If you actually read it, this isn’t a physiological response, just different mutations from those that caused the original phenotype. All it tells you is that there are many possible genomes that would produce similar phenotypes, and a reversal of selection acts on whatever mutations present themselves, not just on direct reversals of the original mutations.
It would really help if you would explain what point you’re trying to make about evolution.
Sure, if you’re looking to produce a certain result in a month or a year, you’ll need to invest engineering effort and expertise to regulate the forces.
Now suppose you have a billion and a half years at your disposal. Does that change the need for careful, up-front human engineering?
Best,
Chris
I think it would Chris, since you’re a data scientist I’m sure that you are familiar with the phenomenon of stochastic resonance.
This is my conceptual model of the relationship between physiology and evolutionary mechanisms. I think that the near neutral mutations that evolutionary biologists study so intently are the equivalent to the white noise that organisms use to resolve the almost infinite number of possible phenotypes, into a much narrower predetermined range of phenotypes that can actually exist within interfertile populations. This made me wonder if sequence similarity might also have a biomechanical explanation, but to my disappointment this idea seems difficult to resolve currently due to the limits of nanotechnology as you can read about here:
So where did the signal come from? From my standpoint the hypothesis that bottom up evolution uncovered just by chance how to use mechanical feedback loops to create a variety of top dow bio-mechanical systems, is sort of like expecting white noise to begin producing intelligible speech due to a stochastic process running for billions of years despite there being no preexisting signal. So from my standpoint the ID movement should be obsessed with biophysics and physiological constraints of evolution, as opposed to conjecture about genetics. I think that would transform the movement into a pro-science research based enterprise which I think would benefit everyone.
What that analogy lacks is a mechanism by which particular patterns of sound will become more stable and therefore subject to ongoing modification and increase in complexity over time.
In evolution this stability is accomplished thru self-replication, so that even if a specific molecule is not stable over prolonged periods of time, a particular type or arrangement of molecule will be so stable.
I do not see where in your analogy this crucial aspect of evolution is accommodated.
This seems to be a question concerning the origin of life, not about the workability of the evolutionary process. Once you’ve got the non-perfect propagation of heritable information through generations, you’ve got evolution and natural selection, and thus the capacity to sample the fitness-effects of phenotypes among all the noise variation that keeps being generated by mutation and recombination. From a biophysical perspective evolution appears fundamentally unavoidable once you’ve got reproduction and inheritance.
Of course, the origin of life is still largely an unknown, and there are many candidate explanations for the origin of self-propagating heritability, most of which have yet to be experimentally tested.
My thinking on this came about because I thought deeply about what is the difference between a physiologically derived change in gene expression and a evolutionary one. If I thought about what the best examples of genetic evolution have in common the one thing that came to mind is that they have much more relaxed physiological constraints than a more complex organism like a plant or animal.
A virus is a simple selfish gene that adapts to whatever it’s current host’s physiology is. Cancer have escaped the physiological constraints of whatever tissue it originated in and bacteria can always borrow genes from its neighbors in a pinch so none of the above examples are really physiologically appropriate examples of what the contraints of evolution in complex organisms might be.
If you look at plant and animal development however every cell type in our bodies for example are the result of physiological pressures such as mechanical forces, galvano taxis, chemical gradients and hormones controlling gene expression from the top down. Since the changes in gene expression are under physiological control during development the real question is how lose are those controls, I think that only a detailed understanding of how those controls are? From the few developmental biologists I spoke to this seems to be an open question. My thinking is that those who are skeptical of evolution are in a good position to strengthen their case by studying these constraints objectively. Regular Evo Devo biologists who think there is an evolutionary path seem to be confused as to how exactly it works, here’s what one paper says:
The third and last deadlock concerns our difficulty in connecting (macro-)evolutionary comparisons of developmental processes to evolutionary dynamics at the population and species level. In this case, the main challenge is to find suitable model systems that allow us to combine detailed studies of the mechanisms of development with accessible and informative measures of phenotypic trait variation between closely related species or, even better, between individuals within particular populations. One of the main questions in this area is whether developmental processes evolve through mutations of small effect, affecting many loci, or whether mutations of central regulator genes with more drastic consequences play any role at all (see, for example, Akam 1998; Orr 2005; Stern 2010). There is much promising progress in this field (recently reviewed in Nunes et al. 2013). However, we only understand very few developmental processes in a small number of model organisms in a detailed mechanistic way. For this reason, most population-oriented EvoDevo studies still rely on statistical-correlative rather than on causal models of genetic architecture.
