I wrote here about chirality, on several levels, finishing up with some speculations on how we know our left hands from our right and why. As mentioned in that post, that’s one of those questions that can sound stupid and/or trivial until you start to think about it, and as the comments section proved, things tend to get out of control once you do. Chirality is a pretty profound topic, and the origins of it in living creatures has been a subject of research and debate for a long time now. There’s a new paper, though, that may have some real answers.
At some level, this has to come down to the way that all living organisms on Earth use particular chiral forms (“handedness”) of amino acids and carbohydrates. The debate on how and why that happened is most certainly not settled, but this latest work has some light to shed on the next question up: given that these biomolecules are chiral, is there one in particular, or one system of them, that is the determinant for all the others? Or does it show up in several places by different mechanisms? For Drosophila fruit flies, anyway, it appears that the answer is the first one: there is a master chiral switch, and it’s myosin.
A gene for myosin protein (Myo1D) had already been known as a situs inversus locus – if this one is deleted, fruit flies end up with all their internal organs flipped to the other side than usual. All of the fruit fly organs and anatomical systems that break left/right symmetry express myosin. In this paper, the authors show that if you ectopically express the protein in organs that don’t have such asymmetry, you force them to become asymmetric. The tissues themselves take on curved and looped forms – if, for example, you express it in the epidermis, the entire fruit fly larval form ends up with a twist, and they move by sort of a barrel roll motion rather than the usual crawling. Similarly, the wild-type fly trachea is a straight-line organ, but if you express myosin in it, it turns into a curled ribbon shape, and so on.
Mutations and deletions across the protein showed that all of its domains are necessary for this effect, as is the protein’s ATP-driven motor function. Looking at the other myosin genes, it turns out that one of them (and only that one other), Myo1C, also can induce 3-D twisting in tissues when ectopically expressed, and that one, interestingly, is of the opposite handedness to the twisting induced by Myo1D. The two can actually cancel each other out when expressed in the same tissues. That led to a series of experiments where the authors swapped domains from each protein, which showed that the direction/chirality is determined by the motor “head” domains of each. That’s the part that interacts with actin filaments, and further experiments showed that this motion seems to be the source of the chiral behavior.
So that, at least in fruit flies, is what it seems to come down to. Myosin and actin, two proteins made up of chiral amino acids, coming together in a molecular motor, the direction of whose movement is determined by their tertiary stuctures (which in turn are, of course, determined by their amino acid sequences). That’s how fruit flies end up asymmetric, and it would not surprised me if this were a conserved mechanism and responsible for how we ourselves end up asymmetric. Myosin and the myosin/actin interaction are very strongly conserved indeed; you can mix and match proteins across hugely different organisms (such as amoebae and mammals) and they will still recognize each other. And that asymmetry extends all the way to our brain structures (left and right hemispheres, at the most obvious level) which I believe is what allows us to consciously distinguish our right from our left and to grasp the concept of chirality at all. Insofar as we do!