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What are the limits of Random Variation? A simple evaluation of the probabilistic resources of our biological world

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Coming from a long and detailed discussion about the limits of Natural Selection, here:

I realized that some attention could be given to the other great protagonist of the neo-darwinian algorithm: Random Variation (RV).

For the sake of clarity, as usual, I will try to give explicit definitions in advance.

Let’s call RV event any random event that, in the course of Natural History, acts on an existing organism at the genetic level, so that the genome of that individual organism changes in its descendants.

That’s more or less the same as the neo-darwinian concept of descent with modifications.

A few important clarifications:

a) I use the term variation instead of mutation because I want to include in the definition all possible kinds of variation, not only single point mutations.

b) Random here means essentially that the mechanisms that cause the variation are in no way related to function, whatever it is: IOWs, the function that may arise or not arise as a result of the variation is in no way related to the mechanism that effects the change, but only to the specific configuration which arises randomly from that mechanism.

In all the present discussion we will not consider how NS can change the RV scenario: I have discussed that in great detail in the quoted previous thread, and those who are interested in that aspect can refer to it. In brief, I will remind here that NS does not act on the sequences themselves (IOWs the functional information), but, if and when and in the measure that it can act, it acts by modifyng the probabilistic resources.

So, an important concept is that:

All new functional information that may arise by the neo-darwinian mechanism is the result of RV.

Examining the Summers paper about chloroquine resistance:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4035986/

I have argued in the old thread that the whole process of generation of the resistance in natural strains can be divided into two steps:

a) The appearance of an initial new state which confers the initial resistance. In our example, that corresponds to the appearance of one of two possible resistant states, both of which require two neutral mutations. IOWs, this initial step is the result of mere RV, and NS has no role in that. Of course, the initial resistant state, once reached, can be selected. We have also seen that the initial state of two mutations is probably the critical step in the whole process, in terms of time required.

b) From that point on, a few individual steps of one single mutation, each of them conferring greater resistance, can optimize the function rather easily.

Now, point a) is exactly what we are discussing in this new thread.

So, what are the realistic powers of mere RV in the biological world, in terms of functional information? What can it really achieve?

Another way to ask the same question is: how functionally complex can the initial state that for the first time implements a new function be, arising from mere RV?

And now, let’s define the probabilistic resources.

Let’s call probabilistic resources, in a system where random events take place, the total number of different states that can be reached by RV events in a certain window of time.

In a system where two dies are tossed each minute, and the numbers deriving from each toss are the states we are interested in, the probabilistic resources of the system in one day amount to  1440 states.

The greater the probabilstic resources, the easier it is to find some specific state, which has some specific probability to be found in one random attempt.

So, what are the states generated by RV? They are, very simply, all different genomes that arise in any individual of any species by RV events, or if you prefer by descent with modification.

Please note that we are referring here to heritable variation only, we are not interested to somatic genetic variation, which is not transmitted to descendants.

So, what are the probabilistic resources in our biological world? How can they be estimated?

I will use here a top-down method. So, I will not rely on empirical data like those from Summers or Behe or others, but only on what is known about the biological world and natural history.

The biological probabilstic resources derive from reproduction: each reproduction event is a new state reached, if its genetic information is different from the previous state. So, the total numbet of states reached in a system in a certain window of time is simply the total number of reproduction events where the genetic information changes. IOWs, where some RV event takes place.

Those resources depend essentially on three main components:

  1. The population size
  2. The number of reproductions of each individual (the reproduction rate) in a certain time
  3. The time window

So, I have tried to compute the total probabilistic resources (total number of different states) for some different biological populations, in different time windows, appropriate for the specific population (IOWs, for each population, from the approximate time of its appearance up to now). As usual, I have expressed the final results in bits (log2 of the total number).

Here are the results:

 

Population Size Reproduction rate (per day) Mutation rate Time window Time (in days) Number of states Bits + 5 sigma Specific AAs
Bacteria 5.00E+30 24 0.003 4 billion years 1.46E+12 5.26E+41 138.6 160.3 37
Fungi 1.00E+27 24 0.003 2 billion years 7.3E+11 5.26E+37 125.3 147.0 34
Insects 1.00E+19 0.2 0.06 500 million years 1.825E+11 2.19E+28 94.1 115.8 27
Fish 4E+12 0.1 5 400 million years 1.46E+11 2.92E+23 78.0 99.7 23
Hominidae 5.00E+09 0.000136986 100 15 million years 5.48E+09 3.75E+17 58.4 80.1 19

The mutation rate is expressed as mutations per genome per reproduction.

