Origins codes for DNA: Argument for design?

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

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

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

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

Well, then we're just left with your bald claim. Zachriel

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

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

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

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

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

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

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

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

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=Z3sLhnDJJn0 Zachriel

// 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

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

Dionisio Regarding your comment No. 51 Shame on you! Your comment is not true. You should learn to be more respectful of others. DTZ

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

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

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

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

@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

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

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

Box: There has to be a center of control. That's your presupposition, not an argument. Zachriel

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

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

Mapou @40 You may want to look at comment @41. Dionisio

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

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

Larry Moran:

We’ve known about origins of replication for almost 50 years.

What does that mean, Larry? Does it mean we knew it had an origin because we don't know how it originated, even to this very day. 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? One more thing- you still have no idea what determines an organism's final form. Your reference to Venter proves that you don't have a clue. Virgil Cain

Professor Moran, Would you mind answering the questions @23 & @24? Yes. I'm only going to engage people who ask honest questions and genuinely want to learn something or have a serious discussion. I'll ignore everyone else. That includes you. Still not sure about Box. Larry Moran

Professor Moran, Would you mind answering the questions @23 & @24? Thank you. Here's the link to post 23: https://uncommondesc.wpengine.com/design-inference/origins-codes-for-dna-argument-for-design/#comment-588266 Dionisio

gpuccio RE: posts #18, #25, #30 If one or both of the mentioned nonessential functional parts, subsystems or mechanisms (small TV screens and power outlet) get removed, would the airplane still be able to perform its main function - i.e. fly and transport people from a location to another? Are there equivalent situations in biology research? Dionisio

Box says,

Larry Moran seems to be in denial about the challenge for neo-darwinian (and neutral theory) evolution posed by epigenetics.

Really? Let's take methylation of DNA as one of the classic example of epigenetics. We've known about that for 40 years and I've been teaching it for almost as long. We know the enzymes and we know how they work. We know how the epigenetic marks are inherited. Epigenetics Restriction, Modification, and Epigenetics Not it's entirely possible that I could be wrong about epigenetics and it really does present a challenge for evolutionary theory. Maybe I just missed it sometime over the past four decades. However, quoting Stephen Meyer as your authority on this subject seems to violate some of the principles you adhere to; namely, demanding that your "expert" really is an expert. Larry Moran

Larry Moran, "Two large sections of the mouse genome were deleted..." Isn't this the study where some of the deleted DNA is highly conserved, yet they found no obvious deleterious effects to the mice. What would cause this DNA to be conserved? Is there some tool that unusually conserves DNA other than natural selection? bFast

2. I understand that fish in a closely related family have genomes that are twice the size of pufferfish. What happens when scientists remove the excess DNA from the genomes of some of these fish and breed them for a few generations? Has this experiment been attempted, and if so, were any deleterious effects observed in the population with pruned DNA? Just curious.

No, nobody has done those experiments and nobody is ever going to do them. The experiment is too difficult and expensive and there are better ways to determine if the excess DNA is junk or not.

3. I understand that similar experiments were performed in mice a few years ago. Casey Luskin has a report on it here: http://www.evolutionnews.org/2.....62001.html

Two large sections of the mouse genome were deleted in a small-scale attempt to see if any of the putative genes in those regions really were genes. The mice seemed to survive very well suggesting strongly that there not dozens of functional genes in those regions as some people were predicting. Larry Moran

Vincent Torley asks,

1. Do scientists have any idea yet why pufferfish have such small genomes, or why onions have such large ones? It strikes me that until we can answer these questions and make quantitative predictions about the size of an organism’s junk DNA, we can’t really be said to have a scientific theory of junk DNA.

No, we don't know why pufferfish have small genomes and we don't know why two closely related species of onion can have very different genome sizes. We don't have (or want) a scientific theory of junk DNA in the sense you imagine. We're talking about the history of life here and these are unique events. The very best we can do is to make sure that evolutionary theory isn't violated or refuted by the existence of species with lots of junk DNA in their genome. In other words, evolutionary theory has to be compatible with what we observe. The older version of evolutionary theory (Darwinism) was NOT compatible but the modern version that includes Neutral Theory, random genetic drift, and advanced population genetics IS compatible. The modern version of evolutionary theory would strongly suggest that species with large population sizes and rapid reproduction rates would not have much junk DNA in their genomes. I would also indicate that species with small populations and slow reproduction rates would probably have a junky genome. These are probabilities. That's how biology works. Within the range of probably outcomes there are always going to be species in the tails of the probability distribution. You can't predict which particular species will have a genome size of "x." Think of it this way. The laws and theories of physics are very robust and well-confirmed. Yet they cannot predict how many planets we will find around a given main sequence star. Surely you don't think that's a flaw in the theories, do you? Or try this. Our understanding of what causes cancer is getting quite sophisticated. But we'll never be able to predict whether a given person will get bladder cancer or not. The best we can do is assign probabilities. We won't throw out our understanding of cancer if the person dies of a heart attack when they are 110 years old or if they die of leukemia when they are a child. You are asking for the impossible when you demand a theory that makes "quantitative predictions about the size of an organism’s junk DNA." I'm surprised you don't know this since you are an intelligent design proponent. Or am I missing something? Does ID make such quantitative predictions about junk DNA? Larry Moran

Hi Professor Moran, Thank you for your response. You wrote:

Why couldn’t our genome be one-tenth the size it is now in which case there would only be 10 mutations per generation? (The number of mutations per generation depends on the amount of DNA that’s being replicated.) This is what we see in pufferfish where a much smaller genome seems to work just fine. This is where the Onion Test becomes useful. Does your speculation pass the Onion Test?

