Aaaaaand todaaaaay, ladies and, um, other kinds of people…. Hox genes!
Considering that I did my Honours project on them and I think they are made of awesome, I’m kind of shocked by the general lack of them here*. Hmmmmmm. Well, having just found Sambrani et al. (2013), I think today is a good time to do something about that.
Hox genes in general are “what goes where” type regulators of development. In bilaterian animals, they tend to work along the head to tail axis of the embryo. (Cnidarians like sea anemones also have them, but the situation re: main body axis and Hox genes in cnidarians is a leeeetle less clear. And heaven knows what sort of weird things happened with the rest of the animals.)
Hox genes are responsible for one of the peculiarities of the insect body plan. Unlike many other arthropods, insects have leg-free abdomens. On the left below is a poor little lobster with legs or related appendages all the way down (plus a bonus clutch of eggs). (Arnstein Rønning, Wikimedia Commons). To her right is a bland, boring insect abdomen (Hans Hillewaert, Wikimedia Commons).
As I said, Hox genes are responsible for the difference. Three of them are expressed in various segments of the abdomen of a developing insect: Ultrabithorax (Ubx), Abdominal-A and Abdominal-B. I’m going to whip out that amazing fluorescent image of Hox gene expression in a fruit fly embryo from Lemons and McGinnis (2006) because aside from being cool as hell, it also happens to be a good illustration:
(The embryo is folded back on itself, so the Abd-B-expressing tail end is right next to the Hox gene-free head)
In insects, all three can turn off the expression of the leg “master” gene distal-less (dll). However, they turn out to do so through two different mechanisms. Ubx and Abd-A proteins have long been known to team up with the distantly related Extradenticle (Exd) and Homothorax (Hth). With their partners, the Hoxes can sit on a regulatory region belonging to the dll gene and prevent its activation.
Sambrani et al. were curious whether Abd-B works in the same way. Sure enough, Abd-B also represses dll wherever it shows up. However, when it comes to interacting with Exd and Hth, differences start to emerge. For starters, those two aren’t even present in the rear end of the abdomen, where Abd-B does its business. When the researchers took the regulatory region of dll and threw various combinations of proteins at it, they found that (1) Abd-B is perfectly capable of binding the DNA on its own, (2) Exd, Hth or engrailed (another Hox cofactor) didn’t improve this ability at all, (3) Hth alone or in combination with the others actually inhibited the binding of Abd-B to the dll regulatory sequence.
Interestingly, dll repression in the anterior and posterior abdominal segments requires the exact same bits of regulatory DNA even though different proteins are involved. It looks like in the posterior segments, Abd-B actually takes over an “Exd” binding site – maybe that’s how it can do the job without getting Exd itself involved.
Furthermore, while the DNA-binding ability of Abd-B is crucial to its ability to kill dll expression, the same is not the case for Ubx. The authors speculate that cooperation with Exd and Hth kind of exempts Ubx from having to bind the regulatory sequences itself, while Abd-B, being on its own, can’t afford to slack off like that. The paper illustrates the idea with such a deliciously ugly pair of drawings that I feel compelled to post it:
(I know they’re going for colour-matching with the fluorescent images, but unfortunately glowy greens and reds that look good on a black background kind of just hurt my eyes on white.)
I don’t really have a point to make here. (There doesn’t always have to be a point, right?) There’s absolutely nothing surprising about the fact that different Hox genes evolved the same overall function in different ways - after all, they existed as separate entities long before insects lost their buttward legs. I just think Hox genes are cool, and this was an interesting look into the nuts and bolts of how they work. And that’s that.
Lemons D and McGinnis W (2006) Genomic evolution of Hox gene clusters. Science 313:1918-1922
Sambrani N et al. (2013) Distinct molecular strategies for Hox-mediated limb suppression in Drosophila: From cooperativity to dispensability/antagonism in TALE partnership. PLoS Genetics 9:e1003307.