One of the central tenets of evolutionary theory is that mutations are random—you can't predict what the next one will be, or when it's going to happen. But it also turns out that mutations are probabilistic. Some of them are a bit more or less likely, depending on the chemistry of the DNA base and its location in the genome.
Now, researchers have identified a mechanism that makes certain types of mutation more probable. This mechanism is a head-on collision between proteins that involves the complex that copies DNA when a cell divides. Because of the mechanics of these collisions, there's a distinct bias towards mutations occurring on one of the two strands of DNA that make up a double helix. The researchers found that this bias is so fundamental that bacterial genes are arranged to take advantage of it, so that some key genes are kept safer from mutations, while others that are key to adaptation can mutate more often.
The problem with collisions arises from the structure of DNA itself. The sugars in the molecule's backbone have a distinctive top (the 5' carbon) and bottom (the 3' carbon). Even in a molecule that's millions of sugars long, every single one of those is oriented the same way. If you move down the strand in one direction, you'll always hit the 5' end first (if you go in the other direction, you'll always hit the 3' end).
This orientation pervades the chemistry of the enzymes that copy DNA, either into a duplicate DNA molecule or into RNA. Every single one that we know about operates in the 5' to 3' direction. (This is thought to be a result of evolution having only managed to make a good copying enzyme once; every one in existence today is just a modified version of that original enzyme.) So, if you started in one place and tried to copy both DNA strands at once, you'd have to send the copying proteins in opposite directions from your start point.
But life doesn't actually do this. In order to coordinate the copying of both strands, one set of copying proteins sets off in the usual direction. But the other DNA strand gets looped around before being fed to a linked enzyme, and copied in small chunks. This may be hard to envision but, conveniently, someone's done the hard work of envisioning it for you.
So, why might this be a problem? The enzyme copying DNA isn't the only thing doing so in the cell—the ones that transcribe it to RNA may be working at the same time. If they're working on the strand that moves in the normal direction, they and the DNA copying proteins will both be heading the same way, which doesn't create much of a problem. But if the transcription proteins are working on the other, looped around strand, the whole complex can slam into it in a head-on collision.
The researchers showed that these head-ons have consequences. They stuck a gene into the chromosome and found that, with the transcription enzymes shut down, mutation rates were identical on both of the two DNA strands. When transcription was switched on, the mutation rate more than doubled. Presumably, the collisions interfere with the proteins copying DNA, causing them to make mistakes more often.
To check the consequence of this, the researchers identified a set of what they called "core genes," which were present in all of the isolates of their bacteria (called B. subtilis) and had very few sequence differences, all of which indicate they perform very important functions. Over 80 percent of these turned out to be encoded on the strand that is less prone to mutations from collisions. The 17 percent left on the other strand? They picked up significant mutations at a rate 43 percent higher than the ones on the safe strand.
If these genes are so important, you may be asking, why are any left on the mutation-prone strand? The authors noticed that the functions of the genes present there tended to be involved in the bacteria's stress response. Being able to adapt more rapidly to changing conditions when under stress can have obvious advantages.
So, overall, it looks like the bacteria's genomes are arranged to optimize a known source of mutations. Most important genes that can't tolerate mutations well are kept on a DNA strand where they're less prone to getting any. The few where changes can be useful are arranged so they suffer mutations more often. It's important to note, though, that this evolutionarily favorable arrangement can be the product of evolution itself. Rearrangements of the genome happen all the time; if any of them happen to be useful, they'll spread through the population. And "useful" can certainly include having a gene avoid (or get) mutations more often.
Nature, 2013. DOI: 10.1038/nature11989 (About DOIs).
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