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Antibody affinity maturation as an engineering process (and other things)

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In Kairosfocus’ very good thread about functional complexity, I posted about antibody affinity maturation as an example of a very complex engineering process embedded in biological beings. Both Kairosfocus and Dionisio suggested that I could open a new thread to discuss the issue. When such good friends ask, I can only comply.  🙂

For lack of time, I will try to be very simple.

First of all, I paste here my original post (#6 in the original thread):

KF:

Thank you for the very good summary. Among many other certainly interesting discussions, we may tend to forget sometimes that functionally specified complex information is the central point in ID theory. You are very good at reminding that to all here.

I would like to suggest a very good example of multilevel functional complexity in biology, which is often overlooked. It is an old favourite of mine, the maturation of antibody affinity after the initial immunological response.

Dionisio has recently linked an article about a very recent paper. The paper is not free, but I invite all those interested to look at the figures and legends, which can be viewed here:

http://www.nature.com/nri/jour…..28_ft.html

The interesting point is that the whole process has been defined as “darwinian”, while it is the best known example of functional protein engineering embedded in a complex biological system.

In brief, the specific B cells which respond to the epitope (antigen) at the beginning of the process undergo a sequence of targeted mutations and specific selection, so that new cells with more efficient antibody DNA sequences can be selected and become memory cells or plasma cells.

The whole process takes place in the Germinative Center of lymph nodes, and involves (at least):

1) Specific B cells with a BCR (B cell receptor) which reacts to the external epitope.

2) Specific T helper cells

3) Antigen presenting cells (Follicular dendritic cell) which retain the original epitope (the external information) during the whole process, for specific intelligent selection of the results

4) Specific, controlled somatic hypermutation of the Variable region of the Ig genes, implemented by the following molecules (at least):

a) Activation-Induced (Cytidine) Deaminase (AID): a cytosine:guanine pair is directly mutated to a uracil:guanine mismatch.

b) DNA mismatch repair proteins: the uracil bases are removed by the repair enzyme, uracil-DNA glycosylase.

c) Error-prone DNA polymerases: they fill in the gap and create mutations.

5) The mutated clones are then “measured” by interaction with the epitope presented by the Follicular DC. The process is probably repeated in multiple steps, although it could also happen in one step.

6) New clones with reduced or lost affinity are directed to apoptosis.

7) New clones with higher affinity are selected and sustained by specific T helper cells.

In a few weeks, the process yields high affinity antibody producing B cells, in the form of plasma cells and memory cells.

You have it all here: molecular complexity, high control, multiple cellular interactions, irreducible complexity in tons, spacial and temporal organization, extremely efficient engineering. The process is so delicate that errors in it are probably the cause of many human lymphomas.

Now, that’s absolute evidence for Intelligent Design, if ever I saw it. :)

The most interesting answers came from Aurelio Smith and sparc. I have already answered AS’s comment in the original thread. Spark’s comments were more specific, so I paste them here  (#58 and 59):

You haven’t looked up evolution of AID, did you?

and

BTW, you let out the part of the B-cell development that occurs without any antigen. Lots of mutations, rearragements and selection. Where and how does ID interfere in these processes. Especially, in cases of man made synthetic artificial antigens that were not present 50 years ago?

OK, I will make just a couple of comments on these two points here, and let the rest to the discussion:

a) My point was not specifically about the evolution of the individual proteins in the system, but about the amazing complexity of the whole system. So, I have not done any detailed analysis of the individual proteins I quote. However, I will look at that aspect. As sparc seems aware of specific information about the evolution of AID, I invite him ot provide some references, and we can certainly go on from there.

b) I did not “let out” the part of the B-cell development. I simply focused on affinity maturation. However, the part sparc alludes to is extremely interesting too, so I will mention here in very general lines how it works, and why it is another wonderful example of intelligent engineering. And we can obviously discuss this second aspect too.

In brief, the adaptive immune system must solve the problem of reacting t a great number of potential antigens/epitope, which are not known in advance (I will use “epitope” from now on, because that is the immulogically active part of an antigen).

