The idea of the “selfish gene,” made famous by Richard Dawkins nearly 40 years ago, was instantaneously controversial. It invigorated a sometimes-rancorous discussion of the focus of natural selection, with Dawkins and others arguing that the gene is the thing on which natural selection ultimately acts. The debate is ongoing and always entertaining. I think the real strength of the selfish gene concept is not so much that it acts as a bona fide theory of evolutionary mechanisms, but that it presents a truly useful view of how evolution often works. The gene’s eye-view that Dawkins adopts is particularly helpful when we encounter genes and interactions for which the word ‘selfish’ seems clearly apt.
Biology has described many interesting examples of genes behaving badly, acting in ways that admit no other explanation than that provided by the metaphor of a “selfish replicator.” Dawkins provides some nice examples in The Selfish Gene and in its superior but more technical sequel, The Extended Phenotype. One really interesting example comes from the world of yeasts, in a story that has provided an explanation for one of the biggest mysteries of yeast biology. Part I is about the new example, and Part II is about how a selfish replicator explained that big mystery.
Part I: AT-AT = destruction
The story begins with the discovery (decades ago) of some virus-like parasites that plague various groups of fungi (yeasts). These parasites are virus-like in that they are small bits of DNA or RNA that rely on hosts for survival and propagation, and they’re often called viruses even though they don’t usually make a vehicle to travel around in. The parasites in this story are called “killer elements” for good reason. They are pieces of DNA that enable the host cell to make a toxin that can kill neighbouring cells. The package deal includes a gene for making the toxin and a gene that makes the host cell immune to the toxin. A yeast cell without the killer element is susceptible to the toxin, whereas a cell carrying the element is able to kill without being harmed itself.
At first, this looks like a pretty good deal for the host—as long as its children carry the element, it can kill competitors indiscriminately. But it does come at a cost, since the host must make at least two proteins (the toxin and the immunity protein), and it’s easy to picture how the yeasts would cheat: they would grab the gene for immunity and insert it permanently into their genetic endowment. If it were that simple, we would expect the immunity gene to spread rapidly through a population and become permanent in the species (or population). But this is uncommon. Why?
Amazingly, some of these killer elements have made it effectively impossible for a yeast cell to cheat by permanently installing the immunity gene. A new paper in PLOS Genetics explains how it works, and an accompanying piece discusses how the logic of the system could be widespread in biology.
The authors (Kast et al., a collaborative group from two institutions in Germany) were working on a DNA-based killer element that lives in the cytoplasm (meaning outside the nucleus, and that’s important here) and is passed on to other cells by normal reproduction. The toxin and the immunity protein are fairly well understood. But there is something strange about the immunity gene. It works fine, and generates immunity, as long as it lives in the cytoplasm. (This makes it a plasmid, in technical terms.) But if the gene is moved into the nucleus (by an experimenter), it doesn’t work at all. The strategy (on the part of the killer element) is brilliant and selfish—cells can’t separate the immunity gene from the rest of the killer element, which can only exist as a package deal. But how does this work? After all, DNA is DNA. How does this particular gene suddenly go silent when it’s put into the place where all normal yeast genes live?
Kast and colleagues found that an immunity gene put into the nucleus was transcribed with no problem, generating a messenger RNA (mRNA) just the way a good gene should. But the mRNA was quickly destroyed. So, the gene was working fine but the mRNA was somehow tagged for destruction. This led to a very interesting hypothesis based on one peculiarity of the parasite’s genes: they are A/T rich. What this means is that they have an unusually high ratio of A-T base pairs compared to G-C base pairs. That bit of technical jargon isn’t by itself important. This is: lots of A’s and T’s in an mRNA molecule can trick a cell into destroying that mRNA. Why? Because the signal for “add a poly-A tail here” is made of strings of A’s and T’s. For our purposes, it hardly matters what a poly-A tail is. What matters is that this normal process (adding tails) can go haywire if someone sprinkles “add tail here” messages in places they don’t belong. That leads to mRNAs with lots of tails. And that leads to destruction.
Here’s the experiment the authors did to test their hypothesis. They surmised that the high A-T content explained the inability of cells to make the immunity protein from a gene in the nucleus. So, they made a synthetic version of the gene, one that they knew would still generate the same protein, but one with a lot fewer A-T base pairs. That version of the gene completely protected cells from the toxin. In the graph below (Figure 6B from the paper), you can see the results. Blue and green show what happens when the gene for immunity to toxin B is put into cells exposed to toxin A. It doesn’t matter whether the gene has fewer A-T base pairs (green); the antidote must match the toxin, so the cells are killed. The gene for immunity to toxin A is also ineffective at rescuing cells from toxin A (black), unless the gene has been scrubbed of excess A-T’s (red).
That’s really cool.
It’s brilliant, actually. The sneaky killer element offers the yeast cell a package deal: you can have the poison and the antidote, but you can’t have one without the other. If you have just the poison, you die. If you try to put the gene for the antidote into your genome, you discover that the gene has been wired for self-destruction if it finds itself in the wrong place (the nucleus). It’s like a device made by a Bond villain.
Stay tuned for Part II, in which we look at an extraordinary story of evolutionary conflict, in which some yeasts appear to have disarmed themselves in self-defence. Sounds weird? This is the world of selfish replicators, a world that only makes sense from the gene’s-eye view.
Image credit: Wikipedia
Kast, A., Voges, R., Schroth, M., Schaffrath, R., Klassen, R., & Meinhardt, F. (2015). Autoselection of Cytoplasmic Yeast Virus Like Elements Encoding Toxin/Antitoxin Systems Involves a Nuclear Barrier for Immunity Gene Expression PLOS Genetics, 11 (5) DOI: 10.1371/journal.pgen.1005005