Maybe it’s time for a fresh perspective, it was only when I began thinking about how important the concept of junk DNA is to modern evolutionary theory that I realized that a detailed understanding of the importance of the how molecular pressures regulate gene expression starting from the tissue level down to the kineticore and histones can change that narrative in the favor of ID. Because if selection is a metaphor for physiological constraints, the use of viruses and cancer to demonstrate the inevitablity of evolution occuring as described by evolutionary theory will go away.
I find it very difficult to understand what you’re saying here, possibly because you’re using many terms differently from the meanings I’m used to, possibly because you use citations and quotes to mean something different from what the authors meant, possibly both, and possibly other things too. Could you please try to articulate your message clearly, just to start with? Then we might discuss its merits and any evidence for or against it.
True to some extent, but those physiological pressures are themselves responding to genetics. Most importantly, the differences between species are fundamentally genetic, since genomes are the means of inheritance. If we want to understand evolution, we must realize that it results from genetic changes. Other changes in development are secondary effects.
This is an interesting idea. However, where is the evidence that physiology is inherently bistable?
Are you referring to the signal of evolution?
What is the scientific evidence that biomechanical systems are top-down? This assertion seems like a conjecture that a computer scientist unfamiliar with biology might make. Then again, I’m not a biologist so I’m not 100% sure.
There are certainly stochastic forces identified by the theory of evolution, but I doubt a biologist would characterize any of them as white noise. Again, that seems like a conjecture a computer scientist unfamiliar with biology might make.
Genetic sequences map to amino acid sequences which map (in complex ways) to phenotypes in biological systems. Some of those phenotypes are more favorable to successful reproduction than others, of course.
If it is reasonable to compare this biological mapping to a computational neural network, the weights of the input layer would correspond to the DNA and the intermediate systems (between the DNA and the phenotype) would be largely fixed weight layers. So natural selection would be like a loss function on phenotypes that modifies genetic sequences similarly to the way that gradient descent uses backpropagation to modify the input weights in a neural network.
My apologies to those who have not had the pleasure or pain of building computational neural networks.
This is a laudable goal. I’m not sure that biophysics and constraint analysis is the path to success–but of course, I’m not a biologist, so don’t let me discourage you from exploring the path.
The advice I am sure of is that you would need to gain a much greater command of the state of the art in biology to be able to exercise the influence you aspire to.
Best,
Chris
I would describe embryonic development as being under genetic control, not physiological control. What physiological stresses does a 100 cell embryo experience that would start the bilaterian body plan?
They are tight enough that humans still give birth to recognizably human offspring. It’s not as if humans exposed to different stressors suddenly causes them to give birth to something more like other apes or more distantly related primates.
As @John_Harshman seems to allude to, our physiological responses to the environment are ultimately an expression of our genetics.
That paper is discussing mutations which are heritable genetic changes. I think we would all agree that the fine details of embryonic development and Evo-Devo are hard to suss out, but everyone in the field seems to agree that the genetic differences between species are responsible for the phenotypic differences.
The first thing you would need to tackle is why there is no sequence conservation in junk DNA.
I have 35 years of experience in studying genetics, biochemistry, and cell biology, and that sentence makes absolutely no sense to me. Would you please elaborate?
If one is talking about science, the only thing with the potential to “change that narrative in the favor of ID” would be to advance and rigorously test ID hypotheses.
Do you have a hypothesis?
I wrote a comment, which was not posted, saying that @Geremy’s lengthy account sounded like BS to my non-expert ears. It is reassuring to have the experts confirm that my ears were right.
To many lurkers, his posts might seem smart and well-reasoned due to all the sciencey words littered in them. To those who are informed or possess expertise in relevant areas, it appears mostly like gibberish.
I have 35 years of experience in studying genetics, biochemistry, and cell biology, and that sentence makes absolutely no sense to me. Would you please elaborate?
To answer your point here I would like to direct your attention to 3 papers. The first paper talks directly about the mechanics of gene expression, so if you read it you might understand my point a little better. It is linked below:
The second paper demonstrates a simple causal relationship between mechanical pressure and metaphase progression. Researchers artificially controlled it by carefully calibrating the direction of mechanical pressure applied to a cell using cantilevers. It is linked below:
https://www.pnas.org/content/109/19/7320.full
In the third paper researchers are trying to determine the origins of the neocortex. Their research led them to the duration of metaphase. They write:
The prometaphase-metaphase lengthening in humans occurs upon neural differentiation
To investigate the origin of the longer metaphase in human than chimpanzee APs, we measured mitotic phase lengths in the original iPSCs used to grow the cerebral organoids. This revealed that both the human and chimpanzee organoid APs had a longer prometaphase-metaphase than their respective iPSCs of origin, showing that this general lengthening was due to the transition between iPSCs and the organoids of both species (Figure 6A,B,E). In human APs, however, the lengthening was greater than in chimpanzee APs.