So, the two branches of the adaptive immune system (B system and T system) must be “prepared” to recognized possible epitopes coming from the outer world. They do that by a “sensor” which is the B cel receptor (BCR) in the B system, and the T cell receptor (TCR) in the T system.

Let’s focus the discussion on the B system.

To recognize the greatest number of possible epitopes (IOWs, of possible small biochemical configurations, mainly of proteins but also of other molecules), the B immune system builds what is usually known as the “basic repertoire”.Very simply, B cells underso a process of somatic genetic differentiation, essentially based on the recombination of VDJ genes, which generates a basic repertoire of different B clones with specific variable genes for the heavy and light chain, IOWs a specific BCR. In that sense, immune cells are different from other somatic cells, because they have a specific genetic recombination of the variable chains of the BCR (and therefore of the antibody that they will produce.

No one knows exactly how big that repertoire is in each individual, but new techniques are helping much in studying it quantitatively. From what I have read, I would say that the size is probably somewhere between 10^6 and 10^9 (more or less the total number of B cells in an organism).

Now, what is the purpose of this basic BCR (antibody) repertoire? We can consider it as a “network” of lower affinity antibodies covering in a loose way the space of possible epitope configurations. That repertoire is generated blindly (IOWs, without any information about specific antigens) by a process of sophisticated genetic engineering (VDJ recombination and other factors), which again uses random variation in a controlled way to generate diversity.

So, to sum up. two different complex algorithms act to ensure efficient immune responses.

1) The first one generates a “blind” repertoire of lower affinity antibodies covering as well as possible the whole space of configurations of possible epitopes.

2) The second one (affinity maturation) refines the affinity of the B cells selected in the primary response (from the basic repertoire) so that they become high affinity, specialized memory cells. This is the process I described in the beginning, in my post.

Both processes are wonderful examples of sophisticated engineering and irreducibly complex systems, and they are completely different one from the other. Both processes work together in sequence in a sophisticated and irreducibly complex meta-system.

Both use controlled random variation to generate diversity. The second process also uses intelligent selection based on existing information from the environment (the epitope conserved in the Follicular GC cell).

All that is very brief, and in no way covers the whole complexity of what is known. So, let’s open the discussion.

