I was going to make this discussion a two-part post, but after writing a bit of this post, I think I’ll divide it into three, as it would be too long. The last bit, on artificial selection for directional asymmetry, will be tomorrow.
In my first post on this issue yesterday, I discussed the problem of evolved directional asymmetry (a trait is always different on the right than on the left, and in the same direction) as opposed to antisymmetry, in which the trait varies between the right and left sides among individuals, but randomly. An example of directional asymmetry is the male narwhal’s tusk, which is an enlarged left canine tooth, so the “tusk” (the enlarged tooth) is always on the left side of the midline. An example of antisymmetry is the large claws of male fiddler crabs, which are random with respect to body size: half of male crabs have big right claws, and the other half big left claws.
Here’s one example of directional asymmetry in a species, the twospot flounder, which always develops to flatten on its right side (flounders begin developing vertically, like normal fish, but then flatten out, with the eyes migrating over the top of the head so both are on one side). Other species of flounders lie on their left sides, and some lie randomly on either side (anti-symmetry). Crossing experiments between species suggest that the directional asymmetry has some genetic basis.
My question yesterday was this: to get directional asymmetry, there must be a genetic program that recognizes right versus left so that a trait’s formation can be genetically activated on only one side of the body. But that presupposes some cue, perhaps a molecule in the internal environment, that can activate and/or repress genes on one side only. Such cues seem unlikely in a bilaterally symmetrical organism, for the chemical “gradients” from the midline to the right or left margins should be the same for equivalent points (as opposed to the top/bottom or front/back gradient). So how, in an ancestor that is perfectly symmetrical bilaterally, can a directional asymmetry evolve? What cues could those genes use to know where they are?
Now of course once a single directional asymmetry has evolved, then there’s already a left-right difference, and further directional asymmetries can evolve cueing off of that first one. And that could, in turn, produce any number of directional asymmetries. But the question remains: how does the first directional left-right asymmetry evolve in a bilaterally symmetrical organism?
In the past eight years, scientists have been coming up with answers, and the issue is discussed in a nice piece at Quanta magazine by Tim Vernimmen. There are two possibilities.
- In 2009, Nobutaka Hirokawa et al. reported that the “node” in vertebrate embryos—a pit in the bottom midline of the early embryo—is surrounded by cilia that beat in a rotational motion in one direction only, causing a flow of embryonic fluid toward the left. As the authors say:
Through studies of the flow of materials within cells, we serendipitously found that nodal cilia are actually motile and vigorously rotating. This rotation generates the leftward flow of extraembryonic fluid in the nodal pit. The directionality of this flow, termed nodal flow, determines laterality. Thus, quite unexpectedly, a physical process, fluid flow, was identified as the initial L/R symmetry-breaking event. In this review, we first summarize the discovery of nodal flow and then discuss how this leftward linear flow is generated in a fluid dynamic manner by the rotational movement of cilia.
You can see the directional beating of the cilia and the leftward flow of fluid in the movies embedded in Hiokawa et al.’s paper—particularly movies 3 and 4. Have a look!
What the authors found, then, was that a directional motion of the cilia produced directional asymmetries in the embryo, so that the flow itself can differentially activate genes on the right versus left sides. But why do the cilia beat in only one direction? Well, if they all beat in different directions, there would be no fluid movement, and which direction they all “decided” to beat initially in may have been a random result of an ancestral gene. But once that’s determined, then it sets up a consistent left-right asymmetry. This may be the cue for directional asymmetry in many vertebrates. Support for this comes from the observation that mutations that damage cilia or their movement in vertebrates species cause screw-ups in the antisymmetry.
- Some organisms, though, don’t have these nodes with cilia. The Quanta article implicates another instigator of handedness in such species: the presence of the protein myosin (a “motor protein”) that appears to act asymmetrically in organisms like fruit flies and worms, making cell division asymmetrical and producing handedness. How this happens isn’t specified in the original paper nor in the Quanta article, but we know that screwing with myosin through mutations screws up handedness. Perhaps something about the asymmetry of the molecule itself induces a directionality in its action.
The figure below shows directional asymmetry in two organisms lacking ciliated nodes, the fruit fly Drosophila and the worm Caenorhabditis, as well as an organism with nodes—H. sapiens. The figure is taken from a 2011 paper by Christian Pohl:
Now there are other possible mechanisms for generating handedness as well, and I suspect that the two listed above don’t exhaust all the possibilities. Amino acids themselves have handedness, as all organisms use the L- configuration rather than the mirror image R- configuration. The figure below shows the mirror-image symmetry of a single amino acid, with has two “enantiomers”, left and right. All organisms use only the L-isomer, and the adoption of that versus R- forms may have just been an initial accident, like the directional beating of the cilia. There’s no reason why we couldn’t have proteins composed of only R- amino acids, but we couldn’t have them with both L and R forms, as proteins couldn’t form properly if they used both types—just like you couldn’t have a group of cilia beating in all different directions.
This gives an inherent asymmetry to amino acids, and thus to the proteins they form. And proteins themselves, once synthesized, may also fold up asymmetrically, giving another way for a bilaterally symmetric organism to have a cue for handedness.
Still, to a large extent the evolutionary and developmental basis of directional asymmetry remains mysterious, largely because the molecular underpinnings of development are mysterious and hard to study.
One question that occupied me when I was younger was this: if you take an organism that is, by and large, bilaterally symmetrical, like Drosophila (though there is a bit of handedness in a couple of its traits), could you impose artificial selection on it to produce handedness? That is, could you select for a line of flies whose right eyes were bigger than their left, or who had more bristles on their left side than on their right (and vice versa in both cases)? How hard would that be? Given the absence of marked bilateral asymmetries in species like Drosophila that could act as developmental cues for the successful selection of directional asymmetry, you might think it would be hard—even though virtually every other trait in Drosophila can be successfully changed by artificial selection. Tomorrow we’ll learn the answer to my question.