Name It / Claim It: Epigenetics Now Just Another Evolutionary Mechanism

mike1962: You can’t or won’t provide any source code of your implementation for analysis. No sense reinventing the wheel. Reynolds already did it for you, along with countless others since. mike1962: I asked for source code from you, using any algorithm you like We provided evidence how a basic algorithm based on simple interactions between neighboring birds results in flocking behavior. This evidence is easily available to you. We can point it out to you, but we can't make you look. Not sure what you are trying to accomplish. Zachriel

Zachriel, I asked for source code from you, using any algorithm you like, so we can analyze how "simple" your implementation is. I can see why you would want to wave your hand to someone else's algorithm without actually implementing it, but that's not what I asked for. You can't or won't provide any source code of your implementation for analysis. So your real answer is: I can't do it, or I won't do it. Okie dokie. mike1962

mike1962: Where’s your source code? An algorithm was provided in Reynolds, Flocks, herds and schools: A distributed behavioral model, Computer Graphics 1987. Because it is an algorithm, it is independent of the implementation. Zachriel

Zachriel, Where's your source code? mike1962

gpuccio: Still waiting for the video. We provided evidence. You can ignore it, or grapple with it. The choice is yours. Zachriel

Zachriel: And the source code, obviously, behind the video. gpuccio

Zachriel: Still waiting for the video. gpuccio

mike1962: Not. Holding. Breath. Asked and answered. Zachriel

Not. Holding. Breath. mike1962

mike1962: You already said that. And you already asked that. Zachriel

Zachriel, You already said that. Apparently, you are having trouble following. mike1962

mike1962: If you want to lift someone else’s algorithms and source code that implements what you described as “flock and swarm behavior [that] is simple to simulate”, what gpuccio specified and what I asked for, I’m OK with that. The algorithm was provided in Reynolds, Flocks, herds and schools: A distributed behavioral model, Computer Graphics 1987. Zachriel

Zachriel: You are beyond hope. I am waiting for a video of your experiment with model airplanes. The pattern is encoded by the encoding of the individual behaviours and complex rules which will generate it. The foundation for the "inherited behaviors" is not understood. They are certainly not simple, and only when we know how they are written and inherited will you be able to exercise your imagination to try to explain how RV and NS generated the necessary biological information. Good luck! gpuccio

Zachriel: The vee-formation is a modification wherein the rule is to minimize energy by flying in the wake of the bird before it. I asked you for an "implementation" that is a "simple" (your word.) Can you do it or not? If you want to lift someone else's algorithms and source code that implements what you described as "flock and swarm behavior [that] is simple to simulate", what gpuccio specified and what I asked for, I'm OK with that. When will you be providing your source code for us to scrutinize for "simplicity"? (Not. Holding. Breath.) mike1962

gpuccio: And how are those “simple” rules implemented biologically? By utilizing already well-developed adaptations for the senses and for flight. gpuccio: because it understands that such a behaviour will give it advantages, or because something in its genome/epigenome forces it to do so? My point is that the second explanation is obviously correct. That's right. As with most complex vertebrates, they inherit some instinctual behaviors, then refine them through learning. gpuccio: I quoted “complex flight dynamics” and “complex sensory feedback” from the abstract of the Nature paper. Those tools are described there as necessary to accomplish the flight in formation. So is a respiratory system, mating habits, mitochondrial activity, etc. However, we're discussing how the pattern of the flock forms. The pattern self-organizes from a few basic rules of individual behavior. gpuccio: The “simple” rules you quoted are obviously aimed at achieving the flocking pattern. So, if they are encoded, their necessary outcome, the flocking pattern, is encoded too as an aimed result. No. The pattern is not encoded. The pattern is the result of the individual behaviors. However, the pattern is subject to natural selection, which means the inherited behaviors are subject to change over generations. mike1962: I would be interested in seeing Zachriel pull off an implementation of this “simply.” The seminal experiment is Reynolds, Flocks, herds and schools: A distributed behavioral model, Computer Graphics 1987. The vee-formation is a modification wherein the rule is to minimize energy by flying in the wake of the bird before it. Zachriel

gpuccio: a) Take a couple dozen model airplanes, b) Encode those three simple rules in some software in them, so that c) As soon as you start them flying, unguided, they can easily and effectively fly in a V formation equivalent to what we observe in birds. Then, and only then, we can measure how “simple” your rules are. I would be interested in seeing Zachriel pull off an implementation of this "simply." The ball's in your court, Zachriel (Not. Holding. Breath.) mike1962

Zachriel: "Separation – avoid crowding neighbors (short range repulsion) Alignment – steer towards average heading of neighbors Cohesion – steer towards average position of neighbors (long range attraction)" And how are those "simple" rules implemented biologically? You have not really answered my main question: "Why do individuals follow those rules? Where are they written?" You say: "Because flocking has a number of advantages, both as predator and as prey, and because the rules are simple and directly related to other behaviors, there is a clear evolutionary pathway" What do you mean? Are the rules, however simple or complex they are, written in the genome/epigenome or not? Does each bird: "avoid crowding neighbors" "steer towards average heading of neighbors" " steer towards average position of neighbors" because it understands that such a behaviour will give it advantages, or because something in its genome/epigenome forces it to do so? My point is that the second explanation is obviously correct. Evolutionary pathways, true or imagined, are not the issue here. We are not, at present, discussing how the pertinent information was generated. We are discussing the existence of such pertinent information in the genome/epigenome, which you seem so eager to deny or minimize, and how it is written there. You say: "You are confused. Flight precedes flocking." No, you are confused. I quoted “complex flight dynamics” and “complex sensory feedback” from the abstract of the Nature paper. Those tools are described there as necessary to accomplish the flight in formation. Here is, again, the pertinent part:

Here we show that individuals of northern bald ibises (Geronticus eremita) flying in a V flock position themselves in aerodynamically optimum positions, in that they agree with theoretical aerodynamic predictions. Furthermore, we demonstrate that birds show wingtip path coherence when flying in V positions, flapping spatially in phase and thus enabling upwash capture to be maximized throughout the entire flap cycle. In contrast, when birds fly immediately behind another bird—in a streamwise position—there is no wingtip path coherence; the wing-beats are in spatial anti-phase. This could potentially reduce the adverse effects of downwash for the following bird. These aerodynamic accomplishments were previously not thought possible for birds because of the complex flight dynamics and sensory feedback that would be required to perform such a feat

So, it seems that you are confused, not I. "The basic interactions are encoded, not the global flocking pattern. The global pattern emerges from the simple rules." You are really trying to defend the undefendable. The "simple" rules you quoted are obviously aimed at achieving the flocking pattern. So, if they are encoded, their necessary outcome, the flocking pattern, is encoded too as an aimed result. Regarding how simple they seem to you (but obviously not to the authors of the Nature paper, and certainly not to me), just try the following: a) Take a couple dozen model airplanes b) Encode those three simple rules in some software in them, so that c) As soon as you start them flying, unguided, they can easily and effectively fly in a V formation equivalent to what we observe in birds. Then, and only then, we can measure how "simple" your rules are. gpuccio

Origenes: your idea seems to be that since we can explain a V formation bottom up from the level of individual birds, we can also explain embryo development bottom up from the level of individual molecules (and ultimately fermions and bosons). No. Our position is that an argument that bottom-up directional organization is inconceivable is fallacious. gpuccio: 1) What are those basic rules? The seminal experiment is Reynolds, Flocks, herds and schools: A distributed behavioral model, Computer Graphics 1987. Reynolds used three simple rules for his "boids": Separation - avoid crowding neighbors (short range repulsion) Alignment - steer towards average heading of neighbors Cohesion - steer towards average position of neighbors (long range attraction) This shows how global patterns in flocks emerge from simple interactions between the birds. These have been extended by direct observation of various species. For instance, see Young et al., Starling Flock Networks Manage Uncertainty in Consensus at Low Cost, PLOS Computational Biology 2013. gpuccio: 2) Why do you believe that they are “basic”? Individuals following these basic rules regarding their neighbors shows how the global pattern can emerge. They are basic because they can then be modified to suit a particular niche or environment, such as starlings above. gpuccio: 3) Why do individuals follow those rules? Where are they written? Because flocking has a number of advantages, both as predator and as prey, and because the rules are simple and directly related to other behaviors, there is a clear evolutionary pathway. gpuccio: 4) Is the transmission of those rules (that is, information) genetic/ epigenetic, or are those rules learned each time de novo by each individual, for some incredible luck and talent? As with most complex vertebrates, they inherit some instinctual behaviors, then refine them through learning. gpuccio: 5) ... Do you believe that “complex flight dynamics” and “complex sensory feedback” are the result of a few “basic rules”? You are confused. Flight precedes flocking. The global pattern of the flock is due to the interaction between the individuals. gpuccio: 6) Do you think that learning to walk is based on a few “basic rules”? No. But we're not discussing learning to walk or learning to fly, but how flying organisms organize into flocks. gpuccio: Obviously, there is not an external supervisor which tells each bird how to fly. Good. gpuccio: The difference is that in a2) and c2) the coordination is due to genetic/epigenetic factors, and the behaviour is therefore specific of a species. This is the key. The basic interactions are encoded, not the global flocking pattern. The global pattern emerges from the simple rules. gpuccio: In no such cases a bottom up explanation can be proposed, because bottom up systems, where individuals simply make adjustments to their local conditions, as you suggest, generate situations like those I have given in the first part of my post #87 We know that global patterns can emerge from simple interactions. We can show it in silico, and we can observe it in vivo. Zachriel

Zachriel: As I really believe that you are confused here, I will try to explain my point even more clearly. Let's take the three examples of "Coordinated distributed decisions" which I have given in my post #87: a2) Fishes swimming in formation b2) A coreography c2) Birds flying in formation Now, it should be rather clear that there is one difference between examples 1 and 3, and example 2. The difference is that in a2) and c2) the coordination is due to genetic/epigenetic factors, and the behaviour is therefore specific of a species. In example b2), instead, the coordination is explicitly external (the coreographer). Humans as a species have many coordinated behaviours which are based on genetic/epigentic coordination (for example, walking, as you have suggested yourself). But some specific coreography is not an endowment of the species: humans do not all repeat a same coreography at particualr times. In cases a2) and b2) (as in all cases of specific repeated bevaviours based on species specificity) the coordination is obviously in the genome(epigenome. In cases b2) as in all cases of specific coordinated human activities which are not "instinctive" to the species) an external coordination, or an internal coordination by a specific individual (for example, in the design of art) is necessary. But in all cases, a coordination is present, and is responsible of the complex functional achievement. In no such cases a bottom up explanation can be proposed, because bottom up systems, where individuals simply make adjustments to their local conditions, as you suggest, generate situations like those I have given in the first part of my post #87: a1) Fishes swimming in aquarium b1) Passersby in a street c1) Birds (flying randomly) where no specific functional coordination can be observed. gpuccio

Zachriel: "The proximate cause is that some birds individually follow basic rules based on their relationship to their neighbors." Well, a few simple questions on that: 1) What are those basic rules? 2) Why do you believe that they are "basic"? 3) Why do individuals follow those rules? Where are they written? 4) Is the transmission of those rules (that is, information) genetic/ epigenetic, or are those rules learned each time de novo by each individual, for some incredible luck and talent? 5) Regarding the paper in Nature: "These aerodynamic accomplishments were previously not thought possible for birds because of the complex flight dynamics and sensory feedback that would be required to perform such a feat" Do you believe that "complex flight dynamics" and "complex sensory feedback" are the result of a few "basic rules"? Do you believe that "complex flight dynamics" and "complex sensory feedback" are the result of individual bottom up learning, or do you think they are based on genetic/epigenetic information?? 6) Do you think that learning to walk is based on a few "basic rules"? Are you aware of the extremely complex biological information which is necessary at the level of the body, the nervous system, and so on, to achieve that task? Do you think that information is learned each time by each new human? Or is it based on genetic/epigenetic information? Why do we walk while horses don't? You grossly equivocate on the meaning of "supervisor". Obviously, there is not an external supervisor which tells each bird how to fly. But there is an internal supervisor, the genetic/epigenetic information in the specie Geronticus eremita, which tells each individual how to behave, and gevies each individuals the tools to behave that way, so that a V formation is achieved, according to very complex laws of aerodynamics that none of the birds understands, but which are the foundation of that specific and complex genetic/epigenetic information in the species Geronticus eremita. That genetic/epigenetic information works top down to achieve the V formation. How can you doubt that? The simple fact that only some species can do that should be enough to convince you. You are free to believe that the genetic/epigenetic information was achieved in the course of natural history by the bottom-up magical process of neo darwinism. That is your faith, and I am OK with others' freedom to choose their personal faiths. But to argue that the V formation is each time the result of bottom-up mechanisms, and not of the top-down results of genetic/epigenetic information in the species, is complete folly, and I am really amazed that you insist on such a wrong concept. gpuccio