This is only a tentative estimate, and of course a gross one. I have tried to get the best reasonable values from the sources I could find, but of course many values could be somewhat different, and sometimes it was really difficult to find any good reference, and I just had to make an educated guess. Of course, I will be happy to acknowledge any suggestion or correction based on good sources.

But, even if we consider all those uncertainties, I would say that these numbers do tell us something very interesting.

First of all, the highest probabilistic resources are found in bacteria, as expected: this is due mainly to the huge population size and high reproduction rate. The number for fungi are almost comparable, although significantly lower.

So, the first important conclusion is that, in these two basic classes of organisms, the probabilistic resources, with this hugely optimistic estimate, are still under 140 bits.

The penultimate column just adds 21.7 bits (the margin for 5 sigma safety for inferences about fundamental issues in physics). What does that mean?

It means, for example, that any sequence with 160 bits of functional information is, by far, beyond any reasonable probability of being the result of RV in the system of all bacteria in 4 billion years of natural history, even with the most optimistic assumptions.

The last column gives the number of specific AAs that corrispond to the bit value in the penultimate column (based on a maximum information value of 4.32 bits per AA).

For bacteria, that corresponds to 37 specific AAs.

IOWs, a sequence of 37 specific AAs is already well beyond the probabilistic resources of the whole population of bacteria in the whole world reproducing for 4 billion years!

For fungi, 147 bits and 34 AAs are the upper limit.

Of course, values become lower for the other classes. Insects still perform reasonably well, with 116 bits and 27 AAs. Fish and Hominidae have even lower values.

We can notice that Hominidae gain something in the mutation rate, which as known is higher, and that I have considered here at 100 new mutations per genome per reproduction (a reasonable estimate for homo sapiens). Moreover, I have considered here a very generous population of 5 billion individuals, again taking a recent value for homo sapiens. These are  not realistic choices, but again generous ones, just to make my darwinist friends happy.

Another consideration: I have given here total populations (or at least generous estimates for them), and not effective population sizes. Again, the idea is to give the highest chances to the neo-darwinian algorithm.

So, these are very simple numbers, and they should give an idea of what I would call the upper threshold of what mere RV can do, estimated by a top down reasoning, and with extremely generous assumptions.

Another important conclusion is the following:

All the components of the probabilistic resources have a linear relationship with the total number of states.

That is true for population size, for reproduction rate, mutation rate and time.

For example, everyone can see that the different time windows, ranging from 4 billion years to 15 million years, which seems a very big difference, correspond to only 3 orders of magnitude in the total number of states. Indeed, the highest variations are probably in population size.

However, the complexity of a sequence, in terms of necessary AA sites, has an exponential relationship with the functional information in bits: a range from 19 to 37 AAs (only 18 AAs) corresponds to a range of 24 orders of magnitude in the distribution of probabilistic resources.

Can I remind here briefly, without any further comments, that in my OP here:

I have analyzed the informational jump in human conserved information at the apperance of vertebrates? One important result is that 10% of all human proteins (about 2000) have an information jump from pre-vertebrates to vertenrates of at least (about) 500 bits (corresponding to about 116 AAs)!

Now, some important final considerations:

  1. I am making no special inferences here, and I am drawing no special conclusions. I don’t think it is really necessary. The numbers speak for themselves.
  2. I will be happy of any suggestion, correction, or comment. Especially if based on facts or reasonable arguments. The discussion is open.
  3. Again, this is about mere RV. This is about the neutral case. NS has nothing to do with these numbers.
  4. For those interested in a discussion about the possible role of NS, I can suggest the thread linked at the beginning of this OP.
  5. I will be happy to answer any question about NS too, of course, but I would be even more happy if someone tried to answer my two questions challenge, given at post #103 of the other thread, and that nobody has answered yet. I paste it here for the convenience of all:

Will anyone on the other side answer the following two simple questions?