Comments
Zachriel: Just a question. Why "we"? Are you a team? Or is it just plurale maiestatis? :)gpuccio
February 21, 2015
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Box: Well, contrary to what you claim in #510, a list of complex processes is no evidence whatsoever for an evolutionary history. A list is not evidence. Observations are evidence. See Abedin & King, Diverse evolutionary paths to cell adhesion, Trends in Cellular Biology 2010; or Miller et al., The evolutionary origin of epithelial cell-cell adhesion mechanisms, Current Topics in Membranes 2013. Box: Further I expect that there is no agreement between Gpuccio and you that there is any evidence for an evolutionary history. gpuccio: there is no doubt that an historical pattern exists. While gpuccio didn't indicate an evolutionary history, he clearly stated that an historical pattern exists. Gpuccio pointed to large gaps. We pointed out that the gaps are not as large as gpuccio suggests.Zachriel
February 21, 2015
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Zachriel,
Zachriel: evolutionary.
I thought so. Well, contrary to what you claim in #510, a list of complex processes is no evidence whatsoever for an evolutionary history. Just like a list of complex processes wrt a functional computer is no evidence whatsoever for an evolutionary history. Further I expect that there is no agreement between Gpuccio and you that there is any evidence for an evolutionary history.Box
February 21, 2015
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Box: What was an historical process The origin of the various processes that distinguish metazoans; e.g. adhesion, differentiation, apoptosis; as well as their diversification. Box: – and what kind? Evolutionary.Zachriel
February 21, 2015
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Zachriel,
Box: What exactly do you think that you and GPuccio agree on?
Zachriel: The reasonable list of complex processes; adhesion, differentiation, apoptosis; in other words, it was an historical process.
What was an historical process - and what kind? In a functional computer we can also distinguish between several complex processes. What kind of historical process does that imply?Box
February 21, 2015
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eccellente!!! Mile grazie mio caro Dottore!Dionisio
February 21, 2015
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Dionisio: You probably know many of my ideas well, but I will try to briefly sum up some definitions and concepts to answer the questions in your post #521: a) Design: any process where a conscious intelligent being purposefully outputs a specific form to a material object from a conscious representation of that form. b) We can know that an object is designed in two different ways: 1) Directly: we have direct observation, or some equivalent evidence, of the process in which the object acquires its form, and therefore we know that a conscious agent outputted intentionally that form into the object. That's the case with many human artifacts. 2) By inference. If no direct evidence of the process of origin is available, the best design inference can be made by the observation in the object of the property of CSI or some equivalent concept, which is empirically a very reliable marker of design. c) The I and D in ID are in reality connected. Design is by definition "intelligent", in the sense that the designer must have some cognitive representation to design. And it is also purposeful, because the designer must have a motivation to design. So, IMO, the word "design" would be enough. But I suppose that "intelligent" adds some protection from possible attempts at defining forms of "non designed design", like it has been done with "non free free will", and so on. I suppose that "conscious cognitive and purposeful design" would be too long! :) d) I don't believe there is any "third way". Nor that there are really two ways as defined in that thread, because Creationism, IMO, is not really a scientific position (although it is a perfectly acceptable philosophic and religious position). As far as I understand, neo darwinism (RV + NS) and ID are the only games in town, for a scientific debate about the origins of biological information. All the rest is bafflegab.gpuccio
February 21, 2015
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gpuccio Agree, biological design is not supernatural. Many scientists and bioengineering specialists do a lot of biological design these days too. Software design is not supernatural either. Engineers and computer scientists design complex machines and software all over the world these days. They don't perform miracles. They just study a lot and work very hard, for many years, using highly sophisticated technology. However, I have a few questions: What are the main issues of contention here? Definition of design? What does it mean as an action? What does it mean as an object or a system? Determination of design? How to determine whether something is designed or not? Are the above issues interrelated? Are they associated with certain concepts we often encounter in discussions here in this site, like irreducible complexity, CSI, dFCSI (or is it dFSCI?), FSCO/I? Do all those things have to do with the 'D' in 'ID'? Is the 'I' in ID a cause of contention? Is there a problem with the definition of the term? Or is the application of the term to particular cases? Perhaps this post will turn so heavy off topic that may have to move out to another thread? Since the neo-Darwinian approach to interpretation, with their formula (RM + NS + HGT + T +...= e) is under so much criticism these days, is Dr. Shapiro's 'third way' approach to interpretation of the observed biological objects the leading option now? Could ID be considered the 4th alternative? Is it possible that the third way might include ID at some point? The main web page of the third way site clearly distinguishes the first and second ways. But they don't seem to refer explicitly to the ID way. Obviously we would have to ask them why not. Any guess? Thank you in advance for any comments on this. BTW, my 'learning phase' is approaching its end. Soon I may have to move on to work on the next phase of the project I'm involved in. I'll try to keep an eye on this blog, specially the discussions that attract me most, including your insightful commentaries. But it's possible that my spare time will be much more limited.Dionisio