I'd like to ask you a couple of questions. 1. Do scientists have any idea yet why pufferfish have such small genomes, or why onions have such large ones? It strikes me that until we can answer these questions and make quantitative predictions about the size of an organism's junk DNA, we can't really be said to have a scientific theory of junk DNA. 2. I understand that fish in a closely related family have genomes that are twice the size of pufferfish. What happens when scientists remove the excess DNA from the genomes of some of these fish and breed them for a few generations? Has this experiment been attempted, and if so, were any deleterious effects observed in the population with pruned DNA? Just curious. 3. I understand that similar experiments were performed in mice a few years ago. Casey Luskin has a report on it here: http://www.evolutionnews.org/2012/07/new_scientist_c062001.html Are there any comments you'd like to make on his piece? Thank you. vjtorley

gpuccio @25

I would add redundancy to the model [...] both attain the same result, in different ways.

Yes, agree. Good catch! Thank you for adding it. I missed that important part, which is seen in some well designed complex models, like in large passenger airplanes or computer servers for banking systems. BTW, sometimes I've noticed in some biology research papers, that their experiments intentionally altered something within the observed system, apparently expecting to see a particular behavior change, but were surprised to discover that the affected system still managed to 'survive' or get away with the introduced 'alteration'. Then sometimes the given conclusion referred to some kind of unexpected redundancy. Did I understand that correctly? Dionisio

Larry Moran @20

Then my daughter (Ph.D. in astrophysics) explains to me that they already new that;

Huh?! :) Dionisio

Larry Moran @20

I’m certain that you are an expert on something.

Well, sorry to disappoint you, but I'm not an expert on anything, not even on my own ignorance. BTW, I suffer an incurable natural human malady that makes me resistant to admit my ignorance. Dionisio

gpuccio @25

What is certainly “functional”, but not essential, and probably not even desirable, is the self-assurance of those who, considering themselves experts (and being indeed experts), think that they can impose their views by authority and maybe arrogance, instead than by honest and patient and respectful intellectual confrontation, however non essential it may be.

Eccellente!!! Mile grazie mio caro amico Dottore! Dionisio

Larry Moran seems to be in denial about the challenge for neo-darwinian (and neutral theory) evolution posed by epigenetics. On the Sandwalk blog, march 2014, Larry writes:

Larry Moran: We're only going to cover epigenetics for a few minutes in today's class because there aren't any serious arguments in favor of changing our view of evolution because of epigenetics. However, we are going to spend a lot more time learning that evo-devo is just as stupid because there are some seriously misled developmental biologists who think that discoveries in their field change how we should view evolution. :-)

That would be the day!

NEO-DARWINISM AND THE CHALLENGE OF EPIGENETIC INFORMATION These different sources of epigenetic information in embryonic cells pose an enormous challenge to the sufficiency of the neo-Darwinian mechanism. According to neo-Darwinism, new information, form, and structure arise from natural selection acting on random mutations arising at a very low level within the biological hierarchy—within the genetic text. Yet both body-plan formation during embryological development and major morphological innovation during the history of life depend upon a specificity of arrangement at a much higher level of the organizational hierarchy, a level that DNA alone does not determine. If DNA isn’t wholly responsible for the way an embryo develops—for body-plan morphogenesis—then DNA sequences can mutate indefinitely and still not produce a new body plan, regardless of the amount of time and the number of mutational trials available to the evolutionary process. Genetic mutations are simply the wrong tool for the job at hand. Even in a best-case scenario—one that ignores the immense improbability of generating new genes by mutation and selection—mutations in DNA sequence would merely produce new genetic information. But building a new body plan requires more than just genetic information. It requires both genetic and epigenetic information—information by definition that is not stored in DNA and thus cannot be generated by mutations to the DNA. It follows that the mechanism of natural selection acting on random mutations in DNA cannot by itself generate novel body plans, such as those that first arose in the Cambrian explosion. [Stephen Meyer, ch.19, 'Darwin's Doubt']

It's pretty obvious why Larry is in denial mode: epigenetics spells disaster for his position.

Gpuccio #1: I don’t know what to say, but if I were a sincere neo darwinist, the emerging landscape of epigenetic control would probably encourage me to consider (intellectual) suicide. We have been saying many times, during the last few years, that the emerging complexity revealed by daily biological research is probably the strongest, ongoing argument for design. That is absolutely true. But I must say that the emerging functional complexity of the epigenetic landscape is really beyond all my most optimistic expectations!

