Origins codes for DNA: Argument for design?

_{Denyse O'Leary

November 13, 2015

Design inference, News}

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Here’s the abstract:

To unveil the still-elusive nature of metazoan replication origins, we identified them genome-wide and at unprecedented high-resolution in mouse ES cells. This allowed initiation sites (IS) and initiation zones (IZ) to be differentiated. We then characterized their genetic signatures and organization and integrated these data with 43 chromatin marks and factors. Our results reveal that replication origins can be grouped into three main classes with distinct organization, chromatin environment, and sequence motifs. Class 1 contains relatively isolated, low-efficiency origins that are poor in epigenetic marks and are enriched in an asymmetric AC repeat at the initiation site. Late origins are mainly found in this class. Class 2 origins are particularly rich in enhancer elements. Class 3 origins are the most efficient and are associated with open chromatin and polycomb protein-enriched regions. The presence of Origin G-rich Repeated elements (OGRE) potentially forming G-quadruplexes (G4) was confirmed at most origins. These coincide with nucleosome-depleted regions located upstream of the initiation sites, which are associated with a labile nucleosome containing H3K64ac. These data demonstrate that specific chromatin landscapes and combinations of specific signatures regulate origin localization. They explain the frequently observed links between DNA replication and transcription. They also emphasize the plasticity of metazoan replication origins and suggest that in multicellular eukaryotes, the combination of distinct genetic features and chromatin configurations act in synergy to define and adapt the origin profile. (paywall) – Christelle Cayrou, Benoit Ballester, Isabelle Peiffer, Romain Fenouil, Philippe Coulombe, Jean-Christophe Andrau, Jacques van Helden & Marcel Méchali.Genome Research, 11 November 2015.

These researchers’ findings make the genome sound like a committee, but without the usual duds, drones, and discards from more productive work groups that most human committees feature.

Thoughts?