1) Is there any conceptual reason why we should believe that complex protein functions can be deconstructed into simpler, naturally selectable steps? That such a ladder exists, in general, or even in specific cases?

2) Is there any evidence from facts that supports the hypothesis that complex protein functions can be deconstructed into simpler, naturally selectable steps? That such a ladder exists, in general, or even in specific cases?

Comments
Corey Delvine: "I do find it disgusting though, how the “science” behind the ID movement preys on the lack of knowledge most people have in the field of biology." There is no such thing as lack of knowledge in determining either the probabilistic resources of biological world or the ratio between target space and search space in a specific biological context. Given our biological knowledge these numbers are pretty easy to determine. The problem is that most researchers in the field of evolutionary biology deny them and resist them because it is imperative for them to continue to secure funding and employment. It always boils down to 'follow the money'. Getting paid for empty storytelling about unseen past events is easy money for them.forexhr
November 15, 2017
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"This is an error, in my world." With every word you type, it seems that Gpuucio's world is more and more different from the real world. In my world, the word protein refers to any segment of amino acids over 50 residues. This is also the typically accepted minimum length requirement to be called a protein among biologists. So once again, your argument is entirely dependent on your own personal definitions of biological terms, which is in opposition to common definitions. So no, no error on my part. You say that because the 57 amino acid segement is "just" a protein domain, and not a full-length protein, it doesn't support my claim. And for that you are either clueless, or a liar.Corey Delvine
November 15, 2017
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kurx78: "What’s exactly the point of arguing with you anyway?" There is certainly no point in discussing with Corey. His bad faith is obvious. However, it is often interesting to discuss about some of the things that Corey says. He has been a good source of inspiration for good debates. Hist quote of that paper (when he finally gave it) is interesting, because it allows a detailed discussion on some serious errors made by darwinists (both Corey and the authors of the paper). If I can find the time to complete that discussion! :)gpuccio
November 15, 2017
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Corey Delvine: "I do find it disgusting though, how the “science” behind the ID movement preys on the lack of knowledge most people have in the field of biology. They construct houses of cards much like gpuccio has done here, that are based on strawman arguments (as I have continually pointed out) and simply baseless/untrue claims about the current evolutionary theory. I’m just doing my part to push back, no matter how futile." Don't be humble. You are an hero!gpuccio
November 15, 2017
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Corey Delvine: You should at least leave me the time to complete my reasoning. I was still at the very first premises. However, it is absolutely true that a first important error in your statement has been demonstrated. You said: "experiments have swapped amino acids in proteins, heck they’ve even stripped all 20 amino acids away and rebuilt proteins using only 4 amino acids and the protein was still functional" Your statement refers explicitly to proteins, and then in particular to a protein. But the paper you quoted is about a protein domain, a short protein domain which is part of much longer proteins. This is an error, in my world. I am not complaining about the paper (not yet, at least). I am pointing to an explicit error in your statement, an important error that could certainly mislead those who read your comment and have great faith in what you say (I am not part of the lot) to believe that entire proteins, probably a lot of them, or at least one entire protein, had been, as you say, "stripped away of all 20 amino acids away and rebuilt using only 4 aminoacids, and the protein was still functional". That is simply false. Your statement is wrong about that, and can only generate false convictions. I am simply pointing to that undeniable error. Am I "clueless or a liar" for that? However, that was only a premise to my criticism of your statement, and in part of the paper itself. Please, be patient and give me the time to write other clueless lies.gpuccio
November 15, 2017
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Things are more interesting and fun when you do it my way Kurx, and I just like to push people's buttons. And I couldn't care less about how I am perceived here. I do find it disgusting though, how the "science" behind the ID movement preys on the lack of knowledge most people have in the field of biology. They construct houses of cards much like gpuccio has done here, that are based on strawman arguments (as I have continually pointed out) and simply baseless/untrue claims about the current evolutionary theory. I'm just doing my part to push back, no matter how futile.Corey Delvine
November 15, 2017