Zachriel, your idea seems to be that since we can explain a V formation bottom up from the level of individual birds, we can also explain embryo development bottom up from the level of individual molecules (and ultimately fermions and bosons). I find it absurd that you choose to compare birds with molecules, but to make the point you can also offer ice crystal formation. Next follows a well-known discussion about the differences between order (V formation / crystals) and organization (embryo development). And of course you will argue that the differences are gradual and not in kind. - - - Origenes

gpuccio: Excuse me, why do you think that some birds fly in such a complex and efficient formation, while others don’t? The proximate cause is that some birds individually follow basic rules based on their relationship to their neighbors. The ultimate cause is that it can lead to reproductive success, depending on the bird's niche. gpuccio: Do you think that they know the laws of aerodynamics? No more than a human has to know the laws of gravity in order to walk. The bird learns to find the sweet spot, where the effort is least, and in time with its forward neighbor. Nor is that a "supervising control" of flock formation. It's an individual behavior that results in birds flying at an angle to the wake of the bird in front. There is no "supervisor" that tells each bird where to go. It's bottom-up organization. gpuccio: Why and how do bees build behives? Not through a "supervising controller", but the collective action of individual bees following basic rules of interaction. It's easier to model with ants, but the principle is the same. It's bottom-up organization. gpuccio: The only possible explanation is the the genome-epigenome of those species has the information about the flight, the formation, and the roles. The innate instinct of the bird is to follow certain basic rules of flight. It is the individual actions that make the pattern. Again, flock and swarm behavior is simple to simulate. It's bottom-up organization. Zachriel

Zachriel: Are you out of your mind? "individuals making adjustments to their local conditions"??? Excuse me, why do you think that some birds fly in such a complex and efficient formation, while others don't? How do you think that they have "awareness of the spatial wake structures of nearby flock-mates, and remarkable ability either to sense or predict it"? Do you think that they know the laws of aerodynamics? Why and how do bees build behives? Why and how do beavers build dams? The problem of apparently very intelligent instinctive behaviour in animals is certainly unsolved, but how can you deny that it must have its foundation in genomic and epigenomic configurations? Bees don't learn each time how to build a hive. It's not that their personal intelligence, or intuition solves the problems involved. They behave that way instinctively, and therefore it is obvious that the behaviour has its foundation in their genomic and epigenomic constitution (information). When birds fly in a V formation, solving complex problems of aerodynamics, it's not because of their genius as engineers: they are programmed to do that way, and the interactions between them are obviously programmed: they happen in the same way for the same species. It's not that ibis build each time a different configuration, solving problems each time in a different way. The functional solution is in their genome and epigenome, it is not a sum of individual decisions: it is rather a sum of individuals applications of the same program, which is complex enough to include separate roles for individuals during the development of the procedure. Exactly like it happens in cell differentiation. How can you believe that this is the result of unguided bottom-up organization? Your idea has no sense, it is really not even a credible hypothesis. "individuals making adjustments to their local conditions"? Excuse me, the individuals have in principle the same genome-epigenome, with all possible inter-individual variations which are certainly nor aimed to get a V formation. Local conditions are certainly random and variable. They have no information about how birds can fly in a V formation. The individuals do not learn individually how to fly in formation. Some species do it, others don't. The formation implies different roles. The only possible explanation is the the genome-epigenome of those species has the information about the flight, the formation, and the roles. I cannot even begin to understand how you think that the outcome could regularly come from unguided "individuals making adjustments to their local conditions". I think that here you are really confused. gpuccio

gpuccio: Well, I dont know “what is the supervising control for an avian flight formation”. Nothing in what you posted indicates any evidence of a "supervising control". Rather, everything points to individuals making adjustments to their local conditions resulting in a global pattern, that is, bottom-up organization. This doesn't "prove" that embryogenesis is bottom-up organization — that would require looking at the details — but it does show that the argument that bottom-up organization can't occur is false. Zachriel

Zachriel: From Wikipedia:

Coordinated formation flight A wide variety of birds fly together in a symmetric V-shaped or a J-shaped coordinated formation, also referred to as an "echelon", especially during long distance flight or migration. This pattern of formation flying is resorted to so as to save energy and improve the aerodynamic efficiency of birds.[8] The birds flying at the tips and at the front interchange positions in a timely cyclical fashion to spread flight fatigue equally among the flock members. The wingtips of the leading bird in an echelon create a pair of opposite rotating line vortices. The vortices trailing a bird create an underwash which creates an induced drag for the bird creating it; at the same time these vortices create an upwash which can aid the flight of any bird following.[9] In a 1970 study the authors claimed that each bird in a V formation of 25 members can achieve a reduction of induced drag and as a result increase their range by 71%.[10] Studies of waldrapp ibis show that birds spatially coordinate the phase of wing flapping and show wingtip path coherence when flying in V positions, thus enabling them to maximally utilise the available energy of upwash over the entire flap cycle. In contrast, birds flying in a stream immediately one behind another do not have wingtip coherence in their flight pattern and their flapping is out of phase, as compared to birds flying in V patterns, so as to avoid the detrimental effects of the downwash due to the leading bird's flight.[11]

From Nature:

Upwash exploitation and downwash avoidance by flap phasing in ibis formation flight Nature, 2014, doi:10.1038/nature12939 Abstract: Many species travel in highly organized groups1, 2, 3. The most quoted function of these configurations is to reduce energy expenditure and enhance locomotor performance of individuals in the assemblage4, 5, 6, 7, 8, 9, 10, 11. The distinctive V formation of bird flocks has long intrigued researchers and continues to attract both scientific and popular attention4, 7, 9, 10, 11, 12, 13, 14. The well-held belief is that such aggregations give an energetic benefit for those birds that are flying behind and to one side of another bird through using the regions of upwash generated by the wings of the preceding bird4, 7, 9, 10, 11, although a definitive account of the aerodynamic implications of these formations has remained elusive. Here we show that individuals of northern bald ibises (Geronticus eremita) flying in a V flock position themselves in aerodynamically optimum positions, in that they agree with theoretical aerodynamic predictions. Furthermore, we demonstrate that birds show wingtip path coherence when flying in V positions, flapping spatially in phase and thus enabling upwash capture to be maximized throughout the entire flap cycle. In contrast, when birds fly immediately behind another bird—in a streamwise position—there is no wingtip path coherence; the wing-beats are in spatial anti-phase. This could potentially reduce the adverse effects of downwash for the following bird. These aerodynamic accomplishments were previously not thought possible for birds because of the complex flight dynamics and sensory feedback that would be required to perform such a feat12, 14. We conclude that the intricate mechanisms involved in V formation flight indicate awareness of the spatial wake structures of nearby flock-mates, and remarkable ability either to sense or predict it. We suggest that birds in V formation have phasing strategies to cope with the dynamic wakes produced by flapping wings.

Emphasis added. Well, I dont know "what is the supervising control for an avian flight formation". Neither seem scientists to know. It seems, however, as you can see, that it is some very complex sum of functions, certainly rooted in deep and complex genetic and epigenetic information. Whatever the explanation may be, it does not seem to be a "simple case". gpuccio

Origenes: Don’t get your hopes up The argument was raised that bottom-up relationships can't result in global organization. If you don't understand simple cases, then it's unlikely you would recognize more complex examples. Zachriel

Zachriel: What is the supervising control for an avian flight formation?

Don't get your hopes up, Zachriel. Whatever it is, it does not produce something that is ...

... even vaguely comparable to the complexity and functional order in C. elegans’ first division: http://www.wormbook.org/chapters/www_asymcelldiv.2/asymcelldiv.2.html [Gpuccio]

Origenes

gpuccio: http://betterphotography.in/wp-content/uploads/2011/05/v-formation-rajesh.jpg I think the concept is clear. In all the examples in the second set, some supervising control, based on specific information, gives order and function to the outcome. What is the supervising control for an avian flight formation? Zachriel

Origenes @90 Interesting comments. Dionisio

// follow-up #86 // The problem that materialism has with "function", is that it is cannot be understood in isolation, but requires the context of a larger whole instead. Legs, arms, head, muscles, organs, and cells are all functional to the whole. IOWs it is in conjunction with a whole that the parts make (functional) sense and are unified. Yet IOWs when we speak of "function" we explain the parts from the level of the whole. And obviously this in direct contradiction to the ambition of materialism. — Why does a cat have eyes? So it can see. — Here are some of the questions wrt function that spook materialists: Why would the parts be in functional submission to a larger whole? What is the bottom-up explanation for this top-down hierarchical relationship between the whole and the parts? We see a reflection of the same hierarchical whole-part-relationship in written language. One cannot explain the context (the message) in these sentences bottom-up from the level of the characters. Obviously, the characters lack the tools and intelligence to produce it. Instead each character is in "functional submission" to the (larger) context. The characters derive there functionality (meaning) from a higher level. NB as with biology, we observe several levels of contexts/wholes: words, sentences, paragraphs, stories. IOWs it is the context that explains the parts and not the other way upwards :) Origenes

Origenes @86 Good point. Dionisio

gpuccio @81-85,87 Wow! Eccellente! Juicy comments. Thank you! Dionisio

Zachriel: 1) Uncoordinated (or minimally coordinated) distributed decisions: a1) Fishes swimming in aquarium: http://www.welovedates.com/date-ideas/first-date-ideas/aquarium-date/ b1) Passersby in a street: http://visitbirmingham.com/files/2012-02-08/NewStreet-ET.jpg c1) Birds: http://www.pageresource.com/wallpapers/wallpaper/flying-birds-apple-animals-blue-sky.jpg 2) Coordinated distributed decisions: a2) Fishes swimming in formation: https://s-media-cache-ak0.pinimg.com/736x/54/17/ab/5417abbff9b7942a7219dc47d4558391.jpg b2) A choreography: http://assets7.capitalxtra.com/2016/05/the-royal-family-dance-crew-1454588979-article-0.png c2) Birds flying in formation: http://betterphotography.in/wp-content/uploads/2011/05/v-formation-rajesh.jpg I think the concept is clear. In all the examples in the second set, some supervising control, based on specific information, gives order and function to the outcome. Which is, I believe, the central concept in ID. And there is nothing here which is even vaguely comparable to the complexity and functional order in C. elegans' first division: http://www.wormbook.org/chapters/www_asymcelldiv.2/asymcelldiv.2.html gpuccio

Dionisio: Perhaps one reason why the number of biology research papers keeps increasing so fast has to do with their bottom-up approach to investigation? Sometimes don’t they seem barking up the wrong trees? Maybe that’s also why we see so many instances of expressions like “surprisingly” and “unexpectedly” in the biology research papers? What do they expect when they get so surprised by the discoveries they make?