The researchers confused by the fact that what they call spindle orientation dynamics are similar in human and chimpanzee because they are aware of the fact that spindle position is correlated to the duration of metaphase. My admittedly speculative hypothesis for this particular situation is that the orientation is not the determining factor but rather the direction of mechnical pressure as demonstrated by the second paper.
In any event what I am saying is that mechanical pressures and other physiological inputs are what direct the development of the embryo and fetus, and that changes in gene expression which are seen by evolutionary biologists as causal are instead merely often associated with a particular physiological state. I would expect the direction of causation to go both ways, but to be dominated by physiological constraints.
If one is talking about science, the only thing with the potential to “change that narrative in the favor of ID” would be to advance and rigorously test ID hypotheses.
Do you have a hypothesis?
Yes I actually do but first I want to establish both the limited explanatory power of genetics, and the superior explanatory power of mechanical pressures in determining inherited phenotypes.
To answer your first point, in humans and many other vertebrates 100 cell embryos are surrounded by fluid. So when their cilia on both sides beat it creates a leftward flow that activates the Nodal cascade signalling pathway in a side specific manner that results in the breaking of symmetry. There are other physiologically controlled pathways used by animals that don’t use cilia. Here’s a good paper on that topic:
I would agree with much of your second point, however there are two points that I’m driving at, the first one is that the phenotype is the physiological state of cells, tissues, organs and organism. During ontology this physiological state is driven by the physics of cell and tissue movement, which in turn determines the range of possible gene expression. Since the gene expression is being driven by the physics of development the only way for evolution to change development sufficiently to directly impact the shape of an organism would be to alter the rate of cell growth. I don’t think that this is plausible for reasons that you can find in my answer to John Hartman.
As far as your third point is concerned I don’t think that lack of conservation is a reliable indicator of lack of function. A good example is the kinetochore, it is both highly functional and species specific. If you read my more detailed answer to John Hartman you can see that I am thinking about the entire cell as biomechanical machines and trying to reverse engineer their properties by thinking in terms of physics. The disagreement over which way of understanding embryology between Ernst Haeckel’s comparative anatomy, ( today comparative genetics) and Wilhelm His’ study of the proximal mechanical forces that construct the embryo lies at the root of our different understanding.
You are first going to have to show how mechanical pressures are inherited between generations and between species. This seems very unlikely to me. Without inheritance you have no explanatory power.
Incidentally, when you say “ontology” you mean “ontogeny”, and when you say “Hartman”, you mean “Harshman”.
Making that claim requires you to discount almost everything we know about gene regulation. Certainly there are effects from the cell environment, but aren’t there also effects from regulatory molecules? Some transcription factors are known to directly alter the rate of cell growth.
It’s a pretty good indicator, though, even if it’s not in every single case. But I’m not sure how this is relevant to your general hypothesis, whatever it may be.
By the way, changing the rate of cell growth is one of the simplest evolutionary changes, as the primary determinant of that is the speed with which the genome can be replicated. Simply changing the amount of genetic material up or down will affect the rate with which cells divide, be they part of multicellular tissues or just single cells. Changes in anything from intron length and number, to microsatellite DNA expansions or contractions, transposon or pseudogene copy numbers (deletion of unnecessary genetic material such as inactive retrotransposons or other long-dead pseudogenes), and so on, can all significantly contribute to both total genome size (and thus speed of cell division), or the rate of expression of individual genes.
This is an interesting idea. However, where is the evidence that physiology is inherently bistable?
Yes and the evidence is overwhelming, for a practical mathematical model of bistability during insect development I think a really good paper can be found here:
However, here is a simple everyday example. Take a breath, your breathing is governed by the about of CO2 that is in your blood when it rises beyond a certain level your brain triggers inhalation, (obviously the other state is exhalation). The Oxygen in the air diffuses through your lung’s alveolar cells into you blood where it displaces the CO2 that was attached to your hemoglobin ( bistability again) and delivers the O2 to your cells which replace it with CO2. Inside the cell the O2 is used to make ATP ( which is also bistable) which is recycled using a bistable ATP motor ( which is also bistable). This ATP is used to power a host of molecular machines that regulate cellular functions as you can see in the video below:
Are you referring to the signal of evolution?