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I just see more Ad Hominems... and that's quite sad. It's sad because even if gpuccio is wrong with his argumentation, you are totally unable to sustain an educated discussion, you just want to humiliate, to denigrate, to destroy and that speaks very low of you as a professional and a scientist. (In case you are one) As an engineer and scientist I always try to keep my discussions educated and polite. Every dialog with someone else is an oportunity to learn new things and examine my own findings. That's what good science is about, to question, to examine and improve our understanding of the natural world. You are not contributing to this conversation, you are just throwing ramblings and barking trees. I may disagree with people like Critical Rationalist or rvb8 but his contributions to the dialog sometimes are amazing and very thoughtful. What's exactly the point of arguing with you anyway?kurx78
November 15, 2017
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Gpucc, if you are complaining that they only altered a domain of a protein then you are ignorant of molecular biology techniques. If you had actually read the paper instead of just the abstract, you'd see that even for this short amino acid segment, they had to break it up into 3 sections to generate variant libraries. So once again, much like your demand that researchers build an entire ecosystem to demonstrate selectability and therefore function, you are simply being ridiculous. For you to say that the paper doesn't support what I have said because it's a domain and not an entire protein, means you are either clueless or a liar. So which is it?Corey Delvine
November 15, 2017
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Corey Delvine: It is funny to see how you attack the character of gpuccio just because he is demonstrating mathematically and empirically that there hasn't been enough fuel for evolution to occur. Evolution is a nice theory on paper - we have a population and its gene pool which is steadily changed due to mutations and new sexual recombinations of genes. Natural selection then sorts out the useful changes in the gene pool and population evolves. Beneficial new genes quickly spread through the population because members who carry them have a greater reproductive success or evolutionary fitness. But, what is ignored in this theoretical approach is whether changes that entered the gene pool during some evolutionary period are sufficient to explore the sequence space of some duplicated genes and find ones that are beneficial. Empirical science and mathematics answered a very definite 'no' to this question since gene sequence space is extremely sparsely populated by genes that are beneficial in the environment to which the population is exposed. For e.g., human population has been exposed to aquatic environments for a hundred thousand generations and tons and tons of mutations have entered its gene pool, but no beneficial gens (for breathing under water) have been found. This is because the ratio between non-beneficial and beneficial genes for this specific environment is so large that even if all mutations which have occurred in the evolutionary history are spent, no genes for breathing under water would enter the gene pool of human population. Simply put, there hasn't been enough fuel for evolution to run. A this is what gpuccio is trying to tell you. But instead of accepting or at least exploring this simple and obvious scientific truth, you attack the person who posted it. Though, what can you expect from a Darwinist?forexhr
November 15, 2017
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Corey Delvine: Here are the answers about your statement and the paper you quoted to support it. Your statement was (at #171):
experiments have swapped amino acids in proteins, heck they’ve even stripped all 20 amino acids away and rebuilt proteins using only 4 amino acids and the protein was still functional
And the paper you quote in support of that statement is the following: "Functional rapidly folding proteins from simplified amino acid sequences" https://www.nature.com/articles/nsb1097-805 The article is of 1997, not exactly recent, but that's not a problem. Now, the question is: does that paper support your statement? The answer, of course is: no! Let's see why. Here is the abstract: "Early protein synthesis is thought to have involved a reduced amino acid alphabet. What is the minimum number of amino acids that would have been needed to encode complex protein folds similar to those found in nature today? Here we show that a small ?-sheet protein, the SH3 domain, can be largely encoded by a five letter amino acid alphabet but not by a three letter alphabet. Furthermore, despite the dramatic changes in sequence, the folding rates of the reduced alphabet proteins are very close to that of the naturally occurring SH3 domain. This finding suggests that despite the vast size of the search space, the rapid folding of biological sequences to their native states is not the result of extensive evolutionary optimization. Instead, the results support the idea that the interactions which stabilize the native state induce a funnel shape to the free energy landscape sufficient to guide the folding polypeptide chain to the proper structure." A little bit vague, I would say. But we will see more details in our discussion. First of all, what did they experiment with? Not "a protein", as you incorrectly state, but a protein domain. Moreover, a very small protein domain: the SH3 domain. Now, this domain is not only small (in the paper, it is given