Comments

Box: I’m afraid the bald claim stems from you, or rather naturalism. To which you reply with another bald claim. Box: it goes against basic reason. Rather, it goes against your incredulity — not the same thing at all.Zachriel_{November 19, 2015
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Zach: Well, then we’re just left with your bald claim.
I’m afraid the bald claim stems from you, or rather naturalism. And I would like to go even further, and state that the naturalistic claim that the astounding coordinated effort of millions of individual blind DNA strings that bring about a multicellular organism, which makes a performance of St. Matthew Passion by the Berlin Philharmonic Orchestra pale in comparison, does NOT need a level of coordination over and beyond the individual DNA strings is beyond bald; it goes against basic reason.Box_{November 19, 2015
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Box: If I’m right and there is a higher level of control Conditional. Box: — and indeed there has to be — If there has to be, then it follows deductively, but you've provided nothing more than 'It's astonishing, how could it not!' Box: then this level ceases its activity at the moment of death. Tautology. Death is defined as the cessation of living activity.Zachriel_{November 18, 2015
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Zach: Well, then we’re just left with your bald claim.
If I'm right and there is a higher level of control — and indeed there has to be — then this level ceases its activity at the moment of death.
Think first of a living dog, then of a decomposing corpse. At the moment of death, all the living processes normally studied by the biologist rapidly disintegrate. The corpse remains subject to the same laws of physics and chemistry as the live dog, but now, with the cessation of life, we see those laws strictly in their own terms, without anything the life scientist is distinctively concerned about. The dramatic change in his descriptive language as he moves between the living and the dead tells us just about everything we need to know. No biologist who had been speaking of the behavior of the living dog will now speak in the same way of the corpse’s “behavior.” Nor will he refer to certain physical changes in the corpse as reflexes, just as he will never mention the corpse’s responses to stimuli, or the functions of its organs, or the processes of development being undergone by the decomposing tissues. Virtually the same collection of molecules exists in the canine cells during the moments immediately before and after death. But after the fateful transition no one will any longer think of genes as being regulated, nor will anyone refer to normal or proper chromosome functioning. No molecules will be said to guide other molecules to specific targets, and no molecules will be carrying signals, which is just as well because there will be no structures recognizing signals. Code, information, and communication, in their biological sense, will have disappeared from the scientist’s vocabulary. The corpse will not produce errors in chromosome replication or in any other processes, and neither will it attempt error correction or the repair of damaged parts. More generally, the ideas of injury and healing will be absent. Molecules will not recruit other molecules in order to achieve particular tasks. No structures will inherit features from parent structures in the way that daughter cells inherit traits or tendencies from their parents, and no one will cite the plasticity or context-dependence of the corpse’s adaptation to its environment. (...) The mystery in all this does not lie primarily in isolated “mechanisms” of interaction; the question, rather, is why things don’t fall completely apart — as they do, in fact, at the moment of death. What power holds off that moment — precisely for a lifetime, and not a moment longer? [Stephen L. Talbott]
Box_{November 18, 2015
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Well, then we're just left with your bald claim.Zachriel_{November 18, 2015
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Zach #63: You quote me saying:
My claim is that the astounding level of cooperation between millions of individual DNA strings that we see in a multicellular organism, which is beyond any comparison — the amazing coordination of a flock of birds included —, must have an explanation that includes a level of control over and above the millions of individual DNA strings.
Here I meant to say that the "astounding level of cooperation between millions of individual DNA strings that we see in a multicellular organism" cannot be compared with anything — "beyond any comparison". "The amazing coordination of a flock of birds included" means that a flock of birds also fails as an apt comparison.Box_{November 18, 2015
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Zachriel: You are claiming that global structures can’t occur due to local non-guided interactions. That is not correct. A flock forms due to the interaction between neighboring birds without regard to any global pattern. Box: My claim is that the astounding level of cooperation between millions of individual DNA strings that we see in a multicellular organism, which is beyond any comparison — the amazing coordination of a flock of birds included —, must have an explanation that includes a level of control over and above the millions of individual DNA strings. Please note that you were responding to the example we provided concerning flocking behavior.Zachriel_{November 18, 2015
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Zach: You claimed that “the amazing coordination of a flock of birds” must have a level of control over and above the actions of the individual birds.
