High school levels of science tend to leave us thinking that everything in our bodies is the result of a bunch of chemical reactions, but academic levels of science has a slightly more elaborated view on this.
Let’s say that I were to explain to you what happens inside a brain, how much of my explanation would have to do with the actual formation and breaking of chemical bonds? And how much of it would be more on the level of ionic movements, and interactions not between atoms, but interactions between groups of atoms?
Sure, if I were to talk about the actual cellular metabolism of the neurons I would have to talk about chemical reactions, but just talking about how the molecules, the proteins, the ions, the neurotransmitters, work together in general… There is no actual chemical reaction going on. When two protein dimers combine into a tetramer, they’re not changing into another substance. The type of bonding is not comparable; it is much weaker than an actual covalent bond.
You may not think much of the difference between the two, but there is one difference, and this one difference is the one that will make all the differences between the haves and have nots of life.
There are two molecular forces. One is an intramolecular force, a short-distance force between a few atoms, and the other is an intermolecular force, a weaker long-distance force between many atoms. Both have great effects on our lives, but one will stand out more than the other when it will come down to describing what is happening inside our bodies. To use a bad pun, chemical reactions explain the why, and intermolecular forces explain the how. DNA clumps together into a double helix. How? Intermolecular forces in the form of hydrogen bonds. Why? Because somewhere down some complicated chemical pathway, a whole armada of enzymes add up a few hydrogen atoms here, and a few nitrogen and oxygen atoms there, and then links up all these blocks together into a long chain of polymers, such that the aforementioned hydrogen bonds can occur and create the double-helical structure.
Most of the time it is not the chemical reactions themselves that move our bodies, rather these chemical reactions provide the context in which intermolecular forces will become capable of moving our bodies. We could go so far as to say that the effects of one chemical reaction can lead to whole cycles of intermolecular interactions. Intermolecular forces are more dynamics, more varied, more complex, more mysterious.
Going back to the example of the brain, the interplay of neurons does imply many chemical reactions, mostly involving phosphate in one way or another, but once phosphate has played its role, once the system has the energy it needs, just for a moment, for that one moment it’s not just the chemical reactions that are the driving force anymore.
We have molecular movements, moving from the most concentrated section into the least concentrated section, all molecules must move down their gradient of concentration in and out the cell, and in and out of its many compartments. Here we have ions, electrically charged particles moving across the cellular membrane, causing protein channels to shift shape and open up their porous gates allowing in more ions.
Everywhere we have proteins twisting around and colliding into other proteins, causing them to twist around and change shape as well. Chemical energy fuels the formation and dissociation of the proteins forming the microtubules, fuels the transport of vesicles across the microtubules via motor proteins, but it is the movement of the molecules that move our bodies, not the chemical reactions themselves. The chemical reactions only provide the energy to form the bonds that will become the center of these movements. When you move, all these other molecules are folding along with you via these other molecular forces.
We are not just the result of a bunch of chemical reactions, we are the after effect of a bunch of chemical reactions.
And now, think that if you were to line up all your chemical reactions in the right order, then it would become possible to form chains of whole molecules, with a very specific sequence, which should lead to a very specific type of after effect, or at very least a very specific range of after effects. It’s that second part that’s interesting. What makes the difference between one after effect and another? This is interesting because changing how the chemical reactions occur can be complicated and messy, there’s all these regulations already in place, but changing how a molecule fold, it seems easier, it seems more malleable, more controllable.
All you need to do to change how a molecule fold is to add up the right drug, at the right place, at the right time. If you’re a drug manufacturer, what you usually want is for your drug to non-covalently bind to some hormonal receptor, or some enzyme, but you don’t necessarily want your drug to actually chemically react inside the body. Drugs can be hard on the liver for that very reason, the body has not evolved to deal with the kind of side products that can be created when the drug is catabolized and broken down into smaller pieces.
But back to the relation between intramolecular and intermolecular forces. A sequence of molecules, that’s easy to understand. You could easily wrap that around any good brain, but how are multiple sequences of molecules going to work together?