Box

Dionisio @18: Yes, your example is fine. I would add redundancy to the model: maybe your wife looks at movies in the small video, and maybe you can look at movies on your laptop. You both attain the same result, in different ways. Larry Moran adds that "This blog would be an even better example". I can agree. Knowledge and intellectual confrontation are probably not essential. From some point of view. More essential from others. What is certainly "functional", but not essential, and probably not even desirable, is the self-assurance of those who, considering themselves experts (and being indeed experts), think that they can impose their views by authority and maybe arrogance, instead than by honest and patient and respectful intellectual confrontation, however non essential it may be. gpuccio

Larry Moran @20

Sharing “vast knowledge” with you is just going to be a waste of time.

Professor Moran, Apparently you started our chatting in this UD blog last October, didn't you? Can you explain what motivated you to write to me first? Here's a quick hint: https://uncommondesc.wpengine.com/intelligent-design/are-some-of-our-opponents-in-the-grip-of-a-domineering-parasitical-ideology/#comment-587914 BTW, I assume you don't have to consult your academic colleagues in order to prepare for answering the above question, do you? :) Dionisio

Larry Moran @20

That’s an incorrect statement, verging on a lie.

Is yours a scientific statement? Dionisio

Larry Moran is old-school and still believes that organisms are little machines that are controlled by DNA and the environment. He tries to keep up and claims to have read ‘Darwin’s Doubt’, but he obviously skipped over the part on epigenetics. The days that DNA ran the show are long gone Larry ….

DNA helps direct protein synthesis. Parts of the DNA molecule also help to regulate the timing and expression of genetic information and the synthesis of various proteins within cells. Yet once proteins are synthesized, they must be arranged into higher-level systems of proteins and structures. Genes and proteins are made from simple building blocks—nucleotide bases and amino acids, respectively—arranged in specific ways. Similarly, distinctive cell types are made of, among other things, systems of specialized proteins. Organs are made of specialized arrangements of cell types and tissues. And body plans comprise specific arrangements of specialized organs. Yet the properties of individual proteins do not fully determine the organization of these higher-level structures and patterns.12 Other sources of information must help arrange individual proteins into systems of proteins, systems of proteins into distinctive cell types, cell types into tissues, and different tissues into organs. And different organs and tissues must be arranged to form body plans. The hierarchical layering or arrangement of different sources of information. Note that the information necessary to build the lower-level electronic components does not determine the arrangement of those components on the circuit board or the arrangement of the circuit board and the other parts necessary to make a computer. That requires additional informational inputs. Two analogies may help clarify the point. At a construction site, builders will make use of many materials: lumber, wires, nails, drywall, piping, and windows. Yet building materials do not determine the floor plan of the house or the arrangement of houses in a neighborhood. Similarly, electronic circuits are composed of many components, such as resistors, capacitors, and transistors. But such lower-level components do not determine their own arrangement in an integrated circuit (see Fig. 14.2). In a similar way, DNA does not by itself direct how individual proteins are assembled into these larger systems or structures—cell types, tissues, organs, and body plans—during animal development.13 Instead, the three-dimensional structure or spatial architecture of embryonic cells plays important roles in determining body-plan formation during embryogenesis. Developmental biologists have identified several sources of epigenetic information in these cells. CYTOSKELETAL ARRAYS Eukaryotic cells have internal skeletons to give them shape and stability. These “cytoskeletons” are made of several different kinds of filaments including those called the “microtubules.” The structure and location of the microtubules in the cytoskeleton influence the patterning and development of embryos. Microtubule “arrays” within embryonic cells help to distribute essential proteins used during development to specific locations in these cells. Once delivered, these proteins perform functions critical to development, but they can only do so if they are delivered to their correct locations with the help of preexisting, precisely structured microtubule or cytoskeletal arrays (see Fig. 14.3). Thus, the precise arrangement of microtubules in the cytoskeleton constitutes a form of critical structural information. These microtubule arrays are made of proteins called tubulin, which are gene products. Nevertheless, like bricks that can be used to assemble many different structures, the tubulin proteins in the cell’s microtubules are identical to one another. Thus, neither the tubulin subunits, nor the genes that produce them, account for the differences in the shape of the microtubule arrays that distinguish different kinds of embryos and developmental pathways. Instead, the structure of the microtubule array itself is, once again, determined by the location and arrangement of its subunits, not the properties of the subunits themselves. Jonathan Wells explains it this way: “What matters in [embryological] development is the shape and location of microtubule arrays, and the shape and location of a microtubule array is not determined by its units.”14 For this reason, as University of Colorado cell biologist Franklin Harold notes, it is impossible to predict the structure of the cytoskeleton of the cell from the characteristics of the protein constituents that form that structure.15 Another cell structure influences the arrangement of the microtubule arrays and thus the precise structures they form and the functions they perform. In an animal cell, that structure is called the centrosome (literally, “central body”), a microscopic organelle that sits next to the nucleus between cell divisions in an undividing cell. Emanating from the centrosome is the microtubule array that gives a cell its three-dimensional shape and provides internal tracks for the directed transport of organelles and essential molecules to and from the nucleus.16 During cell division the centrosome duplicates itself. The two centrosomes form the poles of the cell-division apparatus, and each daughter cell inherits one of the centrosomes; yet the centrosome contains no DNA.17 Though centrosomes are made of proteins—gene products—the centrosome structure is not determined by genes alone. MEMBRANE PATTERNS 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. Ion Channels and Electromagnetic Fields Membrane patterns can also provide epigenetic information by the precise arrangement of ion channels—openings in the cell wall through which charged electrical particles pass in both directions. For example, one type of channel uses a pump powered by the energy-rich molecule ATP to transport three sodium ions out of the cell for every two potassium ions that enter the cell. Since both ions have a charge of plus one (Na+, K+), the net difference sets up an electromagnetic field across the cell membrane.21 Experiments have shown that electromagnetic fields have “morphogenetic” effects—in other words, effects that influence the form of a developing organism. In particular, some experiments have shown that the targeted disturbance of these electric fields disrupts normal development in ways that suggest the fields are controlling morphogenesis.22 Artificially applied electric fields can induce and guide cell migration. There is also evidence that direct current can affect gene expression, meaning internally generated electric fields can provide spatial coordinates that guide embryogenesis.23 Although the ion channels that generate the fields consist of proteins that may be encoded by DNA (just as microtubules consist of subunits encoded by DNA), their pattern in the membrane is not. Thus, in addition to the information in DNA that encodes morphogenetic proteins, the spatial arrangement and distribution of these ion channels influences the development of the animal. The Sugar Code Biologists know of an additional source of epigenetic information stored in the arrangement of sugar molecules on the exterior surface of the cell membrane. Sugars can be attached to the lipid molecules that make up the membrane itself (in which case they are called “glycolipids”), or they can be attached to the proteins embedded in the membrane (in which case they are called “glycoproteins”). Since simple sugars can be combined in many more ways than amino acids, which make up proteins, the resulting cell surface patterns can be enormously complex. As biologist Ronald Schnaar explains, “Each [sugar] building block can assume several different positions. It is as if an A could serve as four different letters, depending on whether it was standing upright, turned upside down, or laid on either of its sides. In fact, seven simple sugars can be rearranged to form hundreds of thousands of unique words, most of which have no more than five letters.”24 These sequence-specific information-rich structures influence the arrangement of different cell types during embryological development. Thus, some cell biologists now refer to the arrangements of sugar molecules as the “sugar code” and compare these sequences to the digitally encoded information stored in DNA.25 As biochemist Hans-Joachim Gabius notes, sugars provide a system with “high-density coding” that is “essential to allow cells to communicate efficiently and swiftly through complex surface interactions.”26 According to Gabius, “These [sugar] molecules surpass amino acids and nucleotides by far in information-storing capacity.”27 So the precisely arranged sugar molecules on the surface of cells clearly represent another source of information independent of that stored in DNA base sequences. [Stephen Meyer, ch. 14, ‘Darwin’s Doubt’].