Can you point out where I made this claim? To my knowledge I did not make that claim.Box_{November 18, 2015
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Box: Simple indeed. You claimed that "the amazing coordination of a flock of birds" must have a level of control over and above the actions of the individual birds. However, we know that global patterns can emerge from very simple rules, including flock behavior.Zachriel_{November 18, 2015
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Zach:
Box: My claim is that the astounding level of cooperation between millions of individual DNA strings that we see in a multicellular organism, which is beyond any comparison — the amazing coordination of a flock of birds included —, must have an explanation that includes a level of control over and above the millions of individual DNA strings.
A flock of birds, a school of fish, a swarm of insects, all form from a few simple rules. Basically, individuals just keep a certain distance between themselves and their neighbors. It’s an emergent behavior that does not require any central coordination. It’s simple to simulate.
Simple indeed. Too simple! You point out that all the birds do the same thing: they “just keep a certain distance between themselves and their neighbors.” But that is exactly the reason why your comparison isn’t apt. You might have had a point if a flock of birds started to morph into different parts and self-organized into an airplane. Although such a phenomenon would immediately raise questions: how do the birds know which parts they should form and what directs the different parts to their unique locations? In other words, what is the higher level of control?Box_{November 18, 2015
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A flock of birds, a school of fish, a swarm of insects, all form from a few simple rules.
The rules of design.Virgil Cain_{November 18, 2015
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Box: My claim is not simply that “global structures can’t occur due to local non-guided interactions”. The sun has a global structure which arguably arises due to local non-guided interactions. You said, "The concept of millions of ‘master-controllers’ that operate independently from each other is simply incoherent." The Sun is made up of millions of individual particles operating independently from each other that control the global structure. Box: My claim is that the astounding level of cooperation between millions of individual DNA strings that we see in a multicellular organism, which is beyond any comparison — the amazing coordination of a flock of birds included —, must have an explanation that includes a level of control over and above the millions of individual DNA strings. A flock of birds, a school of fish, a swarm of insects, all form from a few simple rules. Basically, individuals just keep a certain distance between themselves and their neighbors. It's an emergent behavior that does not require any central coordination. It's simple to simulate. By the way, the use of adjectives, such as 'astonishing', doesn't imply incoherence.Zachriel_{November 18, 2015
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Zach: You are claiming that global structures can’t occur due to local non-guided interactions. That is not correct. A flock forms due to the interaction between neighboring birds without regard to any global pattern.
My claim is not simply that “global structures can’t occur due to local non-guided interactions”. The sun has a global structure which arguably arises due to local non-guided interactions. My claim is that the astounding level of cooperation between millions of individual DNA strings that we see in a multicellular organism, which is beyond any comparison — the amazing coordination of a flock of birds included —, must have an explanation that includes a level of control over and above the millions of individual DNA strings. You link to a Wiki page, but it doesn’t offer a coherent concept of a bottom-up explanation. It points out that particular proteins and mRNAs are involved in embryogenesis but that doesn’t begin to explain how they can conceivably direct a process which inevitably requires a higher level of control and overview. In the article is a link to cell-cell communication in plants embryogenesis, but such communications are “horizontal” and therefore don’t explain what needs to be explained. Again, what is needed for things to make sense are coherent clear “indisputable” instructions for millions of individual DNA strings from a higher level.Box_{November 18, 2015
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Box: are you arguing that a multi-cellular organism can be “explained” by millions of cells who operate independently from each other? You are claiming that global structures can't occur due to local non-guided interactions. That is not correct. A flock forms due to the interaction between neighboring birds without regard to any global pattern. During embryogenesis, each cell gives and receives messages from neighboring cells, and keeps a record of its own proliferation. Scientists have manipulated this process in order to understand its workings. The process is very similar for most of metazoa. https://en.wikipedia.org/wiki/Cell_fate_determination Box: This teamwork of millions of individual DNA strings in a multicellular organism is inconceivable absent a level of control over and above the individual DNA strings. https://www.youtube.com/watch?v=Z3sLhnDJJn0Zachriel_{November 18, 2015
