“The Selfish Gene.” “Selfish DNA.” Oh, how such phrases can get people bent out of shape. Stephen Jay Gould hated such talk (see a little book called The Panda’s Thumb), and Richard Dawkins devoted more time to answering critics of his use of the term ‘selfish’ than should have been necessary. Dawkins’ thesis was pretty straightforward, and he provided real examples of “selfish” behavior of genes in both The Selfish Gene and its superior sequel, The Extended Phenotype. But there have always been critics who can’t abide the notion of a gene behaving badly.
Leaving aside silly bickering about the attribution of selfishness or moral competence to little pieces of DNA, let’s consider what we might mean if we tried to imagine a really selfish piece of DNA. I mean a completely self-centered, utterly narcissistic little piece of DNA, one that not only seeks its own interest but does so with rampant disregard for other pieces of DNA and even for the organism in which it travels. Can we imagine, for example, a piece of DNA that deliberately harms its host in order to propagate itself?
Sure, we might picture genes acting in naked self-interest, perhaps colluding to create an organism that can fly and mate but can’t eat. We can picture genes driving organisms to take outrageous risks in order to reproduce. And we can picture millions and millions of “jumping genes” that don’t seem to care at all about the host’s welfare while they hop about in bloated mammalian genomes. (If you are one who prefers to think of these transposable elements as beautifully-designed marvels of information transfer and storage, you can have a pass on that last one for now, because you won’t like where we’re going with this.) But can we picture a gene that actively harms its host in order to get ahead?
At first, this might seem ridiculous. How can harming the host help a gene propagate itself? We can talk about the examples above, and explain each through some reproductive benefit or trade-off. But I’m not talking about negligence here; I’m talking about harm. Well, okay. I’m talking about killing babies.
I’m talking about a gene that kills the embryo in which it’s expressed, unless the embryo promises to propagate the gene. The most famous example of such an outrageously selfish gene is the Medea element, found in certain beetles. (‘Medea’ is both an acronym and a deliciously evil description of the effect of the element.) Here’s the basic idea: a female that carries the Medea element has some offspring. Some of those embryos will have the Medea element in their genomic endowment and others won’t. But all of the embryos will be exposed to the Medea effect, because it comes into the embryo through the egg, which was created by the Medea-carrying mother. The Medea effect kills any embryo that doesn’t carry its own copy of the Medea element. The survivors are the ones that carry the element. Pretty smart, huh?
How this works, exactly, is not well understood. But Medea isn’t the only selfish little piece of DNA that stoops to infanticide. Another example was described just a few years ago in the nematode C. elegans, that workhorse of developmental genetics. Called the peel-zeel element, it’s just a little different from Medea: in the peel-zeel system, the embryo-killing curse comes from the dad. (Selfish elements like this are quite rare, and this paternally-acting system is the only known element of that kind.) But the sick story is otherwise the same: only those embryos that carry their own copy of the peel-zeel element can avoid sperm-carried destruction. Now some new results, published in this month’s PLoS Biology, are revealing how this evil plan is carried out. The article, “A Novel Sperm-Delivered Toxin Causes Late-Stage Embryo Lethality and Transmission Ratio Distortion in C. elegans,” was authored by Hannah Seidel and colleagues.
The group had previously shown that the paternal genetic element would kill embryos that didn’t have an “antidote,” and had explained the peculiar genetic arrangement that keeps this element from being driven completely to fixation in the population. (An element that kills everyone but itself would be expected to quickly infest the entire population, but this doesn’t occur in the case of the peel-zeel element.) Although the authors knew a bit about the antidote gene (called zeel-1), they knew nothing about the killer gene or how it worked; they knew only that it was probably very close to the antidote gene. They did have one particularly useful tool, especially valuable in the experimental wonderland of genetics that is C. elegans: they had some mutants with perfectly good antidote function but no killing ability. So they used those mutants to do some very nice genetic mapping experiments, and discovered the precise locations of the mutations that abolished the lethal effect. Interestingly, those mutations were in an “intergenic interval” in the fully-sequenced C. elegans genome, right next to zeel-1. In other words, the killing activity seemed to be right next to the antidote, in a part of the genome that contained no known genes. Or, more accurately, it contained no annotated genes. It turns out that we’re still discovering new genes in fully-sequenced genomes. (It’s actually not that easy to identify a bona fide gene in a gigantic DNA sequence.) And Seidel et al. had just discovered a new gene - the peel-1 gene. It makes a protein somewhat similar to zeel-1.
Once they had the actual gene in hand, the authors could probe the protein’s function. They showed that it is packed into a particular type of delivery vehicle inside sperm, which are the only cells that express it. The delivery vehicles ensure that each embryo is provided with an adequate dose of the toxin. Oddly, the lethal protein acts somewhat late in development, in skin and muscle cells, and the embryo dies a grisly death unless it carries the antidote. The image on the right (from the cover of the July 2011 issue of PLoS Biology) shows two affected embryos (the blobs on the left and right) and one happily normal worm.
In another cool experiment, the authors turned on the death gene artificially in adult animals, and it killed them just fine. They could save those otherwise-doomed worms by turning on the antidote artificially.
The peel-zeel element, then, is a great example of a truly ruthless selfish genetic element. The toxin and the antidote are side-by-side in the genome, so that an animal with the antidote will almost certainly also receive the toxin. (Think about how different things would look if the antidote gene were separate from the toxin; the toxin could quickly lose its ability to propagate itself through the generations.) And the toxin is sperm-delivered to all embryos. This combination of traits allows the paternally-carried element to kill any embryo without a copy of the element.
As far as we know, the peel-zeel system serves only its own interests. It offers no fitness advantage to its host, and is likely instead to exact a cost. Its presence in the nematode genome is easy to explain in a biosphere teeming with “selfish” DNA that admits no evident “purpose” beyond its own propagation. That’s not to say it can’t be useful; as an accompanying commentary notes, DNA-encoded toxin/antidote systems could be employed by well-meaning humans to seemingly benevolent ends. But whether or not one chooses to see the peel-zeel system as a product of “design,” the pattern of “selfish” propagation is hard to miss. And, surely, hard to restrain.
[Cross-posted at Quintessence of Dust.]
Seidel, H., Ailion, M., Li, J., van Oudenaarden, A., Rockman, M., & Kruglyak, L. (2011). A Novel Sperm-Delivered Toxin Causes Late-Stage Embryo Lethality and Transmission Ratio Distortion in C. elegans. PLoS Biology, 9 (7) DOI: 10.1371/journal.pbio.1001115