Box

Dionisio asks,

Regarding your second item (b) in your commentary, would the following example qualify as a case of a designed object component or feature that is functional but not essential?

This blog would be an even better example. :-) Larry Moran

Dionisio says,

Facing so many interesting research papers we feel like children in a gigantic toy store.

I understand the feeling. I feel the same way when I read papers about astrophysics. Then my daughter (Ph.D. in astrophysics) explains to me that they already new that; it's wrong; or it's just an incremental addition to what they already know. Those are pretty much my reactions when I read about "exciting" new discoveries in biochemistry, molecular biology, and evolution. It a rare day when I read something new that has to go into my textbook. Dionisio, I'm certain that you are an expert on something. When you read popular press reports about new and exciting discoveries in your field do you feel like a child in a candy store or do you recognize that the popular press exaggerates a little bit?

As researchers dig deeper into more accurate levels of details, they discover more purpose-driven specified functional prescriptive information being transmitted and interpreted within the biological systems.

That's an incorrect statement, verging on a lie. "Researchers" are NOT discovering "purpose-driven specified functional prescriptive information." Just the opposite. Researchers in general are still convinced that there's no evidence of purpose in biochemistry and molecular biology. What you may be seeing is propaganda from Intelligent Design Creationists who are interpreting the data according to their preconceptions of what it should be demonstrating. Lawyer Barry Arrington will explain to you why their logic is faulty and their assumptions are incorrect. BTW, I can see now that you probably weren't telling the truth when you implied earlier that you had an open mind and just wanted to learn about developmental biology. Here's what you said a few days ago ...

When science is discussed seriously, we all benefit. In this case, given the highly disproportionate knowledge difference between a science professor and a nobody like me, the biggest beneficiary is the ignorant who can learn much from the friendly exchange of information, which is mostly a one-way flow. Again, thank you for your willingness to share your vast knowledge with me and other interested readers.

Here's what you said today.

Complex complexity. Indeed! The more we know, the more we have to learn. Unending Revelation of the Ultimate Reality.