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// Rephrasing my argument against naturalistic gene-centric biology, which I argued in #44 and #46: - - - (1) Multicellular organisms, consisting of millions of individual DNA strings which work as a team, exist. (2) This teamwork of millions of individual DNA strings in a multicellular organism is inconceivable absent a level of control over and above the individual DNA strings. (3) Naturalistic gene-centric biology denies the existence of a level of control over and above the individual DNA string. Conclusion: naturalistic gene-centric biology cannot explain multicellular organisms, as defined in (1).Box_{November 18, 2015
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DTZ @ 53 Please, calm down. Are you sure you know well what you're commenting on? I respect your opinion, but that's just an opinion. What you wrote @52 is also off target.Dionisio_{November 18, 2015
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Dionisio Regarding your comment No. 51 Shame on you! Your comment is not true. You should learn to be more respectful of others.DTZ_{November 17, 2015
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Jack Jones Regarding your comment No. 48, may I disagree? Professor Moran has been respectful but I don't think Dionisio has been respectful. Clearly his comments are intended to discredit the professor, maybe because he disagrees with the professor's position. That's unfair, isn't it? Did you read Dionisio's strange questions? They are not clear, very confusing. Not the standard questions we should expect in a forum like this. Obviously made with the intention to bother and mortify. Why do they allow that kind of behaviour in this site? Maybe because Dionisio is one of the ID proponents he can get away with it? Is that why he is allowed to mistreat the professor publicly?DTZ_{November 17, 2015
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Jack Jones @48 Yes, I see what you mean. Perhaps the professor is not aware of the poor impression his attitude and behavior have left in a public forum like this, where so many anonymous lurkers read the posted comments and draw their own conclusions accordingly. I think my questions were simple, straightforward, easy to respond honestly. However, some of them reveal motives. Sometimes people don't like to expose their motives. Given his alleged academic credentials and scientific experience, I thought the professor would provide links to interesting research papers and/or bring to our discussion very knowledgeable specialists in the discussed topics. Maybe still it's possible the professor will reconsider his decision and come back to discuss seriously?Dionisio_{November 17, 2015
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Zach, are you arguing that a multi-cellular organism can be "explained" by millions of cells who operate independently from each other? Let's be clear on this. Is that what you are you saying?Box_{November 17, 2015
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Box: The alternative “all agents at the plant work completely independent from each other — each of them decides on its own what to do — but somehow things fall together perfectly every time” fails to make sense. That can occur when everyone's success depends on the success of the whole, even though there is no master control. It can happen even when no one is aware of the overall global structure, such as the "invisible hand" of the market.Zachriel_{November 17, 2015
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@43"Are you quitting because you’ve found my simple questions difficult for you to handle? Why? They couldn’t be easier." It could be because you exposed him, When I exposed Moran on his Blog then he started deleting my responses to him. It also could be because he does not know. Larry Moran does not even know whether the evolution that he believes in, occurs according to need or irregardless of need. He is talking respectfully to some people here but then he will use the term IDiots on his blog. He is two faced and infantile for an academic and does not deserve any respect. I was respectful to him but he did not want to reciprocate, You have been respectful and see how he has ended up responding to you.Jack Jones_{November 17, 2015
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Professor Moran, Thank you for your comments. I understand your point that it is unreasonable to ask for an explanation of a particular event when that event is governed by a probabilistic law. One does not ask why a radioactive decay event occurred here and now, for instance. Nevertheless, I would argue highly anomalous events require an explanation of some sort (e.g an exceptionally large or small genome size), as well as patterns which appear in certain classes of events (e.g. salamanders in general have very large genomes). I found out, by looking up the genome sizes of various fish species, that the genome of the pufferfish, while small, is not exceptionally so. I've also found out that organisms with small genomes tend to lose nongenic DNA very quickly, while organisms with large genomes tend to lose this kind of DNA very slowly. I also checked out what you wrote about effective population sizes, and it turns out that pufferfish have an effective population size of 10^5, which is quite large for a vertebrate (cf. 10^4 in humans). I'm afraid haven't been so lucky with onions: I haven't found any evidence of small populations and slow reproduction rates, which could explain their large genomes. Polyploidy doesn't apply to them either, according to T. Ryan Gregory. Thanks for the information on DNA deletion experiments in mice.vjtorley_{November 17, 2015
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Zachriel:
Box: There has to be a center of control.
That’s your presupposition, not an argument.