I'm thoroughly convinced that a "bottom-up" view on biology doesn't make any sense. From the level of fermions and bosons one cannot explain the coherence and organization we find at higher levels — a flock of birds notwithstanding. IOWs biology is simply off-limits to true materialism. The only versions of materialism that can join the debate are the ones which incorporate "information", "function", "control", "instructions" and so forth. To his credit Zachriel rejects the acceptance of such teleological concepts, because he holds them to be incompatible with materialism. Origenes

Zachriel: 2) Instead, you seem to mean that the decision making, the control, is distributed. But in what sense? It is obvious that the decision making happens in different places and at different times, therefore in that sens it is distributed by default. And that is true also of computer software: decisions are taken in different parts of the processor, at different times. But you seem to imply something different. You discuss the example of the flock of birds. And you say: "Each member need only follow a few basic rules, and the result of these individual decisions result in a global pattern." So, you seem to say: there are separate decision makings in each cell, and they give a global pattern. And so? It is obvious that each cell makes its decisions. And it is obvious that the sum of individual decisions gives a global pattern. You cannot mean something so trivial. At the level of the individual cell, it is obvious that individual parts make their own decisions, and that the sum of individual decisions gives a global pattern in the cell. For example, let's consider the first asymmetric division of the C. elegans zygote: a) PAR-3, PAR-6, PKC-3 "decide" to be restricted the anterior cortex b) PAR-1 and PAR-2 "decide" to be restricted to the posterior cortex c) PAR-4 and PAR-5 "decide to remain distributed evenly throughout the cortex and the cytoplasm. And a lot of other decisions take place, involving many other "actors", just to prepare the first asymmetrical division which will generate two cells with a completely different destiny. But I think that the behaviour of the PAR complex is enough to give an idea. So, each PAR molecule takes individual decisions (obviously as a response to some signals), and there is no doubt that the sum of those decisions gives a global pattern. That's what happens in any software in any functional complex system, and more generally in any machine. In a spreadsheet software, decisions are distributed and give a global functional pattern. In a car engine, decisions are distributed and give a global functional pattern. Please. look well at the word "functional". Because you may well understand that, when decisions are distributed, the global pattern could well not be functional at all. The general principle is: a) When decisions are distributed and coordinated by some supervising program, or set of instructions, or whatever, they can well give a global functional pattern, corresponding to the information in the "supervising set of instructions". b) When decisions are distributed and they are not coordinated in any way by any supervising information, the resulting global pattern is random and not functional at all More about that in next post . gpuccio

Zachriel: Now, let's try to understand your repeated argument about "distribution". For example: a) "The decision-making apparatus that forms the global pattern is distributed throughout the entire system, which includes the genome and the epigenome" b) "A Turing Machine can simulate a branching process, but processes linearly. This is distinct from an oak tree, wherein decisions about branching are distributed." c) "So, the decision making is distributed." d) “The control is distributed through the process” I am not sure that I understand really what you mean, so I will make two different hypotheses (although I think that the second is probably the right one): 1) With "distributed" you mean that the information which controls the process in written in many different parts (of the genome and/or epigenome). Now, while this is certainly true, it is also certainly irrelevant. We know all too well that the information can be as fragmented as we like (see for example hard disks), but nothing changes, provided that the system can retrieve it correctly. So, I suppose that this is not what you mean. Let's go on (in next post). gpuccio

Zachriel: Let's go yo your post #69, where you are supposed to have answered my questions. Let's make it simple. My main question was: "If you look at some complex software in its machine language form, would you say that it is just a cascade of signals?" You give a comment as follows: "With computers there is a distinction between the processor and the memory of the computer." Is that an answer? No, it isn't. But let's imagine that it is an answer. Reasonably, then it should mean: "No, I would not say that it is just a cascade of signals, because with computers there is a distinction between the processor and the memory of the computer". As an answer, it really makes no sense. If you look at a software running in its machine language form, either you describe it as "just a cascade of signals", or you don't. It seems that you don't. Now, what is the reason for that? You say: in computers there is a memory and there is a processor. But, as I have said, even in cells there are memories (mainly the genome) and processors (the epigenome, the translation system, and so on). The memory (the genome) is read differently in hundreds of different ways according to epigenetic processing. So, where is the difference? My next question, strictly related to the first one, was: "Would you say that there is no set of instructions there?" You "answer": "Computers also generally make a distinction between the program and the data." And so? The cell does, too. You can well consider protein coding genes as "data", and all the rest, for example promoters, enhancers, regulatory RNAs, as "program". Where is the difference? And you have definitely not asnswered the real question, which I will ask again, with some more detail: Looking at a complex software running, of which you can only see the machine language form, you can see two different things: a) The information in machine language form b) The outcome of the running (what the computer does) So, let's say that you are not a machine language monster, and you cannot identify a "set of instructions" in the complex sequence of bits. But you see that the software behaves, for example, as a very good spreadsheet. My question is: "Would you say that there is no set of instructions there?" Yes or no, please. And then an explanation, if possible. To the third question, you comment: "Computers generally work sequentially" But that means nothing. Any algorithm can be more or less sequential, parallel, branching, but in the end each signal determines an outcome, so in a sense it can always be described as a cascade of signals. Again, where is the difference? More on distributed things in the next distributed post. gpuccio

Zachriel: "the control is distributed through the process" You keep using that word! I do not think it means what you think it means. :) More in next post. (With your permission, I will give a distributed answer) gpuccio

Origenes: "I like your argument. When we look at some complex software at the level of its machine language form, we no longer see instructions and things don’t make sense. Another view point (higher level language) from which things do make sense, is obviously a strong indication of what the software is. Similarly when we look at embryo development as a purely chemical series of events, as Zachriel proposes, things don’t make sense. How can this process work without being controlled? How is homeostasis maintained? It makes much more sense when we look at embryo development as a system with data and procedures." That's exactly my point! Strange that you have understood and expressed it so well, while Zachriel... :) gpuccio

Origenes @79

[...] unwilling to answer [...]

Well, it's even worse that that. Note that sometimes you've got links to silly movie clips as the only explanation some folks can come up with in response to serious challenging statements. Perhaps one reason why the number of biology research papers keeps increasing so fast has to do with their bottom-up approach to investigation? Sometimes don't they seem barking up the wrong trees? Maybe that's also why we see so many instances of expressions like "surprisingly" and "unexpectedly" in the biology research papers? What do they expect when they get so surprised by the discoveries they make? However, sometimes being surprised could be good too: I've been wonderfully surprised by amazing grace. Dionisio

Gpuccio: The whole cellular machine is an incredibly complex system where data and procedures are strictly interwoven, and while we understand something of data, we still understand very little of the procedures. But that’s exactly what can happen if we look at some complex software in its machine language form.

I like your argument. When we look at some complex software at the level of its machine language form, we no longer see instructions and things don't make sense. Another view point (higher level language) from which things do make sense, is obviously a strong indication of what the software is. Similarly when we look at embryo development as a purely chemical series of events, as Zachriel proposes, things don't make sense. How can this process work without being controlled? How is homeostasis maintained? It makes much more sense when we look at embryo development as a system with data and procedures. It's no surprise to me that Zachriel is unwilling to answer your questions. Origenes

Origenes: However there are some striking differences between a flock of birds and embryo development, to name but a few: the birds are interchangeable without disrupting the global flock pattern and although the flock pattern is orderly it lacks specificity and specified parts. Sure. There are vast differences. However, the example suffices to show that global structure doesn't require global command. gpuccio: Why have I the impression that you have not answered my questions in post #68, repeated in post #70? What's the integer number between 68 and 70? gpuccio: Why? As explain, the control is distributed through the process. gpuccio: The branching of an oak tree, which you seem to like so much, is no good model for cell differentiation. It's not a model, but an example of how local decisions can result in a global pattern. Origenes: There is no conceivable bottom-up explanation for the orchestration of this directionality. Inconceivable Zachriel

It is an obvious truth that during embryo development homeostasis (HS) needs to be maintained. Here I would like to argue that HS is not compatible with neither Zachriel’s view nor any materialistic view. When we ponder HS we quickly realize that: —- 1. HS implies orchestrated/coordinated directionality of all parts of the organism. 2. There is no conceivable bottom-up explanation for the orchestration of this directionality. Therefore (from 1 & 2) 3. An explanation for HS must stem from oneness at the level of the whole organism or beyond — which is in direct contradiction to the claims of materialism. Conclusion: HS is not compatible with materialism. Ad (1). If all cells follow their own trajectory there can be no overall coherence and hence no HS. So all the parts of an organism must be coherently aimed at performing HS. N.B. the organism is in a dynamic equilibrium, even a single cell can be said to be never the same during its life cycle, and therefore we witness a constant reshifting and refocusing wrt HS. Also note, during HS, the parts of the organism behave subordinate to the whole, which is obviously suggestive of a hierarchical relationship between whole and the parts. Ad (2). There is no “master-regulator-molecule” in the cell — DNA included — which can even in principle be a cause for a multicellular organism’s HS; any molecule simply operates at the wrong level to do so. Communication between cells is obviously helpful, but a “democracy of cells” cannot produce the dynamic decision-power combined with overview that is required wrt HS. —- HS constitutes a magnificent display of dynamic (living) unity at the macro-level for which there is zero explanation from the level of fermions and bosons. Even without the simple logic provided above, if an organism is a bag of chemicals, what on Earth would be able to keep the dynamic unity/coherence in place? Moreover, each (unpredictable) interaction with the environment (and sequence of interactions) is a threat to HS. Again, the assumption that HS is compatible with materialism ignores basic logic, ignores chemistry and ignores the tendency of the second law. Origenes

Zachriel: Why have I the impression that you have not answered my questions in post #68, repeated in post #70? About the comments that you have given: "You’re stretching the analogy too far." Why? "The decision-making apparatus that forms the global pattern is distributed throughout the entire system, which includes the genome and the epigenome." And so? That means only that the procedures are written in the global information in the genome and epigenome. And so? "This is distinct from an oak tree, wherein decisions about branching are distributed." The branching of an oak tree, which you seem to like so much, is no good model for cell differentiation. Branching can be a fractal process, more or less incorporating stochastic components. The branching of the respiratory tree, or of the vascular tree, can have some similarities to the branching of an oak tree. But cell differentiation is all another matter. Cells differentiate in specific phenotypes, completely different one from the other, and in specific places and times and relationships. That is extremely clear in C. elegans, where the 1000 or so cells are well known, and the differentiation process is well observed in every detail (observed, not understood!). When the C. elegans zygote makes its first asymmetric division, generating two completely different daughter cells through an incredibly complex process, there is no branching of anything: that's a complex program which is initiated and performed in that cell. And all the following divisions repeat the process, each time in completely different ways, and with completely different outcomes. Planned, controlled. I really don't understand your problem with instructions being "distributed". How should they be? Aren't instructions distributed in a running software? Isn't the constant exchange of information between the stored information and the recruited information in RAM and CPU memory what keeps the program running? This is so similar to what happens between genome and epigenome! Again, why am I "stretching the analogy too far"? "So, the decision making is distributed." There is a decision making that decides what transciption factors will be transcribed at a certain moment. That happens through other TFs, which regulate the transcription of the final TFs. Which have, as seen, different roles in initiating and maintaining some final transcriptome and phenotype. Acting through other epigenetic levels. Because, as you know, even those cis regulatory elements which bind the specific TFs are present in every cell. So, why do they work only in the right cell at the right moment? Maybe they are inhibited in other contexts. Maybe by methylation of the CpG islands in their promoter regions. Or by some histone code. The simple truth is that, at the right moment and in the right cell: a) The right TFs are expressed to express the final TFs b) The right cis elements are ready to bind them c) The right histone code is present in the appropriate places of the genome d) The right regulatory RNAs are expressed and spliced and processed to regulate the transcription e) and so on, and so on... This global process is different in each kind of cell, for each functional transition. It is in itself dynamic, and never completely the same, even in the same cell type, especially in stem cell pools. So yes, the decision making is distributed. The whole cellular machine is an incredibly complex system where data and procedures are strictly interwoven, and while we understand something of data, we still understand very little of the procedures. But that's exactly what can happen if we look at some complex software in its machine language form. So, will you answer my questions, or not? gpuccio

Zachriel: There is no program other than the cascade itself. It’s a sequence of events, each one triggering the next.

According to your view, everything that happens during embryo development, internal or external to cells, is neither controlled by an external program, nor information. So, there is nothing external to the sequence of events that steers the elements involved to their correct locations. IOWs the elements involved have to find their correct locations at the right time on their own. You explain how this works by the flock of birds analogy:

Zachriel:

Origenes: The flight pattern of a flock of birds is controlled by its parts (birds), because each bird is capable of considering its relationship to its neighbor.