Your mind is already made up. Sharing "vast knowledge" with you is just going to be a waste of time. Larry Moran

@10 Larry Moran "He and I disagree on a number of things. We’ve been arguing about them for almost twenty years. He continues to comment on Sandwalk from time to time. I’ve been to his house in Oxford to discuss our differences over molecular evolution. " Now I heard a rumor that I would like Professor Moran to confirm or deny if possible. I heard this rumor that when you went to Dawkins house, that you asked him where your cup of tea was and that Dawkins said that he was waiting for the tea to be made by chance for you. I heard that you got your own back though and when it came to the roast dinner then you started throwing the roast potatoes from your plate and when Dawkins said to you, what the hell are you doing Larry? Then you said, Richard, I am just testing the hypothesis that selecting something for elimination from my plate is going to create something that never was on my plate. Did this happen Professor? Jack Jones

gpuccio @16 Regarding your second item (b) in your commentary, would the following example qualify as a case of a designed object component or feature that is functional but not essential? The small TV screens that are attached to the back of the seats in the economy class of some airplanes are not essential, but definitely have a function. My wife sometimes watches films during our long flights. However, I rarely look at those screens, because I usually just read offline a few PDF documents I download before the flight. Another thing I consider very handy is the power outlet located right between our two seats, which allows me to charge my tablet during long flights. Though functional, that power outlet is not essential. If any of those two things (or both) were broken or removed, we still could get to our destination, assuming all the essential parts were in place and well. BTW, not sure if this is 'off topic' for this current thread, but wanted to let you know that for some reason your name came to my mind when I saw this: http://www.sciencedirect.com/science/journal/00145793/589/20/supp/PA Dionisio

Vincent Torley says,

Well, if we’re talking about all noncoding DNA, then Professor Moran is of course correct. But if we’re talking about most DNA, that’s another story entirely:

Thanks. Let's put a stop to this stupid myth about scientists thinking that since only 2% of our genome encodes protein therefore all the noncoding DNA (98%) is junk. It started out as a misconception (perhaps) but now it's a lie to repeat it.

But then I had a look at Dr. Richard Sternberg’s posts on LINEs and SINEs (see here, here and here), and I have to say I thought Dr. Sternberg made a good case for these segments being the product of design.

What you have to keep in mind is that the vast majority of SINES and LINES contain mutations that make them unable to transpose. In most cases, the signals consist of little more than bits and pieces of sequences that use to be intact SINCE and LINES. The total number of functional transposons in the genome accounts for less than 1%. About 50% of the genome consists of defective bits of transposons. That doesn't look like design to me. It looks like pseudogenes. I count the functional transposons as part of the functional fraction of the genome. Furthermore, it doesn't make sense to postulate that all the defective transposon fragments have secondarily acquired a function. There's suggestive evidence that a few of them might have a new function but even in order to arrive at a "few" you have to add together results from a dozen different species. Also, when you are thinking about this issue, remember that every newborn baby has about 100 new mutations. If most of our genome were functional then a huge number of these mutations are going to be detrimental and our species could not survive. It follows that most mutations have to be neutral which means that most of our genome has to nonfunctional junk DNA. This is the genetic load argument for junk DNA first advanced in the late 1960s.

Professor Moran, are you aware of any evidence that the genomes of organisms living 10 million, 100 million or 500 million years ago were smaller on average than they were today?

We talked about this when Carl was in Toronto last December preparing this article. Junk DNA comments in the New York Times Magazine I don't agree with Carl. I don't think there's any evidence that the immediate ancestors of humans had smaller genomes. However, it seems reasonable that once you get back 500 million years or so it's very likely that our ancestors had smaller genomes.

What I’m suggesting is that junk DNA could itself be a design feature, and that the percentage of junk DNA should be no higher than it needs to be, to ensure the long-term survival of the species.

This doesn't make sense. Why couldn't our genome be one-tenth the size it is now in which case there would only be 10 mutations per generation? (The number of mutations per generation depends on the amount of DNA that's being replicated.) This is what we see in pufferfish where a much smaller genome seems to work just fine. This is where the Onion Test becomes useful. Does your speculation pass the Onion Test? Larry Moran

VJ: Just a few thoughts: a) Transposons are certainly a powerful tool for the remolding of the genomes in the course of natural history. Whether such remolding is a random functionless process, or a guided one which designs function, or just the occasional object of random "exaptation" leading to function by mere luck, remains to be decided, and could be one of the important fileds of confrontation between ID and neo darwinism (in any of its forms). b) Saying that "every piece of the genome is essential" is not the same as saying that every piece, or most, of the genome is functional. Function is not the same thing as essentiality. We learn from design in general, and from biology in particular, that many functions can be redundant, and that a good design is often associated to "escape routes", to alternative ways of doing the same essential thing. Epigenetics is a wonderful example of many different levels interacting in flexible ways to realize highly efficient control. Therefore, a lot of the genome could be functional without being essential, and so the human species, as well as other species, can probably avoid becoming extinct in less than a century. gpuccio

Professor Moran writes:

There was never a time when knowledgeable scientists thought that all noncoding DNA was junk.

