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Right Side, Left Side

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!

20 comments on “Right Side, Left Side”

  1. VTJ says:

    I wonder if issues with Myosin expression could be responsible for situs inversus or other manifestations of mirror image twins. I believe those two situations are understood to arise out of a fertilized egg physically splitting late but it would be interesting to know if there is an underlying genetic contributor.

  2. Nick K says:

    My Significant Other has great difficulties distinguishing left and right, especially when she’s driving!

    1. Wes says:

      My own difficulty with that is not confined to driving. I have several relatives on my mom’s side with the same problem.

    2. Uncle Al says:

      Asperger’s syndrome (DSM !V,, useful toward functionality), autism spectrum (DSM 5, useful for selling pharma and side effects). Left-right confusion is also common among people who are bilingual in Latinate and Semitic languages. Aspies are doers beyond expectation, though there is a tendency to get lost in large (theater, stadium) bathrooms

      Put your index fingers out straight and your thumbs out perpendicular. The “L” is your left hand. One would naïvey think that would work. When you drive somewhere, draw the instructions with arrows.

  3. Sxa says:

    I recommend”Mirror, Mirror” by Pendergrast.

    Good discussion of telescopes too.

  4. Chris Phoenix says:

    I’ve reread the previous article and comments, and I still don’t see why left-right recognition requires any more explanation/mechanism than the ability to navigate spatially. If I can remember “Walk to the stream, and then the fruit tree is in _that_ direction” why can’t I remember “My right hand is in _that_ direction”?

    1. Derek Lowe says:

      I think that the whole idea of “that direction” is a recognition of three-dimensional chirality, though

      1. Chris Phoenix says:

        If our bodies were perfectly physically symmetrical, we might be initially unable to distinguish one side from the other. This is not immediately obvious, but I think you’re right.

        But the world we perceive is extremely asymmetrical. The moment we reached out with both limbs and only touched an object with one of them, we would break the symmetry. From that point (and many, many similar experiences), we’d be able to learn a difference between our limbs, and control them independently. And once we can control limbs independently, we can choose to take a step toward or away from the fruit tree.

        1. Derek Lowe says:

          The phenomenon of “hemispatial neglect” might have some bearing on this?

          1. Chris Phoenix says:

            To me, the key line is: ” space representation is more topological than symbolic.”

            I think this is consistent with what I was saying: we can (with a typical brain) learn the relative (topological) locations of asymmetric objects.

            I think we would not need a chiral/asymmetric brain to learn an asymmetric image. Do you think fine-grained asymmetry/chirality is necessary for a neural net to recognize spatially heterogeneous image features? I’d be a bit surprised, but willing to listen to an argument. But if not – I don’t think learning spatial topology needs any more brain asymmetry than learning visual topology.

            I did note that different hemispheres have different effect severity from similar lesions. Clearly the brain is asymmetrical on a large scale, and there are many other threads of evidence that confirm that. But I don’t see that as necessary to learning/recognizing topology; rather, it’s likely a result of recent specialization for language.

            This is perhaps testable: Are the brains of intelligent but non-linguistic animals (e.g. dogs, chimps, dolphins, elephants) more or less symmetric? And can dogs (etc.) learn left from right? If, as I suspect, the answers are Yes and Yes, then that weakens the argument that large-scale asymmetry is necessary to our sense of handedness.

          2. Derek Lowe says:

            To the best of my knowledge, all animals exhibit brain asymmetry, though. . .

          3. sort_of_knowledgeable says:

            Then there are the Guugu Yimithirr, with presumably asymmetric brains like the rest of us, who refer to locations in absolute terms rather that relative left or right

            https://en.wikipedia.org/wiki/Guugu_Yimithirr_people

  5. Sigivald says:

    which I believe is what allows us to consciously distinguish our right from our left and to grasp the concept of chirality at all

    That … might be a stretch? We’d presumably manage to grasp up vs. down without internal chirality, and there’s no obvious reason that left/right can’t be derived from that, especially since we’re terrestrial, not aquatic or even aerial.

    The fore/back, left/right axes aren’t obviously dependent on internal chirality, are they?

    1. Sigivald says:

      (I went and read the referenced post, which I’d long forgotten, but I don’t think it really addresses “how do we know A Left from A Right”, so much as “hey, our weirdly asymmetric brains handle left and right differently and that’s super interesting”.

      Brain asymmetry doesn’t get us up/down or fore/back, so I see that as coincidental and interesting-in-itself, not causative of left/right distinction.)

  6. Daniel Barkalow says:

    I’m not convinced that we’d actually have any trouble telling our left hand from our right hand with a symmetric brain, any more than telling our hand hand from our neck. We’ve got nerves attached to muscles that move something, and the similarity between the matching parts is less obvious than the difference. If you’ve ever learned a complicated skill with one hand (or foot) and then just tried the other side, you’ll realize that your experience is pretty much useless for that task. Furthermore, it’s actually difficult to make symmetric motions evenly, rather than that being something you need to learn to avoid doing.

  7. Anonymous says:

    Detartrated. (Had to keep it relevant to chemistry.)
    A man, a plan, a cat, a ham, a yak, a yam, a hat, a canal – Panama!
    Elapse time, relative gate to my agony. By no gay motet age, vital eremites pale.
    Straw? No, too stupid a fad; I put soot on warts. (Had to keep it relevant to Pipeline and drug discovery.)
    Evil, a myosin, is alive! (Aha! Myo disrupts the symmetry of this otherwise symmetrical statement!)

  8. Peter S. Shenkin says:

    I remember as a child having great difficulty learning left and right, and in addition I have always had a very poor sense of direction. However, post-childhood, I used to be really good at mentally visualizing chiral molecules – things like whether two 2D drawings of the same molecule with wedge and dotted bonds in different orientations are chirally opposite or similar. This is something I have had increasing difficulty doing as I’ve gotten older. I’m now 71. It is true that I don’t have to do it much, except for fun, but it seems to me that my difficulties go beyond being out of practice.

    1. enl says:

      “your right hand is the hand you write with” nearly made me fail first grade. That turned into “the left hand is the devils hand” somewhere after newyears…. I still have trouble with right and left.

      1. Anonymous says:

        In kindergarten, I was taught that “the clock is on the left side of the room.” I find that that rule still works, as long as I am facing the right — I mean, correct — direction.

  9. CB says:

    Living organisms are intrinsically non-symmetrical, because we have L-amino acids and D-sugars etc at the left and the right site. We could only be symmetric if the mirror images of the existing chiral building blocks of life would exist and occur at e.g. the left part of the organism and the known building blocks at the right part….. probably difficult to progress in evolution: the well ordened racemic organisms.
    Alternatively, building organisms with non-chiral molecules is also a nice start to create symmetric organisms: give it a try 😉

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