That’s right. Each member need only follow a few basic rules, and the result of these individual decisions result in a global pattern.

Can you expand on your concept and this analogy? I can understand that a bird has the ability to keep a correct distance to its neighbors and also how this produces an orderly overall flock pattern. However there are some striking differences between a flock of birds and embryo development, to name but a few: the birds are interchangeable without disrupting the global flock pattern and although the flock pattern is orderly it lacks specificity and specified parts. Origenes

gpuccio @71

Curr Top Dev Biol. 2016;116:167-80. doi: 10.1016/bs.ctdb.2015.11.011. Epub 2016 Jan 23. Securing Neuronal Cell Fate in C. elegans. Zheng C, Chalfie M.

Very interesting paper. Thank you for posting the reference to it. BTW, I noticed some of your interlocutors seem to have difficulties understanding your clear comments? :) Dionisio

gpuccio: And in cells there is a disctinction between epigenome and genome. It’s the epigenome which processes the genome at each moment. You're stretching the analogy too far. The decision-making apparatus that forms the global pattern is distributed throughout the entire system, which includes the genome and the epigenome. gpuccio: And isn’t a computer algorithm often similar to a branching process? A Turing Machine can simulate a branching process, but processes linearly. This is distinct from an oak tree, wherein decisions about branching are distributed. gpuccio: Transcription factors control neuronal differentiation by acting as “terminal selectors” that determine the specific cell fates of different types of neurons. So, the decision making is distributed. Origenes: If I understand your position correctly, then, it seems to me, precise position of the elements involved is everything. Signaling is based on the relative position of the cells as they differentiate. This can be tested by bisecting or rearranging components during development. Origenes: The flight pattern of a flock of birds is controlled by its parts (birds), because each bird is capable of considering its relationship to its neighbor. That's right. Each member need only follow a few basic rules, and the result of these individual decisions result in a global pattern. Origenes: Are you saying that, similarly, embryo development is controlled by the parts/elements involved, because each element can (just like a bird) find its correct position on its own? Or differentiate in place. Zachriel

Zachriel,

Zachriel:

Origenes: Is the precise position at the right time, of the elements involved, critical to a correct unfolding of the sequence of events?

Generally so.

There is a certain laconic aspect to your answer, which I find surprising. If I understand your position correctly, then, it seems to me, precise position of the elements involved is everything. According to you, the information wrt embryo development is not externally specified, so it can be said to be embedded in the position of the elements. What else is there? Similarly, according to evolutionary theory, there is no external design of an organism, so the information can be said to be embedded in the fitness landscape. Am I correct? Here is my question again: Is the precise position at the right time, of the elements involved, critical to a correct unfolding of the sequence of events?

Zachriel:

Origenes: Does the ‘process’/’sequence of events’/’embryo development’ control itself?

Think of the flock example, and then try to answer the question yourself.

Zachriel: A very simple example is how a flock forms a flight pattern. You might think that to form a flight pattern, each bird would have to consider the formation of the pattern, but what really happens is that each bird just considers its relationship to its neighbor.

The flight pattern of a flock of birds is controlled by its parts (birds), because each bird is capable of considering its relationship to its neighbor. Are you saying that, similarly, embryo development is controlled by the parts/elements involved, because each element can (just like a bird) find its correct position on its own? Origenes

Zachriel: An example of programs: Curr Top Dev Biol. 2016;116:167-80. doi: 10.1016/bs.ctdb.2015.11.011. Epub 2016 Jan 23. Securing Neuronal Cell Fate in C. elegans. Zheng C, Chalfie M. Abstract Transcription factors control neuronal differentiation by acting as "terminal selectors" that determine the specific cell fates of different types of neurons. The specification of cell fate, however, requires high fidelity, which relies on stable and robust expression of the terminal selectors. Our recent studies in C. elegans suggest that a second set of transcription factors function as reinforcing or protecting factors to stabilize the expression and activity of terminal selectors. Some serve as "guarantors" to ensure the activation and continuous expression of the selectors by reducing stochastic fluctuations in gene expression; others safeguard the protein function of selectors by repressing inhibitors that would block their activity. These transcription factors, unlike the terminal selectors, do not induce specification but secure neuronal cell fate and provide reliability in differentiation. gpuccio

Zachriel: "With computers there is a distinction between the processor and the memory of the computer." And in cells there is a disctinction between epigenome and genome. It's the epigenome which processes the genome at each moment. "Computers also generally make a distinction between the program and the data." And in the cell there is a distinction between the program (the whole set of regulatory information, promoters, enhancers, non coding DNA, TADs, etc.) and the data (for example, the protein coding genes). "Computers generally work sequentially." Let me understand. Wasn't it you who looked at cell development as a sequence of cascades? And isn't a computer algorithm often similar to a branching process? It is not clear to me what your distinctions mean, and what value you give to them. However, I don't see that you have answered my main question, so I ask it again: Would you say that there is no set of instructions there? And just for clarity, I repeat the whole context: If you look at some complex software in its machine language form, would you say that it is just a cascade of signals? Would you say that there is no set of instructions there? Would you describe it as a branching process? Would you say that there is nothing external to the process itself controlling that sequence of events? gpuccio

Origenes: Does the ‘process’/’sequence of events’/’embryo development’ control itself? Think of the flock example, and then try to answer the question yourself. Origenes: Is the precise position at the right time, of the elements involved, critical to a correct unfolding of the sequence of events? Generally so. gpuccio: If you look at some complex software in its machine language form, would you say that it is just a cascade of signals? With computers there is a distinction between the processor and the memory of the computer. gpuccio: Would you say that there is no set of instructions there? Computers also generally make a distinction between the program and the data. gpuccio: Would you describe it as a branching process? Computers generally work sequentially. Zachriel

Zachriel: Just a question for you. If you look at some complex software in its machine language form, would you say that it is just a cascade of signals? Would you say that there is no set of instructions there? Would you describe it as a branching process? Would you say that there is nothing external to the process itself controlling that sequence of events? Just to understand your position. gpuccio

Zachriel:

Origenes: So, to be clear, embryo development, is “a sequence of events” and there is nothing controlling that sequence of events.

Nothing external to the process itself.

Does the 'process'/'sequence of events'/'embryo development' control itself? Is the precise position at the right time, of the elements involved, critical to a correct unfolding of the sequence of events? Origenes

Origenes: So, to be clear, embryo development, is “a sequence of events” and there is nothing controlling that sequence of events. Nothing external to the process itself. Origenes: So, the sequence of events, depends on the precise position of the elements involved and the presence of the elements themselves and nothing else? Part of the process is the exchange of messenger molecules, which helps cells determine their position within the whole. A very simple example is how a flock forms a flight pattern. You might think that to form a flight pattern, each bird would have to consider the formation of the pattern, but what really happens is that each bird just considers its relationship to its neighbor. https://businessnetworkswdotorg.files.wordpress.com/2015/03/geese-v-formation02.jpg Zachriel

Zachriel: There is no program other than the cascade itself. It’s a sequence of events, each one triggering the next.

So, to be clear, embryo development, is "a sequence of events" and there is nothing controlling that sequence of events. So, the sequence of events, depends on the precise position of the elements involved and the presence of the elements themselves and nothing else? Origenes

Origenes: So there is no epigenetic “program”. What would be a better term? We usually think of a program as a sequence of instructions acting on data. There is no program other than the cascade itself. It's a sequence of events, each one triggering the next. Origenes: Unfolding of what exactly? The sequence of events that results in development. So, in the most primitive bilaterians, there is an asymmetry between dorsal and ventral. This is then modified in more derived organisms so that distance from these poles determines additional differences. This is then modified into still more differences based on the relative position of neighboring cells. http://o.quizlet.com/i/LY8AJFFjsqUnXKHBXaS3Tg_m.jpg Zachriel

Zachriel,

Z: The word “program” is misleading.

So there is no epigenetic "program". What would be a better term?

Z: You’re thinking of it as something outside having an overview of the process.

No, I'm don't think that a program is capable of overview. However a program can sequence events.

Z: Rather, each step triggers the next steps in a branching pattern.

But there is no program or information that controls the sequence of the cascade?

Z: There is no overview (...),

Do you mean: "there is nothing controlling the cascade/embryo development"?

Z: (...) but an unfolding.

Unfolding of what exactly? Origenes

Origenes: Are you saying that the cascade — the embryo development — is controlled by an epigenetic program? The word "program" is misleading. You're thinking of it as something outside having an overview of the process. Rather, each step triggers the next steps in a branching pattern. There is no overview, but an unfolding. Origenes: Feel free to explain why the compatibility does not pose a conundrum for evolutionary theory. Again, we have little idea what you are asking. You might want to expand on your view somewhat. Zachriel

Zachriel:

Origenes: is it your position that this cascade — the embryo development — is controlled by a genetic program?

Embryogenesis is epigenetic, of course.

Are you saying that the cascade — the embryo development — is controlled by an epigenetic program?

Zachriel: Because your question presupposes that it poses a conundrum.

Feel free to explain why the compatibility does not pose a conundrum for evolutionary theory. Origenes

Origenes: is it your position that this cascade — the embryo development — is controlled by a genetic program? Embryogenesis is epigenetic, of course. Origenes: You again fail to respond to my question about Venter’s Syn 3.0, which I take as an admission that its compatibility with an existing epigenome poses a conundrum for evolutionary theory. Because your question presupposes that it poses a conundrum. Zachriel

Zachriel: Embryogenesis is essentially a single cascade,(...)

Thank you for this clarification. To clarify further: is it your position that this cascade — the embryo development — is controlled by a genetic program? - - - You again fail to respond to my question about Venter's Syn 3.0, which I take as an admission that its compatibility with an existing epigenome poses a conundrum for evolutionary theory. Origenes

Origenes: It is exactly this difference that eludes Zachriel’s understanding. In fact, we have been discussing the whole organism and embryogenesis. With embryogenesis, the process is via a cascade, not a step-by-step instruction manual. It's only by looking at the whole that the process can be understood. Origenes: Or perhaps he holds that there is one uninterrupted cascade? Embryogenesis is essentially a single cascade, however, one that is compounded by complexity. Origenes: These membrane targets provide crucial information—spatial coordinates—for embryological development. Sure. So? Origenes: Even so, my question, still stands. Z: Embryogenesis is a cascade. O: Are you saying that there is one uninterrupted cascade till death ... ? Z: Huh? We were discussing embryogenesis. O: My question still stands. Origenes: ... with no exact beginning? Embryogenesis begins when the egg is fertilized. Origenes: Is an organism something winding down like a wind-up clock? Aging is a different question, but it's clear that metazoan organisms do wind down; that is, they age; with telomeres being the clock. Zachriel

Zachriel: While we don’t know everything about embryonic development, the mapping of many of the basic signalings involved have been worked out, e.g. BMP4 involvement in dorsal-ventral asymmetry.

Here an example of non-basic signalings:

Another important source of epigenetic information resides in the two-dimensional patterns of proteins in cell membranes.18 When messenger RNAs are transcribed, their protein products must be transported to the proper locations in embryonic cells in order to function properly. Directed transport involves the cytoskeleton, but it also depends on spatially localized targets in the membrane that are in place before transport occurs. Developmental biologists have shown that these membrane patterns play a crucial role in the embryological development of fruit flies. Membrane Targets For example, early embryo development in the fruit fly Drosophila melanogaster requires the regulatory molecules Bicoid and Nanos (among others). The former is required for anterior (head) development, and the latter is required for posterior (tail) development.19 In the early stages of embryological development, nurse cells pump Bicoid and Nanos RNAs into the egg. (Nurse cells provide the cell that will become the egg—known as the oocyte—and the embryo with maternally encoded messenger RNAs and proteins.) Cytoskeletal arrays then transport these RNAs through the oocyte, where they become attached to specified targets on the inner surface of the egg.20 Once in their proper place—but only then—Bicoid and Nanos play critical roles in organizing the head-to-tail axis of the developing fruit fly. They do this by forming two gradients (or differential concentrations), one with Bicoid protein most concentrated at the anterior end and another with Nanos protein most concentrated at the posterior end. Insofar as both of these molecules are RNAs—that is, gene products—genetic information plays an important role in this process. Even so, the information contained in the bicoid and nanos genes does not by itself ensure the proper function of the RNAs and proteins for which the genes code. Instead, preexisting membrane targets, already positioned on the inside surface of the egg cell, determine where these molecules will attach and how they will function. These membrane targets provide crucial information—spatial coordinates—for embryological development. [S.Meyer, 'Darwin's Doubt', Ch. 14 The Epigenetic Revolution]

Origenes

Zachriel,

Gpuccio: So, there is a big differences between understanding specific parts of biological interactions, and understanding the whole picture, and how it is controlled.