No development, I think that the observation that gene transcription is reacting to many different mechanical forces that are not regulated by gene’s themselves makes it easier to understand why evolution doesn’t actually explain much about the origin of biological novelty, because gene don’t create most of the pressures that build embryos just like genes don’t control the motion of the molecular machines in the video that I showed earlier. So evolution defined as a change in gene frequencies can not directly impact sequential physical states that are created by cell movements. A good example of this sort of thing is mentioned will be mentioned my answer to John Hartman.
What is the scientific evidence that biomechanical systems are top-down? This assertion seems like a conjecture that a computer scientist unfamiliar with biology might make. Then again, I’m not a biologist so I’m not 100% sure.
Biological systems work from both the top down and the bottom up, for example in my example earlier you could explain the direction of causation the other way. You would be correct that breathing due to CO2 is regulated from the bottom up, if you are asleep but from the top down if you decide to go for a run and now have to breath more frequently. What I’m saying about early embryogenesis is that it is mostly a top down process, physiological states are what control gene expression.
There are certainly stochastic forces identified by the theory of evolution, but I doubt a biologist would characterize any of them as white noise. Again, that seems like a conjecture a computer scientist unfamiliar with biology might make.
I agree, but I have found that sometimes it’s better not to know exactly how things work, because it frees you up to ask questions that are considered to have been answered long ago. For example here’s an old interview with Sydney Brenner one of the scientists who was a pioneer of molecular biology, where he talks about it being surprising that biologists don’t understand the similarities between computer science and biology better:
I think the reason for this confusion is the obvious implications about what the origins of computation are.
I will be answering John Hartman’s question within the hour, I know that I have been directing everyone to an answer that I have not posted yet, that is only because I am trying to make it easy to understand with a logical progression of thought, something that can be a bit of a challenge for me at times, because I often don’t have to explain my thinking just what I have done. Also since my wife and I have small children I have limited time to post comments on the internet, I appreciate everyone’s patience.
And yet we know evolution has done so, because that is how humans have been able to select dogs with different cranial morphologies by affecting the rate of cell growth directly.
Abstract
Since the beginnings of domestication, the craniofacial architecture of the domestic dog has morphed and radiated to human whims. By beginning to define the genetic underpinnings of breed skull shapes, we can elucidate mechanisms of morphological diversification while presenting a framework for understanding human cephalic disorders. Using intrabreed association mapping with museum specimen measurements, we show that skull shape is regulated by at least five quantitative trait loci (QTLs). Our detailed analysis using whole-genome sequencing uncovers a missense mutation in BMP3 . Validation studies in zebrafish show that Bmp3 function in cranial development is ancient. Our study reveals the causal variant for a canine QTL contributing to a major morphologic trait.
Author Summary
As a result of selective breeding practices, modern dogs display a multitude of head shapes. Breeds such as the Pug and Bulldog popularize one of these morphologies, termed “brachycephaly.” A short, upward-pointing snout, a massive and rounded head, and an underbite typify brachycephalic breeds. Here, we have coupled the phenotypes collected from museum skulls with the genotypes collected from dogs and identified five regions of the dog genome that are associated with canine brachycephaly. Fine mapping at one of these regions revealed a causal mutation in the gene BMP3 . Bmp3’s role in regulating cranial development is evolutionarily ancient, as zebrafish require its function to generate a normal craniofacial morphology. Our data begin to expose the genetic mechanisms unknowingly employed by breeders to create and diversify the cranial shape of dogs.