Well, if we're talking about all noncoding DNA, then Professor Moran is of course correct. But if we're talking about most DNA, that's another story entirely:

[T. Ryan] Gregory believes that while some noncoding DNA is essential, most probably does nothing for us at all, and until recently, most biologists agreed with him. Surveying the genome with the best tools at their disposal, they believed that only a small portion of noncoding DNA showed any evidence of having any function. But in the past few years, the tide has shifted within the field... In 1964, the German biologist Friedrich Vogel did a rough calculation of how many genes a typical human must carry... If the human genome was made of nothing but genes, Vogel found, it would need to have an awful lot of them — 6.7 million genes by his estimate, a number that, when he published it in Nature, he admitted was “disturbingly high.” Vogel speculated that a lot of the genome was made up of essential noncoding DNA — possibly operating as something like switches, for example, to turn genes on and off. But other scientists recognized that even this idea couldn’t make sense mathematically. On average, each baby is born with roughly 100 new mutations. If every piece of the genome were essential, then many of those mutations would lead to significant birth defects, with the defects only multiplying over the course of generations; in less than a century, the species would become extinct. Faced with this paradox, Crick and other scientists developed a new vision of the genome during the 1970s. Instead of being overwhelmingly packed with coding DNA, the genome was made up mostly of noncoding DNA. And, what’s more, most of that noncoding DNA was junk — that is, pieces of DNA that do nothing for us. (Is Most of Our DNA Garbage? by Carl Zimmer, New York Times, March 5, 2015. Bolding mine - VJT.)

While Professor Moran is here, I have a few questions for him. I'm still making up my mind about what proportion of the human genome is functional. Recently, I watched Professor P.Z. Myers' 2011 talk on junk DNA and I thought he'd made a pretty convincing case (but see here fro another perspective), especially regarding LINEs and SINEs. But then I had a look at Dr. Richard Sternberg's posts on LINEs and SINEs (see here, here and here), and I have to say I thought Dr. Sternberg made a good case for these segments being the product of design. Surprisingly, despite the fact that his posts were written five years ago, I haven't seen a refutation from the "unguided evolution" camp, yet. Do you have any comments, Professor Moran? I've had another thought about Carl Zimmer's article. Zimmer writes:

Over millions of years, the human genome has spontaneously gotten bigger, swelling with useless copies of genes and new transposable elements. Our ancestors tolerated all that extra baggage because it wasn’t actually all that heavy. It didn’t make them inordinately sick. Copying all that extra DNA didn’t require them to draw off energy required for other tasks. They couldn’t add an infinite amount of junk to the genome, but they could accept an awful lot. To subtract junk, meanwhile, would require swarms of proteins to chop out every single dead gene or transposable element — without chopping out an essential gene. A genome evolving away its junk would lose the race to sloppier genomes, which left more resources for fighting diseases or having children.

Professor Moran, are you aware of any evidence that the genomes of organisms living 10 million, 100 million or 500 million years ago were smaller on average than they were today? Finally, here's a thought for ID theorists to ponder. Zimmer's article argues that if every piece of the genome were essential, then the human species would become extinct in less than a century. On that logic, there must be some critical percentage P of junk DNA in the human genome that would allow the human species to continue over very long periods of time (say, a million years). What I'm suggesting is that junk DNA could itself be a design feature, and that the percentage of junk DNA should be no higher than it needs to be, to ensure the long-term survival of the species. Thoughts? vjtorley

Larry Moran @8

We’ve known about origins of replication for almost 50 years. I worked on them a little bit when I was a graduate student in 1968.

Since then, some outstanding questions have been answered, but new important questions have been raised. That's why we look forward, with growing anticipation, to reading future research papers that might shed more light on the elaborate cellular and molecular information-processing choreographies orchestrated within the biological systems. This is a fascinating time to look at the very interesting data coming out of biological research, which is increasingly revealing a marvelous complexity that is turning more complex with every discovery. Just look at gpuccio, an experienced medical doctor, who reacts with such a contagious enthusiasm at the latest publications of new biological discoveries. Here's a recent example: https://uncommondesc.wpengine.com/genomics/the-amazing-design-of-the-genome/#comment-588110 Facing so many interesting research papers we feel like children in a gigantic toy store. As researchers dig deeper into more accurate levels of details, they discover more purpose-driven specified functional prescriptive information being transmitted and interpreted within the biological systems. Complex complexity. Indeed! The more we know, the more we have to learn. Unending Revelation of the Ultimate Reality. Dionisio

Additional related papers referenced @1153-1160 here: https://uncommondesc.wpengine.com/intelligent-design/mystery-at-the-heart-of-life/#comment-587959 Dionisio

I’ve been to his house in Oxford to discuss our differences over molecular evolution. Did that come in a mug or a bottle? Mung

Granted then not a nimcompoop but not knowledgeable either. Andre

Andre asks, I take then that Richard Dawkins is not a knowledgeable scientist but quite possibly a nimcompoop? He's not a nimcompoop. He and I disagree on a number of things. We've been arguing about them for almost twenty years. He continues to comment on Sandwalk from time to time. I've been to his house in Oxford to discuss our differences over molecular evolution. We respect each other's position even though we each think the other person is wrong. Richard Dawkins Talks About the Human Genome Richard Dawkins' View of Random Genetic Drift Larry Moran