Zachriel: .....

It is exactly this difference that eludes Zachriel's understanding. Or perhaps he holds that there is one uninterrupted cascade? Whatever the case may be, he doesn't want to say it.

Zachriel:

Origenes: As per usual, you speak in riddles, instead of clearly stating what you mean. So, I have to ask some more questions in order to get some clarity (sigh). Here goes … are you saying that there is one uninterrupted cascade till death with no exact beginning? Is an organism something winding down like a wind-up clock? Is that your concept?

We were discussing embryonic development, especially with regards to metazoa.

Even so, my question, still stands. And so does my question about the evolutionary explanation for the compatibility of an existing epigenome with Venter’s Syn 3.0 Origenes

gpuccio: That dose not appear to be a branching process The evidence is that it is a branching process. Development starts with basic differentiations that are inherited from very ancient ancestors; these are then successively modified during development. Origenes: are you saying that there is one uninterrupted cascade till death with no exact beginning? We were discussing embryonic development, especially with regards to metazoa. Zachriel

Zachriel:

Origenes: What controls when, where and how much of the signal that starts off a cascade?

One of the earliest is the differentiation between dorsal and ventral.

As per usual, you speak in riddles, instead of clearly stating what you mean. So, I have to ask some more questions in order to get some clarity (sigh). Here goes ... are you saying that there is one uninterrupted cascade till death with no exact beginning? Is an organism something winding down like a wind-up clock? Is that your concept?

Zachriel:

Origenes: Venter’s Syn 3.0 is a heavily modified ‘new’ genome which is compatible with an existing epigenome. What is the evolutionary explanation for the compatibility?

Still don’t know what you’re trying to say. It’s a stripped down genome. Why wouldn’t it be compatible?

The genome was not only stripped down, but also tidied up by reordering the remaining genes. Still the unmodified existing epigenome is able to work with the heavily modified genome. Why is that? Wouldn't you expect some cascade hiccups instead? What is the evolutionary explanation for the compatibility? Origenes

Zachriel: If information is stored, it is written. You can call it a set of instructions or not. The fact remains that you need complex configurations which give a specific result. If the result is a specific transcriptome and proteome in a differentiated cell which has definite functions, and a definite place in the body plan, then you need all those specific configurations that will make the stem cell become that differentiated cell at the right time and in the right place. Those configurations can be in the sequence of protein coding genes, or in non coding DNA, or in cytoplasmic components, or anywhere else: for what we know, as I have tried to say, a lot of different "signals", at various levels, are necessary and must be integrated for differentiation to happen. And remember, many different kinds of differentiation have to happen from the same original cell, at different time and space patterns. That dose not appear to be a branching process, rather the development of a carefully orchestrated program, whose complexity we are not yet able to understand. It's irrelevant that the information is written in what you would recognize as a "set of instructions" or not: the simple truth is that it acts as a set of instructions, but we don't know how it is written. gpuccio

gpuccio, image a collection of parts bins from which nothing is ever constructed, because there are no instructions for putting the parts to use. The cell manufactures the parts, but never "knows" what do do with them. they all "just happen" to function together. Pure magic. Mung

gpuccio: The only problem is that information can be “unfolded” only if it is written somewhere. That's a mathematical claim. The information has to be stored somehow, but it doesn't have to be stored as a written set of instructions. It's like how an oak tree grows. There's no instruction set about which branch to put where. Rather, there's a branching process. Origenes: What controls when, where and how much of the signal that starts off a cascade? One of the earliest is the differentiation between dorsal and ventral. Origenes: Venter’s Syn 3.0 is a heavily modified ‘new’ genome which is compatible with an existing epigenome. What is the evolutionary explanation for the compatibility? Still don't know what you're trying to say. It's a stripped down genome. Why wouldn't it be compatible? Zachriel

Mung: "We call that evolution." Great! :) gpuccio

Zachriel:

Origenes: Sure, but the question is: what controls when, where and how much of that “one signal”?

The previous signal. That’s what is meant by a cascade.

What controls when, where and how much of the signal that starts off a cascade?

Zachriel:

Origenes: How did natural selection prepare an existing epigenome for a new genome — modified by Venter?

Don’t understand your question.

Venter’s Syn 3.0 is a heavily modified ‘new’ genome which is compatible with an existing epigenome. What is the evolutionary explanation for the compatibility? Origenes

That’s exactly what happens in human software too. The only problem is that information can be “unfolded” only if it is written somewhere. We call that evolution. :) Mung

Zachriel: "You seem to think that the information is stored in a human-like fashion, with the events all written down in order somewhere." No, I don't think that. I simply think that the information is written somewhere and in some form, and that we don't know where it is. Wherever it is, it requires specific configurations of bits, like any form of information. "Rather, the information is unfolded in a cascade of events, each event triggering other events." That's exactly what happens in human software too. The only problem is that information can be "unfolded" only if it is written somewhere. Moreover, you know well that complex software requires not only sequential events, but also logical decisions, error checking, robustness, and so on. All those things require specific configurations of bits, IOWs, information, written somewhere in some form. Take, for example, the case of Induced pluripotent stem cells. We know that we can obtain them by adding a few transcription factors. Does that mean that we understand the process of de-differentiation? No. We just add the TFs, and wait. Time goes by (a few of weeks, usually), and with some luck a few of those precious stem cells are obtained. But we don't really know how that happens. So, there is a big differences between understanding specific parts of biological interactions, and understanding the whole picture, and how it is controlled. gpuccio

gpuccio: You say: another signal. OK, but as I said all signals are potentially there, in the genome. Choosing the correct signal in the correct cell at the correct time requires information. IOWs, epigenetic information is not so much in the signals themselves, but rather in the configuration of signals in space and time. You seem to think that the information is stored in a human-like fashion, with the events all written down in order somewhere. That's not how it works. Rather, the information is unfolded in a cascade of events, each event triggering other events. Zachriel

gpuccio: “Simple structures”? There is nothing simple in the zygote, or in stem cells. We're not referring to the individual cells, but to their differences, the differences which make up the metazoan bauplan; and while nothing is ever quite so simple in biology, the appellation of simple is reasonably applied to a differentiation that starts with a single cell type, then into two or three cell types and simple symmetries, then into many cells types with more complex relationships. gpuccio: Whatever you can say about trees, it is clear that just a sequence of genes or non coding genes which is common to all the cells in the organism is not likely to explain the ordered and specific development of different functional cell types, according to a body plan, unless specific configurations of information, in the sequence or elsewhere, are able to control the process. The information is unfolded in the cascade of events. Zachriel

Zachriel: "What we do know is that the developing organism starts with a few simple structures, which are then modified in increasing levels of specificity and diversity, and that this occurs through a cascade of signals." I don't understand what you mean. "Simple structures"? There is nothing simple in the zygote, or in stem cells. They are not "simpler" than a differentiated cell, only different. Indeed, in stem cells, at least at the level of histone code, most genes are in a double condition, of contemporary activation and inhibition. Differentiation usually implies the achievement of the final activated or repressed state by the appropriate genes for the cell type which is being generated. The problem, again, is: how is the decision about the correct development of "specificity and diversity" initiated and maintained, in different cells with different destinies? How are those different choices integrated into the correct body and tissue plan? Whatever you can say about trees, it is clear that just a sequence of genes or non coding genes which is common to all the cells in the organism is not likely to explain the ordered and specific development of different functional cell types, according to a body plan, unless specific configurations of information, in the sequence or elsewhere, are able to control the process. Can you say what those specific configurations are? How they work? IOWs, the question is not: is BMP4 a signal which is necessary to some specific differentiation process? but rather: why is that signal initiated in some specific cell, place and time? You say: another signal. OK, but as I said all signals are potentially there, in the genome. Choosing the correct signal in the correct cell at the correct time requires information. IOWs, epigenetic information is not so much in the signals themselves, but rather in the configuration of signals in space and time. gpuccio

Suppose that science can prove quantum entanglement of two particles inside the cell. As I understand it, such proof could be based on two empirical findings: 1. The coordinated spin of the two particles. 2. No conceivable local mechanism to account for the coordination. Now consider numerous entangled particles encapsulated by a cell membrane. However, in this case, “entangled” does not pertain to something banally simple as spin, but to homeostasis instead. That is, all the particles inside the cell are coherently aimed at keeping the cell alive — let’s call it 'homeostatic entanglement'. With homeostatic entanglement, just as with quantum entanglement like coordinated spin, we witness a coordinated directiveness of the particles involved. And just as with quantum entanglement there is no conceivable local mechanism to account for overall homeostatic entanglement. One may object by saying: but unlike spin we cannot scientifically measure something like “coherent directiveness towards homeostasis.” But I would reply that the health of the organism offers excellent opportunity for scientific measurements. Origenes

Origenes: Sure, but the question is: what controls when, where and how much of that “one signal”? The previous signal. That's what is meant by a cascade. gpuccio: Epigenetic regulations are not trees, they are parallel and integrated levels of intervention. Development unfolds in a treelike pattern. gpuccio: Each different tissue cell implements completely different groups of “cascades”. That's right. It's treelike. A few tissue types further differentiate. gpuccio: And please, consider the most important level of all (probably): the network of trascription factors. They do not work in cascade, but rather combinatorially. There is a basic structure as the zygote forms, then these structures are then modified, then those more detailed structures are further modified. This doesn't preclude that the final network may not be treelike. gpuccio: Do you really believe that having notions of how some isolated cascade works means understanding the general picture? What we do know is that the developing organism starts with a few simple structures, which are then modified in increasing levels of specificity and diversity, and that this occurs through a cascade of signals. gpuccio: This is about the combinatorial nature of TFs That's nice, but doesn't address the point; development occurring through a cascade of signals doesn't preclude a complex non-treelike network from forming. Origenes: How did natural selection prepare an existing epigenome for a new genome — modified by Venter? Don't understand your question. Zachriel

Dionisio: Very good contribution! And thank you for describing so well, at #39, those feelings which are very much my feelings too. :) gpuccio

gpuccio @33 @34 Very interesting reference links. Thank you. Dionisio

Origenes @30 Excellent question. Yes, at the core of it all we see lots of spatiotemporal decisions that seem to be choreographically in synch despite a very noisy stochastic environment with such an amazing robustness that defies our imagination. On one occasion while having lunch with a biology researcher who was telling me about his work, he suddenly paused and asked me if didn't like the food, suggesting we could order something else. I had not even touched my silverware yet, because my mind was trying to understand and imagine the amazing things he was describing about his research. Bottom line there was nothing wrong with the delicious food in that restaurant. It was all the professor's fault! :) Obviously he laughed out loud when I told him that. :) He said he wished his doc/post-doc students would give that kind of focused attention to his explanations. :) Well, doc and post-doc students have seen and heard much of what he was saying to me that day, hence they don't fall in the kind of 'awe' trance I was in. :) Besides, those of us who have been extensively and intensively exposed to information-processing systems and have worked on engineering design software development projects can't avoid having our imaginations fly uncontrollably when facing the detailed descriptions of biological systems seen these days in research papers. I have to humbly admit to being in such embarrassing situations on a number of occasions. :) What started as curiosity eventually became fascination and finally turned into an irresistible obsession that keeps me awake because time is very limited but the information we want to learn keeps growing exponentially. It's kind of like the situation experienced by a child left in the middle of a fantastic humongous toy/candy store. One just doesn't want to leave it even for a moment. :) We should motivate and encourage more young students to pursue biology research careers. And we should back any serious initiatives that lead to support the biology researchers who are truly dedicated to the advance of scientific knowledge to the benefit of all people. Dionisio