as 57 AAs long), but represents also a big protein superfamily in SCOP: 1shf. This superfamily includes many different proteins, which share a similar folding and structure, a beta-sheet based structure, but have rather different sequences and functions. See for example the Wikipedia page on the domain, here: https://en.wikipedia.org/wiki/SH3_domain We will come back to these points later. So, what particular SH3 domain sequence was used in our paper? well, it is not completely clear (they just call it "src SH3 domain" in the Methods seciton). But, luckily, they give the full sequence. Here it is: TFVALYDYESRTETDLSFKKGERLQIVNNTEGDWWLAHSLSTGRTGYIPSNYVAPSD Now, that's strange, because blasting that sequence I could find no identical sequence in the Blast database. However, the sequence is almost identical to the SH3 domain in one human protein (and in other vertebrate proteins): Proto-oncogene tyrosine-protein kinase Src, P12931, 536 AAs long. Almost identical: 56 identities + 1 positive (the R in position 44). As I could find no better hit I will consider the sequence as the domain from that human protein, for all practical purposes. That this domain is a short and rather simple domain can be verified, for example, looking at this paper: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2143930/pdf/9521098.pdf Fig. 6 C. The paper gives domain length as ranging from 36 to 692 AAs, and peaking around 100. With 57, we are here certainly in the lower tail of the distribution, probably about 10th - 20th percentile. This is important, because shorter domains are of course, in average, less complex. The function of the SH3 domain is, in general, to bind something, usually (but not always) peptides. From Wikipedia:
The classical SH3 domain is usually found in proteins that interact with other proteins and mediate assembly of specific protein complexes, typically via binding to proline-rich peptides in their respective binding partner.
OK, no more time now. More in next post, later.gpuccio
November 15, 2017
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Corey Delvine: OK, we are at name calling at last! Good. :) However, in the midst of name calling, it seems that you have found your lost reference. Good. :) “Functional rapidly folding proteins from simplified amino acid sequences” Now, I can answer in detail to your statements. But I have not the time now, because it requires some work, and you certainly deserve it. I hope later today! In the meantime, as you have again "not-quoted" another paper: "Baker’s work has also shown that typically 95% of residues tolerate amino acid susbtitutions." which seems to be on a similar subject, could you please find the reference for it too, so that I can answer about that too? Sorry to ask you for so much work! :)gpuccio
November 15, 2017
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Corey Delvine:
Look, the complex cells of today are extremely different from the first living protocells, we’re going to have to speak somewhat hypothetically about ATP-binding/function while also grounding ourselves in basic biochemical processes.
I have some of the first living protocells right here next to me and they are at least as complex as any modern cell and very much the same. Of course, you would just look at them and compare them to modern cells and declare ex cathedra that they could not possibly be ancient protocells because they are far too much like modern cells. Of course, that is just begging the question. But hey, if that's all you have!Mung
November 14, 2017
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I’m sure you’re happy about that, Gpuccio, because you wouldn’t survive in the ballpark of actual scientific research.
Could have predicted the insults were coming.Mung
November 14, 2017
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I'm sure you're happy about that, Gpuccio, because you wouldn't survive in the ballpark of actual scientific research. Peer-review is the standard metric for today's scientific research. Without some sort of peer-review, your claims are not scientific and, but mere Gpuccio pipe-dreams; and hence you will remain in the realm of "scientific." That is unless I can win a nobel for just claiming to have cured cancer. Ah, I see, you judge the merit of scientific research based on the number of times the word "design" pops up. Got it. You should know this stuff already gpucc, if you're going to try to talk about protein evolution. "Functional rapidly folding proteins from simplified amino acid sequences" It was five amino acids, not four though (excuse me!). Baker's work has also shown that typically 95% of residues tolerate amino acid susbtitutions. Look, the complex cells of today are extremely different from the first living protocells, we're going to have to speak somewhat hypothetically about ATP-binding/function while also grounding ourselves in basic biochemical processes. If your lack of knowledge about molecular biology keep you from doing this, then I apologize. Also, just FYI, you can do all this "science" within R, but maybe it's an "old dog, new tricks" issue.Corey Delvine
November 14, 2017
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EugeneS: OK, I have just published an OP about bioinformatics tools. I hope you may enjoy it! :)gpuccio
November 14, 2017