February 21, 2015
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Zachriel, Queen of the double-talk- mostly meandering nonsense that doesn't address what is being discussed.Joe
February 20, 2015
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Box: The starting point is pretty irrelevant in Wagner’s hyperastronomical library in 5,000-dimensional space, since about everything is interconnected – that’s the whole bizarre point. It still depends on the particulars of the landscape, though it will be much more connected in higher dimensions than in naïve notions of a two-dimensional landscape. Box: What exactly do you think that you and GPuccio agree on? The reasonable list of complex processes; adhesion, differentiation, apoptosis; in other words, it was an historical process. Dionisio: To me, it’s much more important for science today to dedicate more time and resources to the research of the biological systems and their functioning. There's a huge amount of time and resources dedicated to research of biological systems and their functioning, especially human biology; but sure, more would be nice. Dionisio: Unfortunately some delays might have been indirectly caused by misleading presuppositions based on unfounded worldview positions, which kept researchers from being open-minded and thinking out of the box. It's only natural for humans to explore blind alleys—you never know what you'll find until you look—; but to which "unfounded worldview positions" are you referring? Silver Asiatic: brief, reasonable, ambiguous comments pointing out that we don’t know certain things and referencing other works which are equally ambiguous and speculative. As scientists don't claim to have a working theory of abiogenesis, it is reasonable to qualify any such claims. Silver Asiatic: When an expert says “it could have happened this way” then supposedly that provides a sufficient answer to any and every problem. No. It calls for evidence. So if someone hypothesizes that lipid vacuoles might grow and divide spontaneously, then this is something that can be tested. Similarly, if someone claims that RNA may have the capability of self-replication, then this too might be subject to testing. Dionisio: That question was implicitly answered in post #506. As there is no complete theory of abiogenesis, there is no "comprehensive, logically coherent, step-by-step explanation". However, that hardly means that the work at Szostak's lab is irrelevant. gpuccio: But there is no doubt that an historical pattern exists. Common ground! gpuccio: With many sudden jumps (OOL, origin of eukaryota, origin of metazoa, Cambrian explosion, and probably many others). Our knowledge of those processes certainly is more finely gradated than what you suggest. For instance, adhesion exists in single-celled and simple colonial organisms.Zachriel
February 20, 2015
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Thanks, Gpuccio. That's a very nice way to say it. :-)Silver Asiatic
February 20, 2015
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Zachriel: "Good, so we agree we have evidence of the broad historical outline." Now, let's try to understand what we agree upon. You say: "The basic history was adhesion then differentiation then apoptosis." I certainly agree that those processes are important parts of the development of metazoa. I am not sure of the sequence, or of the historical pattern (I doubt that you are, too). But there is no doubt that an historical pattern exists. As you know, I don't believe that biological design is a supernatural miracle. Not necessarily, at least (I try to have no prejudices). I am sure that design happens in time and space, and has a specific history of development. That is obvious from what we know. But it is design all the way. Complex solutions are found, complex programmes are implemented, and nothing of that happens by RV and NS. That is "the key", as you would say: a stepwise increase in complexity, by stepwise design. With many sudden jumps (OOL, origin of eukaryota, origin of metazoa, Cambrian explosion, and probably many others).gpuccio
February 20, 2015
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Silver Asiatic: My point is that Zachriel is (IMO!) an intelligent person in a very unhappy situation: he defends a position which he believes in, but which is indefensible. And he does it at his best. I appreciate his sincerity and intelligence. But his position is wrong. He has made the wrong choice. That's all.gpuccio
February 20, 2015
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#510 Zachriel
Did you not find the work at Szostak’s lab to be relevant?
That question was implicitly answered in post #506. What they show seems to indicate that it's mostly 'work in progress' with no foreseeable end timing, which confirms that even most eminent scientists can't explain OOL in a comprehensive and logically coherent way. Is that relevant? :)Dionisio
February 20, 2015
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gpuccio
OK, the final result is that Zachriel has said a few effective things, most of them undeniable, some of them vague, all of them essentially reasonable, all of them intelligent in their form, which give the idea that there are a lot of important things that you don’t know, and that you are not considering, and that, while you have your arguments, those arguments can be essentially addressed.