Origenes @35 Please, don't take me wrong, but perhaps your question seems a little premature in the sense that first we have to understand exactly how all that stuff works before they can try to figure out how we got it to begin with. As gpuccio mentioned, it doesn't seem like we're quite there yet. Work in progress... stay tuned. :) This is not Lego toys or Mickey Mouse stuff. We're seriously dealing with designed 'complex complexity' superior to any supercomputers or to a B787 / A350 (whichever you prefer) or to anything that we know of. Please, believe me, I'm looking forward, with increasing anticipation, to reading the latest research papers that shed more light on the elaborate molecular and cellular choreographies orchestrated within the biological systems. Biology research labs (both wet and dry) are generating an overwhelming amount of data that gradually is allowing us to get a better idea of the big picture. These seems fascinating times to watch (and support) serious scientific research specially in biology. Dionisio

#36 error correction: "...continuous from..." should read "...continuous form..." instead. Sorry for any confusion caused by that mistake. BTW, regarding the references to CISC and RISC, please let's note that the main discussions out there deal with comparing the pros/cons of those two main microprocessor architectures, but in any case we can't get away without some kind of fundamental instruction set to support the operating system of your choice or your preferred biological system. I think biological systems are based on a novel kind of CRISC architecture which combines the best of both CISC and RISC designs! :) Dionisio

gpuccio @31 My pleasure. But all I did was copy/paste what you wrote, so that readers, including some of your 'tough' interlocutors could read it again, but in a continuous from, without interruption, in order to understand the idea of your message correctly. BTW, can't wait to read the 'breakthrough' answers to your questions @32:

Each different tissue cell implements completely different groups of “cascades”. How is that achieved?

Do you really believe that having notions of how some isolated cascade works means understanding the general picture?

Those answers -assuming they're serious- might provoke true scientific headline news all over the scientific media! Lots of folks out there are seriously looking for exactly that. The best app software in the world won't do much outside a well designed operating system with the main regulatory clocks issuing the required impulses at correct intervals to activate the appropriate sets of circuits made of a bunch of interwoven logic gates and the established mechanisms to interpret the different app programs coded with that exact operating system in mind. Let's note that microprocessor architectures could be based on either complex or reduced instruction set computing (CISC or RISC) but in either case we deal with fundamental instruction sets that support the whole operating system (or the elusive biological 'procedure' controllers that obsess gpuccio so much that he keeps reminding us about them over and over again). Unless you take advantage of Xamarin, your software written on Visual Studio for a Windows OS won't do much in an Android or iOS machine. BTW, Xamarin has an important coming event named Evolve16, which proves that some evolution stories could be true at the end of the day. :) Legal Disclaimer: please note that I have no conflict of interest in mentioning Xamarin in my comment. I don't receive any kind of benefits from doing so and I'm not directly associated with Xamarin or MSFT. Dionisio

Zachriel, one more thing to consider: How did natural selection prepare an existing epigenome for a new genome — modified by Venter? Origenes

Zachriel: This is about the combinatorial nature of TFs: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2836267/pdf/nihms177825.pdf And, obviously, networks can partially lose control: http://bmcsystbiol.biomedcentral.com/articles/10.1186/1752-0509-6-61 gpuccio

Origenes: "Sure, but the question is: what controls when, where and how much of that “one signal”?" I think we perfectly agree on the main point here! :) The nature of such complex regulation networks eludes our understanding, much more than traditional biochemical cascades (see coagulation) or even classical membrane-to-nucleus signaling pathways (which are already complex enough, see for example this simplified figure for apoptosis: http://www.sabiosciences.com/images/Cellular_Apoptosis_Pathway_680.gif ). But, when we get to the nucleus, and to the network of TFs, the complexity increases exponentially. I have always been fascinated, for example, by the hugely complex interaction network of c-myc, one of the best studied transcription factors. Here is a "simple" figure about that from a paper about macrophages in immune response: The paper: http://journal.frontiersin.org/article/10.3389/fimmu.2014.00422/full The figure: http://www.frontiersin.org/files/Articles/101916/fimmu-05-00422-HTML-r1/image_m/fimmu-05-00422-g003.jpg Simple cascades? Not really! gpuccio

Zachriel: OK, but here we have lots of different and interconnected and alternative "cascades". And the epigenetic regulation is much more than the individual "cascades" which implement some particular effect. Epigenetic regulations are not trees, they are parallel and integrated levels of intervention. Stem cells exist in a continuous range of states, and in some way they find the correct balance between self renewal and differentiation. And this happens at multiple levels and at various stages, from the zygote down to adult stem cells. Each different tissue cell implements completely different groups of "cascades". How is that achieved? DNA methylation, histone post-translational modifications, chromatin remodeling, non coding RNAs of many different categories, all work in parallel. It is really difficult to understand in each situation what initiates what. Look at the recent thread about RNA-Directed DNA Methylation in plants: long and short non coding RNAs which modify the epigenetic status by DNA methylation! And please, consider the most important level of all (probably): the network of trascription factors. They do not work in cascade, but rather combinatorially. Some of the effects on chromatin status seem t be mediated by a complex of 10 - 15 TFs, or even more, acting together in connection with DNA, enhancers, promoters, and so on. Recent bioinformatic analyses of recent biological data allow to map the genome at multiple levels: the methylation state, the modifications of histones, enchancer and promoter status, 3D structure (TADs), and so on, and each of those levels has definite correspondences with functional states and cell types. Do you really believe that having notions of how some isolated cascade works means understanding the general picture? gpuccio

Dionisio: Wow! Thank you for working do much and so well on my posts! They look really fine this way. :) gpuccio

Zachriel:

Gpuccio: Do you really believe that “The signaling is the control”?

That is what signaling cascade means. One signal triggers the next; that is, the effect is the cause of the next event.

Sure, but the question is: what controls when, where and how much of that "one signal"? Origenes

gpuccio: Do you really believe that “The signaling is the control”? That is what signaling cascade means. One signal triggers the next; that is, the effect is the cause of the next event. This sort of network is consistent with evolution because they form a tree-like structure, wherein primordial switches are modified by future adaptations. Zachriel

gpuccio's excellent comments posted in this thread (this far) are literally textbook material and could be a separate new OP in UD: [I have used some 'artistic freedom' to make minor adjustments to the lyrics so that it fits within the melody, without changing the meaning of the author's message]

1. Epigenetics is a constant interaction between a static form of information (the nucleotide sequence stored in DNA, both protein coding and non coding) and its dynamic expression as transcriptomes and proteomes in each different cell state. In that sense, there is no condition in the cell life which is not at the same time genetic and epigenetic. For example, the zygote which originates multicellular beings has its own distinctive epigenetic state: the DNA is expressed in the zygote in different ways than it will be expressed in different states of the embryo, or in different specific tissue cells, both stem cells and differentiated cells. The epigenetic state of the zygote, in turn, is derived mainly from the cytoplasm of the oocyte, but also from epigenetic messages in the sperm cell. So, at each moment of the life of a cell, or even more of a multicellular being, the total information which is being expressed is a sum of genetic and epigenetic information. And, whatever you may think, any theory about the origin of biological information must explain how the total information content which is expressed during the life span of some biological being came into existence. 2. Does the actual “information” still rely on the DNA.? Not all of it, certainly. The cytoplasm, as I said, bears information too. And so does the state in which DNA is when it is transmitted in cell division. There is never a moment where DNA is in some “absolute” state. It is always in some epigenetic state. And the cytoplasm, or the nucleus itself as a whole, have specific information content at each state. The sum total of proteins and RNAs expressed, for example. As “life always comes from life”, life is always a continuous dynamic expression of genetic and epigenetic information. When Venter builds his “artificial” genomes, copying and modifying natural genomes, he has to put them into a living cell. IOWs, he is introducing a modified genetic component into a specific existing epigenetic condition. Remember, life is a dynamic, far from equilibrium condition, not a static storage of information. 3. Haven’t evolutionists known this for decades? Not exactly. The huge complexity of epigenetic networks, the whole complex and parallel levels which contribute to them (DNA methylation, histone code, topologically associated domains and dynamic 3d DNA structures, the various influences of different regulatory RNAs, the incredibly combinatorial complexity of transcription factors, the role of master regulators in differentiation, are all topics which have been “discovered” recently enough, and all of them are still really poorly understood. Whatever controls and coordinates the whole system of epigenetic regulations, moreover, is still a true mystery, be it in DNA or elsewhere. 4. I would like to mention here that epigenetics has at least two rather different aspects. One is the way that biological beings can interact with the outer environment, and then pass some information derived from that environment to further generations, through persistent epigenetic adaptations. This is what we could call the “Lamarckian” aspect of epigenetics. It is an aspect which is now well proven and partly understood, and it is certainly interesting. But, IMO, the truly revolutionary aspect of epigenetics is the complex network of regulations that allow different expressions of the same genome under different biological conditions, especially cell differentiation. That aspect has practically nothing to do with environment, either outer or inner, if we intend environment as something which is independent of the biological being, and which can modify its responses according to unpredictable, random influences. Indeed, this second aspect of epigenetics is all about information, and the management of information. IOWs, it’s the biological being itself which in some way guides and controls its own development. Now, you seem to believe that any form of such control must necessarily originate from the genome, because we have thought for a long time that the genome was the only depository of transmissible information. But today we know that the simple sequence of nucleotides in the genome is not enough. I will try to be more clear. In Metazoa, we have hundreds, maybe thousands, of different genomic expressions from the same genome. In the same being. How is that possible? DNA is a rather static form of information, in a sense: it is just a sequence of nucleotides. That sequence can be of extreme importance, but in itself it has no power. For example, even a protein coding gene is of no use if it is not “used” by the complex transcription / translation machinery. So, let’s say that we have a zygote. Let’s call its genetica information G1. G1 is not the basic DNA sequence which is the genome, but the specific DNA in the zygote condition, with all the modifications which make it partly expressed and partly inhibited, in different ways and grades. So, it is not “the genome”, but “one of the possible forms of the genome”. At the same time, the zygote has an active epigenome, in the cytoplasm and the nucleus, in the form of proteins (especially transcription factors), RNAs, and so on. IOWs, we have a specific transcriptome and proteome of the zygote, which we can call E1. So, we have: Zygote = G1 + E1 Now, the important point is that even in the “stable” condition of that zygote (IOWs, before any further differentiation happens) the flow of information goes both ways: from G1 to E1, and vice versa. The existing epigenome can and does modify the state of the existing genome, and vice versa. IOWs: G1 -> <- E1 Now, let's say that the zygote divides, and becomes two cells which are no more a zygote. IOWs, we have a division with some differentiation. Now, in each of the two daughter cells (in the simpler case of a symmetric division) there is a new dynamic state: G2 E2 Both the genomic state and the epigenomic state have changed, and that’s exactly what makes the daughter cell “different”: IOWs, cell differentiation. Now, the points I would like to stress are the following: 1) Any known and existing state of a living cell or being is always the sum of some G + some E. There is no example of any isolated G or E capable of generating a living being. 2) We really don’t know what guides the transition from any G1 + E1 state to the differentiated G2 + E2 state. We know much of what is involved in the transition, of what is necessary, and of how many events take place. But the really elusive question is: what kind of information initiates the specific transition, and chooses what kind of transition will happen, and regulates the process? Is it part of G1? Is it part of E1? Or, more likely, some specific combination of both? IOWs, I would suggest to consider as biological information not only the sequence of nucleotides in the basic genome, but also all the complex forms that G and E take in specific and controlled sequences. At any state, the information present is always the sum total of a specific G and a specific E, and never simply the basic genome G. Now, whatever you may think, or hope, the same evolutionary science that you invoke, and that has never been able to explain the origin of a single complex functional protein (but at least has tried), has really nothing to say about those epigenetic regulatory networks, for two very simple reasons: a) For the greatest part, we have no idea of where the information is, and it’s really difficult to explain what we don’t know and understand. b) The part that we know and understand (and it’s now a rather huge part) is simply too complex and connected [interwoven?] to even try any traditional explanation in terms of RV + NS. That is the simple situation. Science is a great and wonderful process, especially if it is humble, and tries to understand things instead of simply declaring that it can explain what it does not understand. 5. “Is it not utterly mysterious that an existing epigenome can cope with genomes modified by Venter?” Yes, it is. I am amazed each time I think of it. As it is amazing that the epigenome in the oocyte can cope with a differentiated nucleus in cloning experiments based on somatic cell nuclear transfer. The epigenome seems to be a very powerful entity, indeed. “Do you agree that DNA is not a conceivable candidate for controlling and/or coordinating the epigenome?” The only thing that I can say is that something controls and guides the G+E entity (the whole biological being), and that at present we really don’t know what it is and where the information that must be necessary for the process is written. We know too little. I usually sum it up with the old question: where and how are the procedures written? 6. I really think that the “master controller” of differentiation still eludes us. We know rather well a lot of epigenetic landscapes which correspond to differentiation procedures, and the role of many agents in those procedures. But still, it’s the “control” which eludes our understanding. IOWs, what decides the specific landscape which will be implemented in a specific moment, and what controls the correct implementation, through the correct resources? And how are the different scenarios implemented? The role of DNA is certainly important, but we still have to understand a lot about how DNA performs such a role. At present, we must assume that the sum of genome and epigenome at each moment has the information to achieve the correct destiny of the cell, and the tools to read and implement that information into specific epigenetic pathways. 7. I agree with you, and I am perfectly aware of how much has been discovered. Indeed, if you read my post #22, I state: “We know rather well a lot of epigenetic landscapes which correspond to differentiation procedures, and the role of many agents in those procedures. But still, it’s the “control” which eludes our understanding. IOWs, what decides the specific landscape which will be implemented in a specific moment, and what controls the correct implementation, through the correct resources?” The problem, as I see it, is that we are acquiring a lot of details about the pathways which are activated in various forms of differentiation, but we still cannot understand the control of those choices. In a software you can have many different functions, or objects, and then you have higher level procedures which use them according to some well-designed plan, which requires a lot of information. Both the information in the functions and objects and the information in the higher level procedures are needed. My point is simply that in biological differentiation we still don’t understand where the information about higher level procedures is, and how it works. There are some interesting concepts which are being proposed. For example, I am very intrigued by suggestions about how decisions about staminality and differentiation are made in cell pools, and how stem cells could work as a partially stochastic system to implement decisions. However, I still find that we understand very little about informational organization of cell differentiation, although I daily try to read new papers about that topic, hoping to find new hints. 8. Isn’t the signaling the control? No. The control is deciding when and how and how much [and where?] a signal must be implemented. The gene for BMP4 is always there, in the genome. All signals are potentially there. All transcription factors, and everything which can be potentially transcribed. The problem is: each epigenetic landscape is characterized by multiple and complex choices of signals. How can the cell “decide” and know which sequence of signals will be implemented at each time? How is the correct transcription of the BMP4 gene, and its translation, correctly implemented at the right time? What we know is essentially that some transcription factors or other molecule are necessary for some transition, and that they are expressed at the right moment, at the right place, and in the right quantity when that transition has to happen. But how is that achieved? That is a different question. The genome is a book which can be read in hundreds of different ways. There is purpose and information in the control of the ways it is read at each moment. There are hundreds or thousands of different signals, and only the right mix of them can work. Moreover, there must be flexibility, error correction, response to environmental stimuli, and so on. [robustness?] Do you really believe that only because we understand how some signals are involved in some processes we know how those processes are decided and controlled? Do you really believe that “The signaling is the control”? You, with all your understanding of informational problems? A signal is a control only when correctly used by a controller.