The argument I provided is that "the concept of millions of ‘master-controllers’ that operate independently from each other is simply incoherent." I can easily provide an example: When we visit a car assembly plant and see how all sorts of disjoint parts, robots and craftsmen work in concert and reach a common goal, then we immediately understand that there has to be a center of control. The alternative "all agents at the plant work completely independent from each other — each of them decides on its own what to do — but somehow things fall together perfectly every time" fails to make sense.Box_{November 17, 2015
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Box: There has to be a center of control. That's your presupposition, not an argument.Zachriel_{November 17, 2015
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Larry Moran: Not it’s entirely possible that I could be wrong about epigenetics and it really does present a challenge for evolutionary theory.
More fundamentally it poses a challenge for any naturalistic bottom-up explanation of an organism. In order to provide such a bottom-up explanation naturalism requires a ‘master-controller’ at the level of the parts — and the sole candidate seems to be DNA. A ‘master-controller’ is by definition a “self-mover”, that is it controls itself. This is a highly debated concept in philosophy — with strong relations to the concept of freedom, responsibility, ‘causa sui’ and God. Yet the very concept of ‘self-control’ seems to lie at the heart of the naturalistic concept of an organism; projected in DNA. The naturalistic idea is that DNA controls the various factors that control DNA, so that, in effect, DNA controls itself. I have asked Larry Moran how that concept makes sense.
Larry Moran: Easy. Genes make transcription factors and other regulatory molecules and those molecules control gene expression.
Larry Moran doesn’t see any problem. The DNA-molecule directs itself “easy”.
Larry Moran: During development the timing is the key. First you make one set of transcription factors from one set of genes then they turn on a second set of genes that make new transcription factors that turn on a third set of genes etc. The initial stimulus is in the egg cell in animals and that, in turn, is due to timing during oogenesis.
A tightly regulated program is being executed like clockwork. This is the naturalistic concept of an organism. Apart from epigenetics there are more basic challenges for this view, for instance: The multi-cellular organism
Larry Moran: In more complex organisms, development and differentiation is determined by the timing of differential gene expression during embryogenesis. We have very well understood examples of how this works in fruit flies and nematodes and lots of evidence to show that the same processes operate in humans and mice. The whole pathway is determined by transcription factors and other regulatory molecules that are deposited in the gametes during their formation. Again, we have the data, we know the molecules, we understand the process and the timing. There are no major mysteries.
//In post #22 I quote S.Meyer who points at "membrane targets" during the embryogenesis of fruitflies*, which are arguably independent from DNA and therefore contradict Moran’s statements.// Returning to my more general note: especially during the main period of an organism’s development there simply has to be a higher level of an organization that directs DNA in the individual cells. The concept of millions of 'master-controllers' that operate independently from each other is simply incoherent. There has to be a center of control. Naturalism cannot ground such a single center of control and therefor it fails to explain an organism. This is my fundamental insight. Note that it is not enough for DNA in individual cells to “communicate” with each other. The problem that needs to be solved has organizational and authoritative aspects. // [* Frohnhöfer and Nüsslein-Volhard, “Organization of Anterior Pattern in the Drosophila Embryo by the Maternal Gene Bicoid”; Lehmann and Nüsslein-Volhard, “The Maternal Gene Nanos Has a Central Role in Posterior Pattern Formation of the Drosophila Embryo.” & Roth and Lynch, “Symmetry Breaking During Drosophila Oogenesis.”]Box_{November 17, 2015
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Larry Moran @38
I’m only going to engage people who ask honest questions and genuinely want to learn something or have a serious discussion.
Are you saying that the questions @23 & @24 are not honest? Why? Can you explain your opinion? Are you quitting because you've found my simple questions difficult for you to handle? Why? They couldn't be easier. Is this how you treat your students too? Is this how you relate to other people? Can you do better than this? BTW, regarding honesty and seriousness, please take a look at my comments @41 & @42. Sorry to see you giving up this early in our discussion. Please, reconsider your decision. Take a break, rest and then think about it again.Dionisio_{November 16, 2015
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Mapou @40 You may want to look at comment @41.Dionisio_{November 16, 2015
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Virgil Cain @39 Perhaps you misunderstood the term 'origins' in Professor Moran's comments? I think he's referring to DNA replication origins, not to OOL. But I could be wrong too. You may want to read the first few lines @4 in this thread to see what the word 'origins' mean in that case.Dionisio_{November 16, 2015
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Cain:
Also can you link to this alleged evolutionary theory so we can all see what it actually says so we can all see what actually challenges it?
Yeah. Let's see this theory, especially the all-important chapter on how to conduct experiments to falsify it. Never mind. I was just joking. I know I'm dealing with pseudoscientists, charlatans and impostors.Mapou_{November 16, 2015
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