You're being very considerate and charitable - and that's good. And yet I think you're also saying that we could go on-and-on forever with discussions in this vein ... brief, reasonable, ambiguous comments pointing out that we don't know certain things and referencing other works which are equally ambiguous and speculative. When an expert says "it could have happened this way" then supposedly that provides a sufficient answer to any and every problem. Decades of work building-out scenarios on how it 'could have happened' leading to the tiniest bits of confirmatory evidence create the illusion that we're 'getting closer' to the solution. No, actually we're not just getting closer, 'we already have the solution, we're merely filling in details'. Then we read someone like Wagner who gives us hyperastronomical libraries in multidimensional space, simply wiping the slate clean and claiming that there are pre-existing genetic networks that self-organize. So we can forget about Darwin on that point. What about the decades of 'gradualism research' that supposedly brought us ever-closer to the solution? I think that kind of thing exposes the ambiguity and uncertainty that surrounds the topic. But I'll also give Zachriel some praise - he always makes it sound like there's really nothing to question here at all. The science is settled, apparently. Even when we observe wildly conflicting stories on evolutionary origins (OOL research has an even greater variety of speculative scenarios) these are all presented as if there's nothing to be skeptical about at all, everything is basically progressing towards firm, materialist conclusions -- and the idea that there was some intelligence in the process is shut down completely. But the questions are far more open-ended that that. One look at this OP should reveal the challenge. So the attitude that seems as if the origins of even the most bafflingly interactive-complexity that we see are "basically settled" is revealing. It exposes an inconsistency - a defensiveness. It would be far more reasonable, and therefore convincing, if there was a real openness to the possibility of intelligent design. When that possibility is shut down or ridiculed, in favor of virtually any other imaginary materialist proposal, it's easy to see a bias at work.Silver Asiatic
February 20, 2015
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#510 Zachriel
What research is that?
Sorry, but I'm far from being "a master of language and clever expression" like you (according to gpuccio @507). Please, note that post #509 starts with the phrase: "#508 corrections". Hence, the piece of text that was quoted and corrected in post #509 was originally within the comment posted @508, therefore it must be read within that original context:
To me, it’s much more important for science today to dedicate more time and resources to the research of the biological systems and their functioning. There are many outstanding questions to be answered in those areas. Medicine and health maintenance programs could benefit much more from that research.
The rest of the comment in post #509 is an addendum to the previously quoted text correction:
And it’s actually benefitting from it already. Unfortunately some delays might have been indirectly caused by misleading presuppositions based on unfounded worldview positions, which kept researchers from being open-minded and thinking out of the box. Thus for years scientists either expected too much from certain things or too little from others. Fortunately these days apparently some gross misconceptions are being clarified and research seems heading in the right direction, producing an overwhelming avalanche of data that must be carefully analyzed. These are fascinating times to watch what’s going on in biology research.
Dionisio
February 20, 2015
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Zachriel,
gpuccio: Well, a reasonable list of complex processes which certainly have an important role.
Zachriel: Good, so we agree we have evidence of the broad historical outline.
In post #507 Gpuccio calls you "a master of language and clever expression", but this childish attempt is not a good example of your trickiness. What exactly do you think that you and GPuccio agree on? What "evidence"? What "historical outline"? Are you serious?Box
February 20, 2015
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Zachriel,
Box: So bacteria are able to find a flagellum in a few steps.
Zachriel: That depends on the starting point, of course.
The starting point is pretty irrelevant in Wagner’s hyperastronomical library in 5,000-dimensional space, since about everything is interconnected - that's the whole bizarre point.Box
February 20, 2015
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Dionisio: I did not find, in the sources you suggested*, any comprehensive, logically coherent, step-by-step explanations of how the bacteria or the first multicellular organisms could have appeared. Z: You’re choosing very ancient transitions that have left little physical evidence. The origin of the first cells is obscure. Did you not find the work at Szostak's lab to be relevant? gpuccio: Well, a reasonable list of complex processes which certainly have an important role. Good, so we agree we have evidence of the broad historical outline. As for adhesion, we have some evidence of its evolutionary origin. See Abedin & King, Diverse evolutionary paths to cell adhesion, Trends in Cellular Biology 2010; or Miller et al., The evolutionary origin of epithelial cell-cell adhesion mechanisms, Current Topics in Membranes 2013. Dionisio: Medicine and health maintenance programs could benefit much more from that research. What research is that?Zachriel