Dionisio

Zachriel: "You seem to be drawing a distinction without a difference. The signaling is the control." No. The control is deciding when and how and how much a signal must be implemented. The gene for BMP4 is always there, in the genome. All signals are potentially there. All transcription factors, and everything which can be potentially transcribed. The problem is: each epigenetic landscape is characterized by multiple and complex choices of signals. How can the cell "decide" and know which sequqence of signals will be implemented at each time? How is the correct transciprion of the BMP4 gene, and its translation, correctly implemented at the right time? What we know is essentially that some trascription factors or other molecule are necessary for some trnasition, and that they are expressed at the right moment, at the right place, and in the right quantity when that transition has to happen. But how is that achieved? That is a different question. The genome is a book which can be read in hundreds of different ways. There is purpose and information in the control of the ways it is read at each moment. There are hundreds or thousands of different signals, and only the right mix of them can work. Moreover, there must be flexibility, error correction, response to environmental stimuli, and so on. Do you really believe that only because we understand how some signals are involved in some processes we know how those processes are decided and controlled? Do you really believe that "The signaling is the control"? You, with all your understanding of informational problems? A signal is a control only when correctly used by a controller. gpuccio

gpuccio: The problem, as I see it, is that we are acquiring a lot of details about the pathways which are activated in various forms of differentiation, but we still cannot understand the control of those choices. You seem to be drawing a distinction without a difference. The signaling is the control. Zachriel

Zachriel: I agree with you, and I am perfectly aware of how much has been discovered. Indeed, if you read my post #22, I state: "We know rather well a lot of epigenetic landscapes which correspond to differentiation procedures, and the role of many agents in those procedures. But still, it’s the “control” which eludes our understanding. IOWs, what decides the specific landnscape which will be implemented in a specific moment, and what controls the correct implementation, through the correct resources?" The problem, as I see it, is that we are acquiring a lot of details about the pathways which are activated in various forms of differentiation, but we still cannot understand the control of those choices. In a software you can have many different functions, or objects, and then you have higher level procedures which use them according to some well designed plan, which requires a lot of information. Both the information in the functions and objects and the information in the higher level procedures are needed. My point is simply that in biological differentiation we still don't understand where the informatio about hogher level procedures is, and how it works. There are some interesting concepts which are being proposed. For example, I am very intrigued by suggestions about how decisions about staminality and differentiation are made in cell pools, and how stem cells could work as a partially stochastic system to implement decisions. However, I still find that we understand very little about informational organization of cell differentiation, although I daily try to read new papers about that topic, hoping to find new hints. gpuccio

gpuccio: a) For the greatest part, we have no idea of where the information is, and it’s really difficult to explain what we don’t know and understand. While we don't know everything about embryonic development, the mapping of many of the basic signalings involved have been worked out, e.g. BMP4 involvement in dorsal-ventral asymmetry. Zachriel

Gpuccio, your answers are again much appreciated.

GPuccio: But still, it’s the “control” which eludes our understanding. IOWs, what decides the specific landscape which will be implemented in a specific moment, and what controls the correct implementation, through the correct resources? And how are the different scenarios implemented?

And then there is the small matter of how, during all these changes, homeostasis is maintained. Does the organism-wide coherence we see not scream of higher overall control? What else can make sense of this display of unity? Instead of “decontextualizing” life by trying to identify how a ‘horizontal causality’ — one thing causing another — explains the organism, should we not start pondering on the existence of something that has the hierarchical power to contextualize the goings on in the cell? Origenes

Origenes: I really think that the "master controller" of differentiation still eludes us. We know rather well a lot of epigenetic landscapes which correspond to differentiation procedures, and the role of many agents in those procedures. But still, it's the "control" which eludes our understanding. IOWs, what decides the specific landnscape which will be implemented in a specific moment, and what controls the correct implementation, through the correct resources? And how are the different scenarios implemented? The role of DNA is certainly important, but we still have to understand a lot about how DNA performs such a role. At present, we must assume that the sum of genome and epigenome at each moment has the information to achieve the correct destiny of the cell, and the tools to read and implement that information into specific epigenetic pathways. gpuccio

Gpuccio, thank you. I'm reading up on the cloning by somatic cell nuclear transfer. Quick follow-up question: I rule out DNA as a master-controller for the following simple reason: if DNA is in control, and assuming that almost every cell in the human body has the same DNA sequence, why is a heart cell different from a brain cell? — Doesn't that suffice? Origenes

Origenes: "Is it not utterly mysterious that an existing epigenome can cope with genomes modified by Ventor?" Yes. it is. I am amazed each time I think of it. As it is amazing that the epigenome in the oocyte can cope with a differentiated nucleus in cloning experiments based on somatic cell nuclear transfer. The epigenome seems to be a very powerful entity, indeed. "Do you agree that DNA is not a conceivable candidate for controlling and/or coordinating the epigenome?" The only thing that I can say is that something controls and guides the G+E entity (the whole biological being), and that at present we really don't know what it is and where the information that must be necessary for the process is written. We know too little. I usually sum it up with the old question: where and how are the procedures written? gpuccio

Indiana Effigy: I certainly share your enthusiasm for the progress of science, but not for evolutionary "explanations". I would like to mention here that epigenetics has at least two rather different aspects. One is the way that biological beings can interact with the outer environment, and then pass some information derived from that environment to further generations, through persistent epigenetic adaptations. This is what we could call the "Lamarckian" aspect of epigenetics. It is an aspect which is now well proven and partly understood, and it is certainly interesting. But, IMO, the truly revolutionary aspect of epigenetics is the complex network of regulations that allow different expressions of the same genome under different biological conditions, especially cell differentiation. That aspect has practically nothing to do with environment, either outer or inner, if we intend environment as something which is independent of the biological being, and which can modify its responses according to unpredictable, random influences. Indeed, this second aspect of epigenetics is all about information, and the management of information. IOWs, it's the biological being itself which in some way guides and controls its own development. Now, you seem to believe that any form of such control must necessarily originate from the genome, because we have thought for a long time that the genome was the only depository of transmissible information. But today we know that the simple sequence of nucleotides in the genome is not enough. I will try to be more clear. In Metazoa, we have hundreds, maybe thousands, of different genomic expressions from the same genome. In the same being. How is that possible? DNA is a rather static form of information, in a sense: it is just a sequence of nucleotides. That sequence can be of extreme importance, but in itself it has no power. For example, even a protein coding gene is of no use if it is not "used" by the complex transcription / translation machinery. So, let's say that we have a zygote. Let's call its genetica information G1. G1 is not the basic DNA sequence which is the genome, but the specific DNA in the zygote condition, with all the modifications which make it partly expressed and partly inhibited, in different ways and grades. So, it is not "the genome", but "one of the possible forms of the genome". At the same time, the zygote has an active epigenome, in the cytoplasm and the nucleus, in the form of proteins (especially transcription factors), RNAs, and so on. IOWs, we have a specific transcriptome and proteome of the zygote, which we can call E1. So, we have: Zygote = G1 + E1 Now, the important point is that even in the "stable" condition of that zygote (IOWs, before any further differentiation happens) the flux of information goes both ways: from G1 to E1, and vice versa. The existing epigenome can and does modify the state of the existing genome, and vice versa. IOWs: G1 -> <- E1 Now, let's say that the zygote divides, and becomes two cells which are no more a zygote. IOWs, we have a division with some differentiation. Now, in each of the two daughter cells (in the simpler case of a symmetric division) there is a new dynamic state: G2 E2 Both the genomic state and the epigenomic state have changed, and that's exactly what makes the daughter cell "different": IOWs, cell differentiation. Now, the points I would like to stress are the following: 1) Any known and existing state of a living cell or being is always the sum of some G + some E. There is no example of any isolated G or E capable of generating a living being. 2) We really don't know what guides the transition from any G1 + E1 state to the differentiated G2 + E2 state. We know much of what is involved in the transition, of what is necessary, and of how many events take place. But the really elusive question is: what kind of information initiates the specific transition, and chooses what kind of transition will happen, and regulates the process? Is it part of G1? Is it part of E1? Or, more likely, some specific combination of both? IOWs, I would suggest to consider as biological information not only the sequence of nucleotides in the basic genome, but also all the complex forms that G and E take in specific and controlled sequences. At any state, th information present is always the sum total of a specific G and a specific E, and never simply the basic genome G. Now, wahever you may think, or hope, the same evolutionary science that you invoke, and that has never been able to explain the origin of a single complex functional protein (but at least has tried), has really nothing to say about those epigenetic regulatory networks, for two very simple reasons: a) For the greatest part, we have no idea of where the information is, and it's really difficult to explain what we don't know and understand. b) The part that we know and understand (and it's now a rather huge part) is simply to complex and connected to even try any traditional explanation in terms of RV + NS. That is the simple situation. Science is a great and wonderful process, especially if it is humble, and tries to understand things instead of simply declaring that it can explain what it does not understand. gpuccio

Gpuccio, thank you for your insightful comments.