And here:
https://www.sciencedirect.com/science/article/pii/S096098221730502X
Summary
In morphological terms, “form” is used to describe an object’s shape and size. In dogs, facial form is stunningly diverse. Facial retrusion, the proximodistal shortening of the snout and widening of the hard palate is common to brachycephalic dogs and is a welfare concern, as the incidence of respiratory distress and ocular trauma observed in this class of dogs is highly correlated with their skull form. Progress to identify the molecular underpinnings of facial retrusion is limited to association of a missense mutation in BMP3 among small brachycephalic dogs. Here, we used morphometrics of skull isosurfaces derived from 374 pedigree and mixed-breed dogs to dissect the genetics of skull form. Through deconvolution of facial forms, we identified quantitative trait loci that are responsible for canine facial shapes and sizes. Our novel insights include recognition that the FGF4 retrogene insertion, previously associated with appendicular chondrodysplasia, also reduces neurocranium size. Focusing on facial shape, we resolved a quantitative trait locus on canine chromosome 1 to a 188-kb critical interval that encompasses SMOC2 . An intronic, transposable element within SMOC2 promotes the utilization of cryptic splice sites, causing its incorporation into transcripts, and drastically reduces SMOC2 gene expression in brachycephalic dogs. SMOC2 disruption affects the facial skeleton in a dose-dependent manner. The size effects of the associated SMOC2 haplotype are profound, accounting for 36% of facial length variation in the dogs we tested. Our data bring new focus to SMOC2 by highlighting its clinical implications in both human and veterinary medicine.
So here the mutational causes of changes in gene-regulation (of a truly ancient developmental gene) are identified, which show how a change in rate of cell growth ultimately results from a mutation-caused change in the rate of gene expression during cranial development of dogs.
They’re both. Some regulatory element responds to an environmental cue, is “enabled”, leading to cell division. The dividing cell has now altered it’s own environment, as there’s two cells where before there was one. Each of these cells can now sense through some environmental cue that another cell is present. Which in turn affect how other genes are expressed, leading to enabling of some developmental pathway. And so on.
And yes, it is well-known that gene-regulation is sensitive to environmental stimuli in a way that produces a sort of developmental determinism, where regulatory events that happened multiple cell-divisions ago are partly the of causes particular regulatory events later.
So it would be incorrect to state both that changes in gene-expression are merely “associated” with particular physiological states, just as it would be incorrect to say that everything is only and exclusively the product of genes. The physical environment in which these genes exist (both inside and outside the cell) always needs to be considered to understand how and why particular gene expression patterns occur as they do, and change over time.
I think your confusion here partly derives from an overly simplistic view of gene regulation in response to physiological changes that emerge during development. You seem to be taking biologists’ view of gene-regulating to be sort of “blind” to circumstances, as if biologists think that some sort of genetic program enables and then just runs to completion with no feedback from the environment. I’m afraid this picture reveals your own misunderstanding rather than constituting an accurate description of how developmental (and evolutionary) biologists understand gene regulation in relation to development.
The offspring develops from a single cell. The mechanical pressures that develop as it divides again and again is a product of these consecutive cell divisions. These cell divisions are themselves the product of ongoing gene-regulation in response to environmental cues.
This seems quite confused. Mechanical pressures aren’t inherited, genes are. Thus the mechanical pressures must necessarily be caused by the genes, which produce their physical effects through their interactions with the environment as the organism develops. Of course, if the environmental cues to which the gene-regulatory elements respond are no longer present, then these regulatory reaction cascades won’t “run as normal”, or perhaps not even enable at all. And so again, it is no single thin in isolation that can be said to be the cause of why some organism develops the way it does.
They are not exclusively causally influenced by genes, but they are regulated in part by genes. There can be more than one contributing cause to some phenomenon. Without the gene encoding the receptor, or regulatory protein, the environment would not all by itself cause the genes downstream of the binding spot of the regulatory protein to become expressed.
Your mistake is to do what appears to be the diametrically opposite of an overly gene-centric view of development and gene expression, you seem to be focusing entirely on environmental factors and ignoring that these environmental factors must interact with genes that regulate other genes.
Yes they do, they are just multiple steps removed in the causal chain. The change in pressure is due to increases in the number of cells (for example). The change in the number of cells is due to multiple consecutive cell divisions. Why was there multiple consecutive cell divisions? Well because the gene-expression pattern resulting in cell division was turned on. And so on and so forth.
Genes are part of that system of control. Those genes of course interact with the intracellular and extracellular environment to regulate the action of that molecular machine, but it is wrong to point exclusively to external physical factors as the sole cause of why it does what it does, just as it is wrong to point only to some gene as a necessary and sufficient cause of it’s activity.
But of course it can. A transposition of a gene that codes for a protein that creates cell movement into an area of the genome under control of a different promoter that is active under different environmental conditions can do that.
I’m sorry but what you’re saying is just unambiguously wrong.
John I will be giving this reply a more detailed response asap, I originally planned on replying this morning but I am helping my wife with our 22 month old triplets today. Here’s an article that outlines some of the points I will discuss in my post later:
Minimally, could you stop misspelling my name?