If you were to analyze the structure of a protein using X-ray crystallography, the first thing you would notice is that the protein is not just a string of molecules, but a string of molecules that spontaneously fold unto itself. You would be able to actually see the effect of the various intermolecular forces.
(Looking at the structure of many proteins, or any other type of polymers for that matter, it would seem logical to conclude that only parts of a sequence, not the whole sequence, would be capable of interacting with other molecules at any given time.)
Let’s say I have a string of protein, and some of the molecules for whatever the reason don’t like water so they end up clustered together at the core, then the other proteins will only be able to interact with the molecules on the surface.
Only the molecules on the surface actually contribute to the function of the protein within the organism. The rest contribute to the structure yes, but their conservation is much less vital to the good working of the protein, because the non-covalent bonding actually happens on the surface.
We have proteins that act as transporters, markers, catalysts, storage units, structural units, and so on, for each function the key molecule that will make the non-covalent bonding with this ‘other molecule’ will be the molecules on the surface. The core can only interact with itself. Maybe we could use the term ‘apparent sequence’ to define the part of a sequence that is visible to other molecules.
So the initial unit of the polymer, the native sequence, can have some control over what the first apparent sequence is going to be, and this first apparent sequence will also depend on the initial environment the protein is exposed to. For example, if I were to produce a protein inside the more negatively charged cytoplasm, or inside the more positively charged endoplasmic reticulum, or if I were to produce a protein from A to Z with either the Z side or the A side coming out first, I might get the same protein in all scenarios, but each time with a slightly different level of functionality for a given task.
And if the environment of the cell were to randomly change, then each differently folded protein would be able to respond in a slightly different way, as to help the cell maintain its stability… or not, it could make it worst. Proteins often do get misfolded. Point is, evolution will care more about preserving the molecules on the surface of a protein than those on the inside, as long as the intermolecular forces at the core remain strong enough not to disturb the good functioning of the protein.
I remember in my first molecular biology class, the professor would tell us that when two species had the evolution of a certain protein converge together, you could tell from the sequence alone that the protein came from two different lineages of species, because the two would have similar surface molecules on their protein sequence, but the molecules at the core would be dependent only on the lineage not the function.
You could have two separate lineages converge into one, meaning not that they would become one, but meaning that these two different species would evolve out of different ancestors to eventually look and behave alike.
Now here’s the tricky part, the native sequence of a molecule can influence the apparent sequence, but the apparent sequence can also influence the native sequence. For example, if I have a protein that performs a certain function benefiting the organism, but this protein A also bind to a protein B, clumping together changing the shape of A and muting A’s function, then protein A cannot benefit the organism anymore. When both A and B are expressed together, the gene coding for protein A becomes at risk from being weeded out, or of becoming permanently silenced in the form of junk DNA.
But what if… what if we could invent some drug that would non-covalently bind to protein B, preventing B from interfering with A. Then A becomes useful again. We are increasing the chances of the gene encoding protein A to spread within the genetic pool, and to be co-expressed along with protein B.
Over a long period of time, a constant nurture can change a pervasive nature. We can control evolution by controlling the environment, we can influence the genetic destiny of future generations. What you have to get from all that is that you don’t have to change the DNA sequence to change how the DNA works. The sequence is capable of changing and correcting itself in the long run. In the meantime, what we need to do is to help our genetic heritage manage itself more properly.
In conclusion, by alternating the environment and the apparent sequence of molecules, you can change not only the apparent sequences of other molecules, with enough time and with a little help from natural selection, you can change the native sequence as well. What it all really ought to show us is just how much the nurture vs nature dichotomy is at the heart of 21st century genetics. Good genetics is not about purity, is not about diversity, it’s about balance — it’s about finding that perfect evolutionary stable ratio, and if my personal experiences have taught me anything, that balanced ratio will not be 50/50. The world is not so simple in that way; equality everywhere is not a fair thing. It’s not balanced.
So does the equation need more chicken, or more egg? And maybe it’s really not about what came first but really which one of these two states is the most stable. We all have our suspicion as to the answer to that, but this is one answer that will have to wait for another day.