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gpuccio @196: Your assessment of the bottom line message of the paper referenced @195 is right on target. The author's disclaimer confirms it: "As a disclaimer, I should note that no attempt is made here on anything close to a comprehensive review of the research on the code origin and evolution let alone the origin of life. The goal is to place the frozen accident concept into the context of latest efforts in the field and briefly discuss some new ideas." BTW, they have more on that topic -including another paper by Koonin here: http://www.annualreviews.org/doi/10.1146/annurev-genet-120116-024713Dionisio
November 14, 2017
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gpuccio @191: "If I really swept all stupid and wrong statements under my rug, I could never use my rug again. Let’s say that I am satisfied with showing that they are stupid and/or wrong." That rug would have to be thrown into a special container for highly contaminated trash.Dionisio
November 14, 2017
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gpuccio @196: Thanks for the insightful commentary.Dionisio
November 14, 2017
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CD:
Sorry, but Gpuccio’s track record pales in comparison to the body of work that supports evolution.
What body of work supports evolution by means of blind, mindless processes?
Evolution does not look for a specific target. Certainly not in sequence space.
And yet you expect us to believe it found it many, many, many times over. How much sheer dumb luck does your position require?ET
November 14, 2017
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Dionisio: I can easily quote myself (post #155, answering you): "Well, the 3 papers you quote are, in a sense, honest enough, because they clearly show how little we understand of the issue! They are all of the type: we understand practically nothing of how this happened, but let me suggest some new revealing idea! Of course, after the revealing idea is given, we still understand practically nothing." That could well apply to this recent paper by Koonin. While it is interesting and detailed in explaining why all existing theories about the origin of the genetic code are trash, it is completely vague and unconvincing in trying to suggest some new form of trash. However, my point was not so much about how the genetic code originated (which remains an absolute mystery): my point was rather that, anyway, all the existing information in RNA molecules cannot be transmitted to a new symbolic code of information.gpuccio
November 14, 2017
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gpuccio @159:
“A regulatory function linked to the biochemical structure of the nucleotide sequence has nothing to do with the potential symbolic function of those same nucleotides to code for functional proteins.” is also the main reason (but not the only one) why the imagined transition from some hypothetical RNA world to a DNA-RNA-protein world (the only one we know to exist) is simply impossible.
gpuccio @167:
Let’s say that we have a sequence of nucletodes A. Let’s say that, in the fabulous RNA world, sequence A is functional: it has some specific biochemical activity, for which it has been selected and preserved. The functional information in sequence A is also passed to new generations because, of course, a sequence of nucleotides can be copied by some RNA polymerase activity, effected by the RNA itself. This is, I suppose, the central idea for the RNA world: RNA can be both an effector molecule and an information storing molecule. Now, let’s say that we make the transition to an RNA-protein world. Let’s say that the function which was effected by A in the RNA world should now be inherited by a protein Ap. Well, there is absolutely no way that the information in A (the nucleotide sequence) can be “transferred” to some other nucleotide sequence (let’s call it A1) which can code for the protein Ap. Why? Because the information in A1 for Ap must of course be coded according to the symbolic genetic code. IOWs A1 (which should code for Ap) has absolutely no relationship with A (the nucleotide sequence which effected the function in the RNA world). They are two completely different types of information, because they have information for the same function, but in two completely different ways: a) A has information for an RNA molecule, whose 3d structure and biochemical activity depend directly on the nucleotide sequence, according to objective biochemical laws (IOWs, in the same way that a protein structure and function depend on its AA sequence). b) A1 has information for a sequence of AAs, corresponding to a functional protein, but that sequence of AAs, and therefore the structure and function of the protein, depend on the nucleotide sequence only symbolically, through an arbitrary code. So, there is absolutely no way that the information in A can generate the information in A1 by non design mechanisms. IOWs, the RNA world is no “precursor” to the protein world: all the information in the RNA world will be lost in the supposed transition to the protein world. IOWs, the protein world could as well arise from scratch, as far as functional information is concerned.
What about this?
Frozen Accident Pushing 50: Stereochemistry, Expansion, and Chance in the Evolution of the Genetic Code Eugene V. Koonin Life (Basel). 7(2): 22. doi: 10.3390/life7020022 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5492144/pdf/life-07-00022.pdf
Dionisio
November 14, 2017