Prof Moran I take then that Richard Dawkins is not a knowledgeable scientist but quite possibly a nimcompoop? Andre

We've known about origins of replication for almost 50 years. I worked on them a little bit when I was a graduate student in 1968. They are included in the functional part of the genome [What's in Your Genome?]. In fact, they are some of the well-known functional noncoding DNA sequences that I use to refute claims about noncoding DNA equaling junk DNA. Those claims by ID proponents (and some scientists) are false. There was never a time when knowledgeable scientists thought that all noncoding DNA was junk. Note: UD is inserting stuff into my comment that sometimes screws up the formatting. It is adding 'rel="nofollow"' to URLS. It's not my fault. Larry Moran

The additional questions to be addressed in the bacterial systems include the following: What are the determinants of R-loop propensity? What regulates conversion of R-loops to replication origins? Would cSDR occur in other instances of increased R-loop prevalence, such as in mutants deficient in Rho (discussed above) or topoisomerase I [103]–[105]? When forks undergo polar arrest at Tus-bound Ter sites in absence of oncoming forks, how does the postulated DNA degradation occur proximal to Ter? And what are the roles for single-strand DNA exonucleases in replication?

Gowrishankar J (2015) End of the Beginning: Elongation and Termination Features of Alternative Modes of Chromosomal Replication Initiation in Bacteria. PLoS Genet 11(1): e1004909. doi:10.1371/journal.pgen.1004909 http://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1004909

Complex complexity. Work in progress... stay tuned. Dionisio

The major ideas proposed in this review, which need to be tested in future studies, are [1] that fork reversal reactions occur when opposing replisomes meet; [2] that replication origins for bacterial cSDR are widespread in the genome (although the firing potential of any single origin is small); [3] that replication fork progression in cSDR faces two separate obstacles, of conflicts with transcription and of arrest at Tus-bound Ter sites; [4] and that cSDR-like events may contribute to R-loop mediated genome damage in eukaryotes.

Gowrishankar J (2015) End of the Beginning: Elongation and Termination Features of Alternative Modes of Chromosomal Replication Initiation in Bacteria. PLoS Genet 11(1): e1004909. doi:10.1371/journal.pgen.1004909 http://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1004909

Complex complexity. Work in progress... stay tuned. Dionisio

Many features of chromosomal DNA replication are shared across the three kingdoms of life, including initiation from discrete origins, bidirectional fork progression, and termination by merger of opposing replication forks.

Gowrishankar J (2015) End of the Beginning: Elongation and Termination Features of Alternative Modes of Chromosomal Replication Initiation in Bacteria. PLoS Genet 11(1): e1004909. doi:10.1371/journal.pgen.1004909 http://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1004909

Complex complexity. Dionisio

Chromosome replication starts at specific sites known as origins, where initiator proteins bind and recruit replication machinery components. For organisms with multiple replication origins on a chromosome, the coordination of origin utilization is vital to ensure complete and accurate genome duplication. [...] a dormant replication origin can be activated and becomes essential for chromosome replication in the absence of the other active origins [...] [...] mechanisms exist for regulating utilization of the multiple origins. For archaea with multiple origins on the chromosome, the corresponding initiators may have similar mechanisms for the regulation of initiation. Apart from the usage of distinct initiator proteins, archaeal replication origins (including the dormant origins) in one cell share common MCM and GINS, and other unknown factors. These factors may interact with the distinct oriCs and Cdc6s with different efficiencies, thereby coordinating the firing or inactivation of distinct origins [...] [...] multiple origins acting as a group may also be regulated by these factors via the same mechanisms to ensure the coordination of DNA replication with cell growth. [...] activation of the dormant origin but not recombination-dependent initiation is responsible for genome replication [...] The reason for [...] growth discrepancy is unknown, but all of these results indicate that there might be substantial differences between H. volcanii and H. mediterranei, even though they belong to the same genus. [...] chromosome replication may generally require at least one replication origin. [...] replication initiation from multiple origins (including dormant ones) could be extensively regulated, [...]

Activation of a dormant replication origin is essential for Haloferax mediterranei lacking the primary origins Haibo Yang, Zhenfang Wu, Jingfang Liu, Xiaoqing Liu, Lei Wang, Shuangfeng Cai & Hua Xiang Nature Communications 6, Article number: 8321 doi:10.1038/ncomms9321 http://www.nature.com/ncomms/2015/150916/ncomms9321/full/ncomms9321.html

Complex complexity. Work in progress ... stay tuned. Dionisio

What a delightful present for the weekend. News posting such a highly interesting and important topic and then to make it much better, gpuccio starts the follow-up discussion with his always very insightful comments, loaded with juicy information. Thank you News and gpuccio! Dionisio