February 20, 2015
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#508 corrections
Personally I don’t know exactly how or when it happened, but I believe in its supernatural cause.
Medicine and health maintenance programs could benefit much more from that research.
And it's actually benefitting from it already. Unfortunately some delays might have been indirectly caused by misleading presuppositions based on unfounded worldview positions, which kept researchers from being open-minded and thinking out of the box. Thus for years scientists either expected too much from certain things or too little from others. Fortunately these days apparently some gross misconceptions are being clarified and research seems heading in the right direction, producing an overwhelming avalanche of data that must be carefully analyzed. These are fascinating times to watch what's going on in biology research.Dionisio
February 20, 2015
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gpuccio I'm glad you've clarified this so well for me. I really appreciate it. Hopefully onlookers/lurkers will benefit from reading your comments too (your OP has been visited 1260 times so far). I wasn't familiar with the suggested sources or their authors, hence I thought it was worth taking a look at them. I'm not a big fan of getting too involved in OOL debates. Personally I don't know how or when it happened, but I believe it has a supernatural cause. Besides, OOL debate doesn't seem to offer much value to my software development project. However, it's an important part of the ongoing debate in this site and outside. To me, it's much more important for science today to dedicate more time and resources to the research of the biological systems and their functioning. There are many outstanding questions to be answered in those areas. Medicine and health maintenance programs benefits much more from that research. Among your very insightful comments, you wrote:
Just think of what “differentiation” implies, for example.
Differentiation could be preceded by the highly complex mechanisms of specification and determination. All that together seems like a whole branch of the most advanced biology research these days. Just look at the numerous related references posted in the 'third way' and the 'mystery' threads in UD since last summer. That's why words like 'differentiation' in Z's post attracted my attention and made me look into the suggested sources. But all I found there was a combination of general ideas mixed with some specific references to a few fundamental properties that could be part of an explanation, but were not the explanations themselves. BTW, one of the suggested sources is around 12 years old, which seems like a very long time in light of the fast-paced biology research these days. I have seen more recent papers on the evolutionary topic, but they seem to lack the explanations requested in posts #440 and 501. However, my poor biological knowledge might have kept me from noticing the explanations. That's why I insist that those who know more provide the references and indicate the page numbers where the requested explanation is to be found. Quoting some related text could help too. Apparently nothing that meets those requirements has been presented here so far. Again, thank you very much for your timely commentary.Dionisio
February 20, 2015
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Dionisio: Zachriel is a master of language and clever expression, and that's why I appreciate him so much. Look at this masterpiece: "You’re choosing very ancient transitions that have left little physical evidence." Who could deny that? "The origin of the first cells is obscure." The understatement of the century, but certainly true. "You might check out the work of Jack Szostak’s Lab for some general ideas how it was thought to have occurred." You certainly might. Indeed, you did. And you certainly found "some general ideas how it was thought to have occurred". You did. Very general, certainly, and not about what happened, but certainly about what "was thought to have occurred". "This is also somewhat enigmatic; " The second understatement of the century, but certainly true. "however, it is not as mysterious as the origin of the first cell." Not sure, but it is probably true. Let's say that we could reasonably agree. "The basic history was adhesion then differentiation then apoptosis." Well, a reasonable list of complex processes which certainly have an important role. None of them explained. Just think of what "differentiation" implies, for example. "See this review; Müller, The Origin of Metazoan Complexity: Porifera as Integrated Animals, Integrative and Comparative Biology 2003." Certainly a reasonable advice: looking at what has been said about an issue is certainly a reasonable step in making up our ideas. "The key is the stepwise increase in complexity." This is masterful. Look at that word, "stepwise". He did not say "gradual", which is something I would have certainly agreed with, in general terms (who can deny that graduality is there, often together with sudden jumps?). And he did not say that "stepwise increase" was all that there is, only that it is the key to something. And what does "stepwise" mean? All and nothing. What is a "step"? One bit? The emergence of a new protein? Of a new pathway? Of a new species? And so on... Everything can be a "step". OK, the final result is that Zachriel has said a few effective things, most of them undeniable, some of them vague, all of them essentially reasonable, all of them intelligent in their form, which give the idea that there are a lot of important things that you don't know, and that you are not considering, and that, while you have your arguments, those arguments can be essentially addressed. A final consideration: I am not criticizing Zachriel at all. As I have said many times, I really like him, and there is no irony in this. He is intelligent, and generally respectful. This post of mine should be considered a tribute. :)gpuccio