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Corey Delvine:"...Evolution does not look for a specific target. Certainly not in sequence space." That's really an odd statement to make. Imagine that we have an ecological or environmental area that is inhabited by some organisms. Sources of food in this area are drying up and population of organisms is introduced to a new environment. In this new environment there are plenty of energy rich substances. But the problem is that genes for metabolic pathway to convert this substances into usable energy do not exist in a gene pool of that population. Metabolic pathway with such ability consists of two enzymes. Thus, the information that codes for these enzymes is not present in the DNA, just like information that codes for eyes, heart or wings was not present in the DNA of the first self-replicating organism. Question: if evolution does not look for a specific target(specific DNA sequences) in a sequence space of some junk DNA, then how do the adaptive sequences enter the gene pool of the population for natural selection to act on them and drive evolution? Do they appear, emerge, arose or burst onto the scene with the wave of a magic wand?forexhr
November 14, 2017
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CD, case proved as you can see for yourself. KFkairosfocus
November 14, 2017
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:) :) :)Upright BiPed
November 13, 2017
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Corey Delvine:
Sorry, but Gpuccio’s track record pales in comparison to the body of work that supports evolution. The two are not even in the same ballpark.
True. And I am very happy and proud of not being in that ballpark.
And yes, he is on trial; if Gpuccio is going to make “scientific” claims, someone should peer-review them.
I am making my claims here, at Uncommon Descent. I did not know that peer review was required. My claims can be scientific or not, anyone can judge. Certainly they are not "scientific", a category whose epistemological nature eludes me! :) Peer review is a requirement for publication in journals. I did not know that it was a requirement for statements to be scientific. Philosophy of science must have changed in the last few days, and I probably did not realize it. :)
Gpuccio, you should take a look at the work David Bakers lab has done on protein sequence/structure/function.
You mean the lab at the "Institute for Protein Design"? (emphasis mine) Whose last paper in Nature is about "building 20,000 new drug candidates"? I quote from their site: "This new method of drug development relies on the integration of computer modeling and laboratory testing to rapidly generate and evaluate tens of thousands of potential mini-protein binders with varying shapes. This unprecedented scale of de novo protein design was made possible by recent advances in both the Rosetta software suite and DNA manufacturing. Using this method, mini-protein binders can be rapidly programmed to target a range of proteins, including other viruses, toxins, or even tumor-specific markers." (emphasis mine) Perhaps you should explain better how work about protein engineering, where the word "design" recurs almost at every paragraph, is relevant to our discussion. I certainly can't see it.
The fact that you have to ask for references demonstrates what little knowledge you have in the field which you are attempting to contribute to.
Strange statement indeed! Asking for precise, explicit and relevant references is the first thing that all peer reviewers do when you submit any paper for publication. Are all peer reviewers, that you seem to love so much, completely ignorant "in the field they are attempting to contribute to"? In your comment at #171 you boldly stated: "heck they’ve even stripped all 20 amino acids away and rebuilt proteins using only 4 amino acids and the protein was still functional." I asked for a precise reference, because I don't believe that it is true, but of course, as I respect what you say and I cannot know everything that has been published, I would never say so without first giving you a chance to show that it is true, and that you are not just imagining things. Also, a precise reference would allow a discussion about specific statements. You seem to answer by referring vaguely to a lab that does, explicitly, protein engineering. If it was the Bakers lab that did what you say at #171, could you please specify the pertinent paper? I am not making any assumptions about the reasons why you apparently don't want to give any references about what you state, because that is anyone's guess.
More strawmen. Evolution does not look for a specific target. Certainly not in sequence space.
More strawmen from your part. Very specific targets have been found by evolution. And they have certainly been found in sequence space. I am discussing how evolution could find them, IOWs I am looking for some explanation for what we observe (the facts), which is what science is supposed to do. Your theory is that evolution was not looking for those targets, and yet in some way it found them in sequence space. That is exactly what I believe to be impossible, and I try to explain why. My theory is that evolution was guided by design to find those targets. So, no strawman at all. I am criticizing exactly what you believe.
