity, rather than just a string of letters.