I have three testable hypotheses that I think can demonstrate a high degree of physics based fine tuning specific to biology that I think is comparable to what is found in cosmology. The first principle is the role of mechanical pressure in biology. Perhaps I have not done justice to the idea that I intend to convey, so I will try to remedy that situation now. First I need to explain the concept of top down causation, or better yet I will allow the physicist Paul Davies explain it, in his paper “The Algorithmic Origins of Life he wrote:
The algorithm for building an organism is therefore not only stored in a linear digital sequence (tape), but also in the current state of the entire system (e.g. epigenetic factors such as the level of gene expression, post-translational modifications of proteins, methylation patterns, chromatin architecture, nucleosome distribution, cellular phenotype and environmental context). The algorithm itself is therefore highly delocalized, distributed inextricably throughout the very physical system whose dynamics it encodes. Moreover, although the ribosome provides a rough approximation for an UC (see endnote 5), universal construction in living cells requires a host of distributed mechanisms for reproducing an entire cell.
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https://royalsocietypublishing.org/doi/10.1098/rsif.2012.0869
I think that Davies algorithmic model is an excellent description of ontogeny, and so that is the model that I am using, which is why I am also including mechanical pressures, hormones and electrical chemical signalling. However for the purpose of clarity and simplicity I am focusing just on mechanical pressures at this time. So in talking about the role of mechanical forces in ontogeny I must emphasize that I am not saying that it is always the most important factor in every single transformation the embryo/ fetus experiences, but rather that it is very often the hidden driving mechanism that is pushing the various developmental processes along.
Rather than attempt in a few paragraphs to provide a comprehensive review of this topic, using what is to me and perhaps to me alone, a logical shorthand of expressions that describe various tissue migration processes, I will simply develop the concept of how mechanical pressures can and do control the length of metaphase, and then use that example to provide a detail falsifiable hypothesis about the role of mechanical pressure in controlling metaphase has in nerve cell proliferation in the human neocortex.
To explain in the simplest way possible the reason that metaphase duration can be controlled by changes in mechanical pressure, I will use a simple analogy, please bear in mind it is only an analogy and no analogy is perfect. Imagine that you put a button on a string and tied the string to each of your pointer fingers, and then pulled your hands apart and began to spin it. You would find that the tighter that you held onto the ends the string the faster the button would be able to spin. Well this same principle also applies to the speed in DNA polymerase rotates along the DNA strand, simply reducing the amount of tension in the DNA strand, can slow down its progress prolonging prometaphase. For empirical support of this hypothesis please read the paper below:
https://www.pnas.org/content/98/15/8485
This hypothesis is further supported by a separate experiment where researchers prolonged prometaphase by applying mechanical pressure to precise points of a cell during metaphase which I post in an earlier comment, but will repost below:
https://www.pnas.org/content/109/19/7320.full
So let’s think about this quality of DNA from an engineering standpoint, by asking the following question: If you were designing a cell today why would you engineer the DNA, in such a way that the timing of prometaphase could be adjusted by slight changes in mechanical tension? I hypothesize that the answer is linked to the mechanics of tissue migration, here is how one paper describes this process:
Mechanobiology studies have shown that cell–ECM and cell–cell adhesions participate in mechanosensing to transduce mechanical cues into biochemical signals and conversely are responsible for the transmission of intracellular forces to the extracellular environment. As they migrate, cells use these adhesive structures to probe their surroundings, adapt their mechanical properties, and exert the appropriate forces required for their movements
Single and collective cell migration: the mechanics of adhesions - PMC
Now that we have this common basis for conversation, I will share with you my hypothesis about the role of mechanical pressures in the differential growth of the neocortex in humans versus chimpanzees and other mammals.
In a paper that I mentioned earlier, the authors found that a significant difference between the development of the chimpanzee neo cortex and the human one is that length of prometaphase is longer in humans than it is in chimpanzees. Now my hypothesis is that the human cells exert more mechanical force against the extracellular matrix while migrating into the neo cortex. This increased force generated during the contraction phase of its movement reduces the amount of tension in the mitotic spindle at just the right angle and just the right amount to slow down prometaphase and promote the proliferation of more neurons into the human neocortex as compared to the amount of proliferation that occurs in the chimpanzee, and all other mammals. to what happens in chimpanzees and every other.
A few days ago my hypothesis was incomplete. I needed a mechanism to increase the amount of torque in just the human cells, and I also could only look into it late at night due to other responsibilities. However after re-reading the original paper I found this sentence:
Genes with the highest specificity score encoded canonical cerebral cortex patterning transcription factors such as PAX6, ID4, and GLI3, as well as proteins involved in cell adhesion and ECM signalling (CDH4, EFNB1/2, COL4A2). Notably, no genes associated with cell cycle, kinetochore, or spindle terms were specific to human APs (Figure 8C, inset)
(Boldness added for emphasis)
Now my hypothesis made a lot more sense, but only if if the human cells had to overcome stronger adhesions to the ECM, than the chimpanzee cells that would require that they would generate more torque, just like a car has to generate higher torque when it’s stuck in the mud. This would also suggest that the human cell should move more slowly than the chimpanzee cells do which led me to discovering this paper:
It supports my hypothesis that the humans cells need to exert more torque to overcome adhesive forces and thus moves slower, by stating:
The distribution of migration speed of cells from the three species differed, with human NPCs moving significantly more slowly than either chimpanzee or bonobo NPCs (mean migration speed: human = 0.46 ± 0.19 μm /min, chimpanzee = 0.70 ± 0.31 μm /min, bonobo = 0.72 ± 0.35 μm /min, [Figure 2F (Species-specific maturation profiles of human, chimpanzee and bonobo neural cells | eLife)). By contrast, we did not find significant differences in the migration speeds between chimpanzee and bonobo NPCs.
So the hypothesis that higher mechanical forces in human nerve cells regulates the speed of prometaphase, is both consistent with the known properties of the reduced tension mitotic DNA spindle, the role of adhesive proteins in cell migration, the physics of torque, and the relative speeds between species. All it needs is direct empirical validation, something that is beyond my technical expertise, and available equipment, but well within the grasp of any scientist reading this long post, who is willing to accept the possibility that open innovation in science is still a useful proposition. Just imagine if a random inventor or the internet can use his limited knowledge on mechanics to possibly solve a long standing mystery about what makes our human neocortex unique, just imagine what you all can do. Here’s a link that I find fascinating perhaps you will too:
As I mentioned earlier it is essential to my broader hypothesis that the role of mechanical pressure in biology is understood first, before I can tie this principle to ID in post in the near future. Thanks for reading, and feedback is welcome.