News: Mcm2, one of the key factors in replication initiation, is a very conserved molecule in eukaryotes: Human - saccharomices cerevisiae blast: Score: 778 bits(2010) Expect: 0.0 Identities: 416/864(48%) Positives: 557/864(64%) Gaps: 76/864(8%) Length of human protein: 904 AAs. Even more so in vertebrates: Human - Callorhinchus milii (shark) blast: Score: 1587 bits(4108 Expect: 0.0 Identities: 762/906(84%) Positives: 834/906(92%) Gaps: 22/906(2%) Length of human protein: 904 AAs. From Wikipedia:

The protein encoded by this gene is one of the highly conserved mini-chromosome maintenance proteins (MCM) that are involved in the initiation of eukaryotic genome replication. The hexameric protein complex formed by MCM proteins is a key component of the pre-replication complex (pre-RC) and may be involved in the formation of replication forks and in the recruitment of other DNA replication related proteins. This protein forms a complex with MCM4, 6, and 7, and has been shown to regulate the helicase activity of the complex. This protein is phosphorylated, and thus regulated by, protein kinases CDC2 and CDC7.

gpuccio

News: There is this, too: "High-resolution profiling of Drosophila replication start sites reveals a DNA shape and chromatin signature of metazoan origins." http://ac.els-cdn.com/S2211124715003617/1-s2.0-S2211124715003617-main.pdf?_tid=87ea07f8-8ab2-11e5-bdf7-00000aacb35e&acdnat=1447493689_efb2df1121ad8a5af3f2505cd1d2d7ec Abstract:

At every cell cycle, faithful inheritance of metazoan genomes requires the concerted activation of thousands of DNA replication origins. However, the genetic and chromatin features defining metazoan replication start sites remain largely unknown. Here, we delineate the origin repertoire of the Drosophila genome at high resolution. We address the role of origin-proximal G-quadruplexes and suggest that they transiently stall replication forks in vivo. We dissect the chromatin configuration of replication origins and identify a rich spatial organization of chromatin features at initiation sites. DNA shape and chromatin configurations, not strict sequence motifs, mark and predict origins in higher eukaryotes. We further examine the link between transcription and origin firing and reveal that modulation of origin activity across cell types is intimately linked to cell-type-specific transcriptional programs. Our study unravels conserved origin features and provides unique insights into the relationship among DNA topology, chromatin, transcription, and replication initiation across metazoa.

And this: "DNA replication origins." http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3783049/ Abstract:

The onset of genomic DNA synthesis requires precise interactions of specialized initiator proteins with DNA at sites where the replication machinery can be loaded. These sites, defined as replication origins, are found at a few unique locations in all of the prokaryotic chromosomes examined so far. However, replication origins are dispersed among tens of thousands of loci in metazoan chromosomes, thereby raising questions regarding the role of specific nucleotide sequences and chromatin environment in origin selection and the mechanisms used by initiators to recognize replication origins. Close examination of bacterial and archaeal replication origins reveals an array of DNA sequence motifs that position individual initiator protein molecules and promote initiator oligomerization on origin DNA. Conversely, the need for specific recognition sequences in eukaryotic replication origins is relaxed. In fact, the primary rule for origin selection appears to be flexibility, a feature that is modulated either by structural elements or by epigenetic mechanisms at least partly linked to the organization of the genome for gene expression.

And this: "The Dynamics of Eukaryotic Replication Initiation: Origin Specificity, Licensing, and Firing at the SingleMolecule Level" http://ac.els-cdn.com/S1097276515001823/1-s2.0-S1097276515001823-main.pdf?_tid=a64dded6-8ab2-11e5-9bcf-00000aacb35e&acdnat=1447493740_2cabef08e8f0445994bffdcb8d9f5b06 Abstract:

Eukaryotic replication initiation is highly regulated and dynamic. It begins with the origin recognition complex (ORC) binding DNA sites called origins of replication. ORC, together with Cdc6 and Cdt1, mediate pre-replicative complex (pre-RC) assembly by loading a double hexamer of Mcm2-7: the core of the replicative helicase. Here, we use single-molecule imaging to directly visualize Saccharomyces cerevisiae pre-RC assembly and replisome firing in real time. We show that ORC can locate and stably bind origins within large tracts of non-origin DNA and that Cdc6 drives ordered pre-RC assembly. We further show that the dynamics of the ORC-Cdc6 interaction dictate Mcm2-7 loading specificity and that Mcm2-7 double hexamers form preferentially at a native origin sequence. Finally, we demonstrate that single Mcm2-7 hexamers propagate bidirectionally, monotonically, and processively as constituents of active replisomes.

Fascinating subject. As Dionisus would say: "Complex complexity". Indeed! Two points are probably worth of special consideration: a) The epigenetic control of replication origins. As usual, complex and flexible. b) the rather amazing connection between DNA replication organization and transcription organization. I don't know what to say, but if I were a sincere neo darwinist, the emerging landscape of epigenetic control would probably encourage me to consider (intellectual) suicide. We have been saying many times, during the last few years, that the emerging complexity revealed by daily biological research is probably the strongest, ongoing argument for design. That is absolutely true. But I must say that the emerging functional complexity of the epigenetic landscape is really beyond all my most optimistic expectations! gpuccio