Bone Growth Demonstrates Irreducible Complexity and Hierarchical Control
David Coppedge
Picture a linear bone growing. Say it’s a leg bone, with attachment points for muscles and tendons along its length. Picture one such protrusion located a third of the way from one end. If the bone grows only at one end, the protuberance will migrate from its 1/3 position, causing problems for the tissues that need to attach there. If the bone grows at both ends, the same problem can occur.
How does the bone “know” to keep its structures at proper ratios along its length as it grows? That problem was investigated by a team of Israeli scientists publishing in PLOS Biology.
Although bidirectional elongation is a universal mechanism for bone growth, it nevertheless introduces a major challenge to bone morphogenesis. A fundamental characteristic of the unique morphology of each long bone is a set of protrusions of varying shapes and sizes, which are scattered along the exterior of the bone and thus break its morphological symmetry. These superstructures, known as bone ridges, tuberosities, condyles, etc., are necessary for the attachment of tendons and ligament as well as for articulation. To perform these functions they are located at specific positions along the bone. Bone superstructures emerge during early skeletogenesis. During growth, bones elongate extensively by advancement of the two growth plates away from the superstructures. It is therefore expected that during elongation, superstructures would remain at their original position near the center of the bone. Nevertheless, the end result is proper spreading of superstructures along the mature bone, which clearly implies the existence of a morphogenetic mechanism that corrects their locations.
Surprised by the Implications
Bones end up with the right ratios, in other words, but how do they get that way? The team wanted to know if bone growth is isometric (“same-measure”) or allometric (“other-measure”). If isometric, the bone’s ratios should be maintained during growth. If allometric, the ratios should converge on the proper position at the end of growth. They were surprised at the result and the implications:
Strikingly, analysis revealed that the relative position of all superstructures along the bone is highly preserved during more than a 5-fold increase in length, indicating isometric scaling. It has been suggested that during development, bone superstructures are continuously reconstructed and relocated along the shaft, a process known as drift. Surprisingly, our results showed that most superstructures did not drift at all. Instead, we identified a novel mechanism for bone scaling, whereby each bone exhibits a specific and unique balance between proximal and distal growth rates, which accurately maintains the relative position of its superstructures. Moreover, we show mathematically that this mechanism minimizes the cumulative drift of all superstructures, thereby optimizing the scaling process. Our study reveals a general mechanism for the scaling of developing bones. More broadly, these findings suggest an evolutionary mechanism that facilitates variability in bone morphology by controlling the activity of individual epiphyseal plates.
It’s strange to see “evolutionary” and “mechanism” juxtaposed, since the former means blind and unguided, but the latter means organized for a purpose. Indeed, there is a purposeful function going on in bone growth: to keep the bone’s ratios to its superstructures constant. The mechanism required to achieve it implies that both of the growth plates have to “talk” to each other and continually adjust their growth rates so that the structures do not drift.
But That’s Not Enough
The structures have to drift a little, because otherwise they would grow closer to the center as the ends elongate. Drift is achieved by a structure dissolving bone on the inner side and re-growing it on the outer side. In this way, the ratios between them are maintained from earliest embryonic stages through adulthood.
The level of control required to achieve isometric growth implies irreducible complexity and hierarchical control. Apparently the controls are different in different parts of the body. They point, for instance, to earlier findings that “forelimb bones tend to grow away from the elbow joint, whereas bones in hind limbs tend to grow toward the knee joint.” Even though they are evolutionists, they admit there’s no evidence this mechanism evolved.
These findings and ours clearly imply the existence of additional mechanisms that control the specific activity of each growth plate. Interestingly, some of these works were performed on other model animals such as rat, pig, rabbit, chick, and humans, suggesting that asymmetric growth of long bones is evolutionarily conserved across species.
Can their concluding summary be incorporated into a neo-Darwinian mechanism involving blind process of mutation and selection? Put yourselves in their shoes and try to imagine a way to Darwinize the findings:
In this work, we uncover the isometric nature of longitudinal scaling of long bones during growth. Using a newly developed algorithm, we recover for the first time, to our knowledge, the morphogenetic sequence of developing long bones from early embryonic stages to maturity. These data enabled us to provide accurate assessments of both the specific activity of the different growth plates and the drifting patterns of symmetry-breaking elements along the bone shaft. Based on these analyses, we conclude that longitudinal growth patterns in each bone are adjusted to preserve isometry. The constant tendency of the growth balance to protect element positionsstrongly suggest that symmetry-breaking elements are involved in the mechanism that regulates the differential activity of growth plates.
There’s design hidden in their passive verbs; “patterns … are adjusted“; “symmetry-breaking elements are involved in the mechanism that regulates” the activity. But how could a mutation to the growth plate at one end of a bone affect the regulation of a growth plate at the other end? How could a mutation that causes symmetry-breaking in the drift of one structure affect the coordinated outcome of the other structures? And how could mere chance orchestrate all the dynamic elements at play in the growth of a bone and its superstructures to end up with a functional adult bone, with all its muscles, tendons, and ligaments attached at the right places, so that the leg or arm actually works? When Haeckel drew those embryos, he had no idea what he was oversimplifying!
No Bones About It
In a companion article in PLOS Biology, (“Make No Bones About It: Long Bones Scale Isometrically”), science writer Caitlin Sedwick mentions another interesting finding:
Unexpectedly, the authors’ analysis showed that, while a few elements do drift, the rest do not. In fact, the researchers found that for each bone, a transverse plane can be drawn at the location where the ratio of the plane’s distance to either end equals the ratio of growth rates at the respective ends (Fig 1, top panel). This “fixed plane” always falls nearby the non-drifting elements, and only the elements that are significantly distantfrom this plane show evidence of drift. However, the location of the fixed plane, and therefore an element’s relationship to it — which predicts the amount of drift needed to maintain the element’s relative position on the bone — will shift during development if the ratio of growth rates at the ends change.
The “fixed plane” is, therefore, another element that must also be under regulatory control. The two growth plates and the fixed plane are regulated together to minimize drift and optimize the energy needed to maintain isometric scaling.
What seems obvious here is an overarching design plan that operates with top-level control. The process needs to foresee a desired end point, and coordinate all the activities at multiple levels, from the body plan down to the cellular machines, to achieve it. Such mechanisms can be programmed to work autonomously, but are inaccessible to natural processes lacking foresight.
No comments:
Post a Comment