February 19, 2015
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#504 Zachriel I did not find, in the sources you suggested*, any comprehensive, logically coherent, step-by-step explanations of how the bacteria or the first multicellular organisms could have appeared. Perhaps my ignorance didn't allow me to see it clearly? Can someone else point to the page numbers (from-to) where those explanations are written in? Thanks. Besides, the more specific challenge summarized in post #440 remains undisputed. (*) suggested sources http://molbio.mgh.harvard.edu/szostakweb/ http://www.jstor.org/discover/10.2307/3884834?sid=21105399959251&uid=2&uid=3739256&uid=4&uid=3739600 http://icb.oxfordjournals.org/content/43/1/3.fullDionisio
February 19, 2015
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#504 Zachriel Ok, will look into them. Thank you.Dionisio
February 19, 2015
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Dionisio: However, since now the number of hypothetical steps has been reduced so drastically, can someone provide reference to serious peer-reviewed scientific paper(s) containing comprehensive, logically coherent, step-by-step explanations of how the bacteria could have appeared You're choosing very ancient transitions that have left little physical evidence. The origin of the first cells is obscure. You might check out the work of Jack Szostak's Lab for some general ideas how it was thought to have occurred. http://molbio.mgh.harvard.edu/szostakweb/ Dionisio: and how the first multicellular organisms could have appeared? This is also somewhat enigmatic; however, it is not as mysterious as the origin of the first cell. The basic history was adhesion then differentiation then apoptosis. See this review; Müller, The Origin of Metazoan Complexity: Porifera as Integrated Animals, Integrative and Comparative Biology 2003. The key is the stepwise increase in complexity.Zachriel
February 19, 2015
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Box and Zachriel: Excuse me, but apparently what I can understand of Wagner's "argument" is the following: a) If we have a set of 5000 metabolic pathways b) If we describe each member of the set as "off" (0) or "on" (1) c) We have a set of 2^5000 states and d) We can go from one state to another one by turning on or off a single metabolic pathway. Is that all? Is it really that trivial? And what has that to do with the search for a functional state in a search space which is huge? A few simple questions: 1) The set of 5000 metabolisms is a hugely complex dictionary. Where did it come from? 2) Turning on or off a metabolic pathway can be a one bit operation, if the metabolic pathway is there and there is a one bit switch which can turn it on or off. That's what happened with the citrate pathway in the Lenski experiment. But where did the metabolic pathway come from? 3) Again, I cannot see the "multidimensional space". We have a set of 2^5000 states. We imagine that we can change the bits of each state. That is similar to a search for a functional protein in the sequence space, but the sequence space is made of random aminoacid sequences, while this "space" is made of complex and functional metabolisms. 4) That said, it remains to be seen how many of the 2^5000 combinations are functional, and naturally selectable. Frankly, I could not care less. The whole discourse is, up to now, utterly senseless. If anyone can make sense of it, please talk!gpuccio
February 19, 2015
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gpuccio Who would have thought that your OP will reach over 500 follow-up posted comments, but not a single serious counterargument for the challenging references summarized in post #440? Your interlocutors have let us down. What a disappointment. They sounded more knowledgeable and capable before you started this OP. At least that was the wrong perception I got when I read sparc's challenging comments that triggered your OP. Oh well, what else is new?Dionisio
February 19, 2015
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Ok, I admit that this off topic discussion on multidimensional search spaces is very high above my pay grade. However, since now the number of hypothetical steps has been reduced so drastically, can someone provide reference to serious peer-reviewed scientific paper(s) containing comprehensive, logically coherent, step-by-step explanations of how the bacteria could have appeared and how the first multicellular organisms could have appeared? Please, provide links and corresponding page numbers to locate the text. Thanks.Dionisio
February 19, 2015
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Box: So bacteria are able to find a flagellum in a few steps. That depends on the starting point, of course. Box: Are Wagner’s ideas gaining ground in mainstream biology? We're not familiar with Wagner's ideas, however, we are familiar with multidimensional search spaces.Zachriel
February 19, 2015
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Zachriel: What it means is that the probability of disconnected islands is vanishingly small. It also means there are many dimensional directions that can lead to increased fitness, many ‘ways’ to climb.
Yes, indeed. So bacteria are able to find a flagellum in a few steps. However one has to believe in Wagner's hyperastronomical library in 5,000-dimensional space in order to find such a scenario feasible. Are Wagner's ideas gaining ground in mainstream biology?Box
February 19, 2015
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