Gpuccio: Epigenetics is a constant interaction between a static form of information (…) For example, the zygote which originates multicellular beings has its own distinctive epigenetic state: the DNA is expressed in the zygote in different ways than it will be expressed in different states of the embryo, or in different specific tissue cells, both stem cells and differentiated cells. (…) Remember, life is a dynamic, far from equilibrium condition, not a static storage of information.

Gpuccio: When Venter builds his “artificial” genomes, copying and modifying natural genomes, he has to put them into a living cell. IOWs, he is introducing a modified genetic component into a specific existing epigenetic condition.

Is it not utterly mysterious that an existing epigenome can cope with genomes modified by Ventor?

Gpuccio: Whatever controls and coordinates the whole system of epigenetic regulations, moreover, is still a true mystery, be it in DNA or elsewhere.

Do you agree that DNA is not a conceivable candidate for controlling and/or coordinating the epigenome? Origenes

GP, that is essentially what I said. We have known for decades that the environment (internal and external) can affect how the phenotype is expressed. How this happens, the examples you are providing above, is what has been discovered more recently. For example, we have known for a very long time that the sex of a turtle is dependent on the temperature it is incubated at. Clownfish are all born male and only the largest in a group will become female. Both of these are examples of how the exact same DNA will express different phenotypes dependent on environmental cues. The knowledge that this occurs is not new. The knowledge of how it works is. This is an excellent example of how effective and productive the evolutionary science community is. They were observing phenomenon that appeared to be counter to evolutionary understanding at the time. But rather than ignore it, they hypothesized, they, investigated, they experimented, and they came up with some of the answers. And they modified their understanding of evolution accordingly. Science at its best. I would like to thank News for posting this OP. But I suspect that she did not know that it was an excellent example of evolutionary science in action. Indiana Effigy

Indiana Effigy: "But evolutionists have known this for decades." Not exactly. The huge complexity of epigenetic networks, the whole complex and parallel levels which contribute to them (DNA methylation, histone code, topologically associated domains and dynamic 3d DNA structures, the various influences of different regulatory RNAs, the incredibly combinatorial complexity of transcription factors, the role of master regulators in differentiation, are all topics which have been "discovered" recently enough, and all of them are still really poorly understood. Whatever controls and coordinates the whole system of epigenetic regulations, moreover, is still a true mystery, be it in DNA or elsewhere. gpuccio

Indiana Effigy: "But if I am reading you correctly, the actual “information” still relies on the DNA." Not all of it, certainly. The cytoplasm, as I said, bears information too. And so does the state in which DNA is when it is transmitted in cell division. There is never a moment where DNA is in some "absolute" state. It is always in some epigenetic state. And the cytoplasm, or the nucleus itself as a whole, have specific information content at each state. The sum total of proteins and RNAs expressed, for example. As "life always comes from life", life is always a continuous dynamic expression of genetic and epigenetic information. When Venter builds his "artificial" genomes, copying and modifying natural genomes, he has to put them into a living cell. IOWs, he is introducing a modified genetic component into a specific existing epigenetic condition. Remember, life is a dynamic, far from equilibrium condition, not a static storage of information. gpuccio

GP: "It’s not that simple." Things sediment are. But if I am reading you correctly, the actual "information" still relies on the DNA. And that its expression is affected by the environment (internal and external to the cell). But evolutionists have known this for decades. In some ways it is part of the nature vs nurture debate. What is being discovered is how this actually happens. Indiana Effigy

Indiana Effigy: It's not that simple. Epigenetics is a constant interaction between a static form of information (the nucleotide sequence stored in DNA, both protein coding and non coding) and its dynamic expression as transcriptomes and proteomes in each different cell state. In that sense, there is no condition in the cell life which is not at the same time genetic and epigenetic. For example, the zygote which originates multicellular beings hai its own distinctive epigenetic state: the DNA is expressed in the zygote in different ways than it will be expressed in different states of the embryo, or in different specific tissue cells, both stem cells and differentiated cells. The epigenetic state of the zygote, in turn, is derived mainly from the cytoplasm of the oocyte, but also from epigenetic messages in the sperm cell. So, at each moment of the life of a cell, or even more of a multicellular being, the total information which is being expressed is a sum of genetic and epigenetic information. And, whatever you may think, any theory about the origin of biological information must explain how the total information content which is expressed during the life span of some biological being came into existence. gpuccio

"Excuse, but I thought that ‘epigentics’ is an open ended kind of term for postulated for a mechanism of information residing in structures yet to be identified, and not including DNA." Yes, I believe that is its definition. But if you want to go by that strict definition then there are no real examples of epigenetics. All examples, to the best of my knowledge, require the expression of information stored in the DNA. Under one condition the DNA is expressed in one way, under a different condition (eg. Methylation) the DNA is expressed in a different way. Please correct me if I am wrong. I have only recently started to read up about this subject. Indiana Effigy

effigy: Epigenetics is just the ability for the same stretch of DNA to be expressed in two different ways depending on the environment. Both phenotypic expressions can be acted on by selection pressures When you say "just" the ability does this mean your definition is the only one? Excuse, but I thought that 'epigentics' is an open ended kind of term for postulated for a mechanism of information residing in structures yet to be identified, and not including DNA. You know I always enjoy these terms invented by evolutionists, like "selection pressure" for quantities that can't be seen or measured or even visualized, yet the field is as well established as gravity which certainly can be measured. So it is said. groovamos

Quote - "Just a small correction. This was posted by Louis Savain (aka Mapou). It is interesting that both he and Joe, who are banned here, have resurfaced on Cornelius’ blog." Here is the problem I have with this subject even being brought up over here at the very beginning in this post in this forum. Why ? No real discussing on the fascinating mechanism of epigenetics is being done here. I agree that this JoeG and Louis S who ever they are shouldn't be producing the behavior they are in the discussion of any kind, but your side's debaters with the ever changing avatar sock-puppets over there aren't any better than the JoeGs or Mapous are. To take one example, I actually did some homework on one of the main hidden characters over there from your side, Mr Ghostrider, who apparently has used other cloaks in the past and present. "Thorton" and from what others have said "Occam's Aftershave" on another forum. The putrid behavior of this indiidual is on equal par with any JoeG or Mapou you cite as examples of improper etiquette, but you avoid any mention of your side's dirt and instead insert it into this discussion in this forum which stifles intelligent discussion. You want to play hometown Referee, but you need to call it both ways here Ref. But as I said, this was about deflection more than anything of inport on the subject posted. Epigenetics is an incredible subject on actual mechanisms for change which I guarantee you is going to replace your religious icon of random mutation and natural selection in the near future. Science will not be able to move ahead and innovate if they stay stuck in an obsolete Victorian Era religious doctrine. earthsinterface

Groovamos: "Now there is a real information-laden post for you. " I didn't think that any more information was needed. The inference is very obvious. Epigenetics is just the ability for the same stretch of DNA to be expressed in two different ways depending on the environment. Both phenotypic expressions can be acted on by selection pressures. Indiana Effigy

Groovamos: "Joe G via Effigy “Two Christophobic, dirt-worshipping, closet gay atheists having a pussy-cat fight on a Christian blog. LOL!..." Just a small correction. This was posted by Louis Savain (aka Mapou). It is interesting that both he and Joe, who are banned here, have resurfaced on Cornelius' blog. Indiana Effigy

Joe G via Effigy “Two Christophobic, dirt-worshipping, closet gay atheists having a pussy-cat fight on a Christian blog. LOL! Why don’t you two daffodils scurry on back to that gay atheist site, antievolution.org, where you belong. LOL Oops! Never mind. For a minute there, I plum forgot that your homosexual obsession is with Christian heterosexual males.” This is one contributor over there who I think needs a serious talking to and a probationary period before a possible ban. In fairness though his worst posts are opposing someone worse, the notorious thorton, aka ghostrider, who calls people fart smellers and worse and got banned before coming back with a new alias. I assume thorton's worst posts were pretty bad because they got deleted before I could read them, preceding and up to his ban. And BTW thorton/ghostrider is a researcher in the life sciences; Joe G. is apparently not an academic like many here are. Now understand that Joe G calling someone gay cannot be construed as pejorative nowadays, nor accusing them of homosexual obsession rather than any sexual obsession. And I can say this because I typically obliterate leftists on Facebook and of course they call me names, and in this vituperative spirit a couple of times I've been called 'gay' by these PC geniuses. In fact I have discovered recently that if I feel 'gay' I can be 'gay', as the current cultural overseers have declared, in general terms, such that the law must now recognize. And so I am about to embark on a gay journey. And will let you know how the leftist FB coterie take it. groovamos

Effigy: Epigenetics is still genetics. They don’t exist without DNA, which is subject to random mutation and affected by natural selection. Now there is a real information-laden post for you. 'Genetics' with a modifier prefix is still genetics - wow who would ever know that if it weren't for Darwinists. And "they [genetics] don't exist without DNA" is profound too, OMG. Since without DNA the planet would be a desert. Hey all geniuses hand clapping for Effigy - epigenetics is commonly meant to refer to the generation of form and function by via information residing outside the genome, with genome understood as being DNA stored information. Without DNA it wouldn't exist of course, duh. groovamos

Effigy Do you feel offended? Do you need a safe space? Eugen

Epigenetics is still genetics. They don't exist without DNA, which is subject to random mutation and affected by natural selection. Indiana Effigy

"It is often said that all truth passes through three stages. First, it is ridiculed. Second, it is violently opposed. Third, it is accepted as being self-evident. And so it is with epigenetics which evolutionists opposed and blackballed for a century before finally appropriating it as just another mode of evolutionary change." Why even pursue a deep intelligent discussion of Epigenetic mechanisms when you have Science Journals providing daycare fables on how blind undirected forces in a pointless universe work https://www.sciencedaily.com/releases/2016/04/160419083243.htm earthsinterface

"Maybe UD should think about allowing such insightful and informative comments to be posted here." It cuts both ways over there, but I noticed you conventiently left that out and avoided the subject of epigenetics altogether. The opposing side over there has a longer history of deflecting from the subject and instead prefers throwing mockery, personal insults and foul language since almost the beginning of his blog. But again you conveniently left that out. As far as "Epigenetics", if one goes back through articles and posted comments throughout the internet several years back, evolutionists were rabid opponents on the subject of such mechanisms which made their precious "Random Mutation & Natural Slection" religious icons out as false dieties. The comments were mostly vicious. But suddenly now it's all well lookie here, WWe new about Epigenetics all along and it's an amazing part of evolutionary change." Except not really. Believing it goes beyond what is observed is once again a matter of blind faith. earthsinterface

Dr. Hunter posts concurrent OPs here and on his own site. I just thought that people would like to see the types of comments that Dr. Hunter encourages and supports on his site. "Two Christophobic, dirt-worshipping, closet gay atheists having a pussy-cat fight on a Christian blog. LOL! Why don't you two daffodils scurry on back to that gay atheist site, antievolution.org, where you belong. LOL Oops! Never mind. For a minute there, I plum forgot that your homosexual obsession is with Christian heterosexual males." Maybe UD should think about allowing such insightful and informative comments to be posted here. Just a suggestion. Indiana Effigy