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A ruthlessly selfish piece of DNA

A ruthlessly selfish piece of DNA

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Published by Steve Matheson
What a selfish little piece of... by Stephen F. Matheson Originally published on Quintessence of Dust, August 2011 "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" beh
What a selfish little piece of... by Stephen F. Matheson Originally published on Quintessence of Dust, August 2011 "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" beh

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Published by: Steve Matheson on Aug 02, 2011
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 What a selfish little piece of...
 by Stephen F. MathesonOriginally published onQuintessence of Dust
 
,August 2011"The Selfish Gene." "Selfish DNA." Oh, how such phrases can get people bent out of shape.Stephen Jay Gould hated such talk (seea little book called
 ), andRichard Dawkins devoted more time to answering critics of his use of the term 'selfish' thanshould have been necessary. Dawkins' thesis was pretty straightforward, and he providedreal examples of "selfish" behavior of genes in both
The Selfish Gene
and its superiorsequel,
The Extended Phenotype
. But there have always been critics whocan't abide thenotion of a gene behaving badly .Leaving aside silly bickering about the attribution of selfishness or moral competence tolittle pieces of DNA, let's consider what we might mean if we tried to imagine a really selfishpiece of DNA. I mean a completely self-centered, utterly narcissistic little piece of DNA, onethat 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 anorganismthat can fly and mate but can't eat. We can picture genes driving organisms totake 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 aboutin bloated mammalian genomes. (If you are one who prefers to think of thesetransposableelementsas beautifully-designed marvels of information transfer and storage, you can havea 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 hosthelp a gene propagate itself? We can talk about the examplesabove, and explain each through some reproductive benefit ortrade-off. But I'm not talking about negligence here; I'm talkingabout harm. Well, okay. I'm talking about
killing babies
.I'm talking about a gene that kills the embryo in which it'sexpressed, unless the embryo promises to propagate the gene.The most famous example of such an outrageously selfish geneis the Medea element, found in certain beetles. ('Medea' is bothan acronym and adeliciously evil description of the effect of the element.) Here's the basic idea: a female that carries the Medeaelement has some offspring. Some of those embryos will havethe Medea element in their genomic endowment and others won't. But all of the embryos will be exposed to the Medeaeffect, because it comes into the embryo through the egg, which was created by the Medea-
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carrying mother. The Medea effect kills any embryo that doesn't carry its own copy of theMedea 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 pieceof DNA that stoops to infanticide. Another example  was described just a few years ago in thenematode
 
,that workhorse of developmental genetics. Called the peel-zeelelement, it's just a little different from Medea: in the peel-zeel system, the embryo-killingcurse 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 thesame: only those embryos that carry their own copy of the peel-zeel element can avoidsperm-carried destruction. Now some new results, published inthis month's
 
 
,
" wasauthored by Hannah Seidel and colleagues.The group had previously shown that the paternal genetic element would kill embryos thatdidn't have an "antidote," and had explained the peculiar genetic arrangement that keepsthis element from being driven completely to fixation in the population. (An element thatkills everyone but itself would be expected to quickly infest the entire population, but thisdoesn't occur in the case of the peel-zeel element.) Although the authors knew a bit aboutthe 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 oneparticularly useful tool, especially valuable in the experimental wonderland of genetics thatis
C. elegans
: they had some mutants with perfectly good antidote function but no killingability. So they used those mutants to do some very nice genetic mapping experiments, anddiscovered 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 rightnext to the antidote, in a part of the genome that contained no known genes. Or, moreaccurately, 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 ina gigantic DNA sequence.) And Seidel et al. had just discovered a new gene – the peel-1gene. 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 arethe only cells that express it. The delivery vehicles ensure that each embryo is provided withan adequate dose of the toxin. Oddly, the lethal protein actssomewhat late in development, in skin and muscle cells, andthe embryo dies a grisly death unless it carries the antidote. Theimage on the right (from the cover of theJuly 2011 issue of 
) shows two affected embryos (the blobs on theleft and right) and one happily normal worm.
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