ATP-binding could serve a number of functions, especially if we are considering the time period it originated (extremely early in life’s history). Binding ATP will stabilize the phosphate groups and limit auto-hydrolysis (preserving energy). Binding ATP can also act as a mechanism to increase its local concentrations. Binding ATP can be a basic energy storage mechanism by sequestering free ATP Binding ATP will also drive chemical reactions by affecting reactant/product ratios. There’s a few right off the top of my head.
So, I suppose that if I ask you any reference that shows with facts that Szostak's ATP binding proteins, implementing even one of those functions, can give a reproductive advantage in any real biological context, and therefore be naturally selectable, you will promptly give them? Or will you just accuse me of harassing you? Until then, let's say that you are just imagining things "off the top of your head".
Of course the poster-child of confirmation bias will find a way to sweep them under the rug along with everything else I say.
If I really swept all stupid and wrong statements under my rug, I could never use my rug again. Let's say that I am satisfied with showing that they are stupid and/or wrong.gpuccio
November 13, 2017
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"on very long and good track record, GP is not on trial." Sorry, but Gpuccio's track record pales in comparison to the body of work that supports evolution. The two are not even in the same ballpark. And yes, he is on trial; if Gpuccio is going to make "scientific" claims, someone should peer-review them. Anyways... Gpuccio, you should take a look at the work David Bakers lab has done on protein sequence/structure/function. The fact that you have to ask for references demonstrates what little knowledge you have in the field which you are attempting to contribute to. "in order for a specific target to be found" More strawmen. Evolution does not look for a specific target. Certainly not in sequence space. ATP-binding could serve a number of functions, especially if we are considering the time period it originated (extremely early in life's history). Binding ATP will stabilize the phosphate groups and limit auto-hydrolysis (preserving energy). Binding ATP can also act as a mechanism to increase its local concentrations. Binding ATP can be a basic energy storage mechanism by sequestering free ATP Binding ATP will also drive chemical reactions by affecting reactant/product ratios. There's a few right off the top of my head. Of course the poster-child of confirmation bias will find a way to sweep them under the rug along with everything else I say.Corey Delvine
November 13, 2017
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GPuccio "That’s a very good idea. I’ll do it." Thank you very much. "devil's advocate ... (which, after all, is a term from the Catholic tradition)" I meant I would not like to be called one. I should have used less emotionally loaded verb ;) Seriously, I consider your OPs as ones that belong to the golden fund of this blog!EugeneS
November 13, 2017
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EugeneS: "Second, I feel we need to give our interlocutors’ arguments a fair bit of attention (since they are not speaking up for themselves)" Yes, that's fair. And I must say that you friends who occasionally play the role of "devil's advocate" (which, after all, is a term from the Catholic tradition) are much better at it than our polite dissenters: you know the issues better, and you can formulate better counter-arguments, even if only for the sake of discussion! :) "I also have a couple of very concrete and probably very simple questions regarding the bioinformatics algorithms and software you are using. Could you write a post on the bioinformatics basics, the metrics and a little more detail about how you produced those graphs, for the benefit of the general audience?" That's a very good idea. I'll do it. "This is really valuable work." Thank you! :) "Please could you organize your contributions on the blog by author, so we can quickly find a publication." That's a very good idea, too. I support it, even if I don't know how easy it would be to implement it. Maybe Barry can give us some feedback about that.gpuccio
November 13, 2017
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GP, Barry and other contributors! Please could you organize your contributions on the blog by author, so we can quickly find a publication. Otherwise the interested reader has to create multiple bookmarks in the browser. I suggested creating an index by author way back but was not heard :)Eugene S
November 13, 2017
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GP "Of course this is only bad reasoning about probabilites." Exactly my thoughts on this! Thank you very much for the detailed answer. I wanted to synchronize the watches, so to speak. Second, I feel we need to give our interlocutors' arguments a fair bit of attention (since they are not speaking up for themselves) :) I hate the phrase "the advocate of the devil" even though I know that its connotation is not as dramatic as it may sound to somebody, like myself, whose native language is not English :) I have been extremely busy lately. I will eventually get through your other comments. I also have a couple of very concrete and probably very simple questions regarding the bioinformatics algorithms and software you are using. Could you write a post on the bioinformatics basics, the metrics and a little more detail about how you produced those graphs, for the benefit of the general audience? This is really valuable work.Eugene S
November 13, 2017
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