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The highly engineered transition to vertebrates: an example of functional information analysis

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In the recent thread “That’s gotta hurt” Bill Cole states:

I think over the next few years 3 other origins (my note: together with OOL), will start to be recognized as equally hard to explain:

  • The origin of eukaryotic cell: difficult to explain the origin of the spliceosome, the nuclear pore complex and chromosome structure.
  • The origin of multicellular life: difficult to explain the origin of the ability to build complex body plans.
  • The origin of man: difficult to explain the origin of language and complex thought.

That thought is perfectly correct. There are, in natural history, a few fundamental transitions which scream design more that anything else. I want to be clear: I stick to my often expressed opinion that each single new complex protein is enough to infer design. But it is equally true that some crucial points in the devlopment of life on earth certainly stand out as major engineering events. So, let’s sum up a few of them:

  1. OOL
  2. The prokaryote – eukaryote transition (IOWs, eukaryogenesis)
  3. The origin of metazoa (multicellular life)
  4. The diversification of the basic phyla and body planes (IOWs, the Cambrian explosion)

Well, saurian-1358308_1280to those 4 examples, I would like to add the diversification of all major clades and subphyla.

Of course, another fundamental transition is the one to homo sapiens, but I will not deal with it here: I fully agree with Bill Cole that it is an amazing event under all points of view, but it is also true that it presents some very specific problems, which make it a little bit different from all the other transitions we have considered above.

I will state now in advance the point that I am trying to make here: each of the transitions described requires tons and tons of new, original, highly specific functional information. Therefore, each of those transitions commands an extremely strong inference to design. I will deal in particular with the transition to the subphylum of vertebrates, for a series of reasons: being vertebrates, we are naturally specially interested in that transition; there are a lot of fully sequenced genomes and proteomes of vertebrate species ;  and a lot is known about vertebrate biology. IOWs, we have a lot of data that can help us in our reasoning. So, I will  try to fix a few basic points which will be the foundation of our analysis:

  • a) The basic phylum is Chordates, which are characterized by the presence of a notochord. Chordates include three different clades: Craniata, Tunicata, Cephalochordata.
  • b) Vertebrates are a subphylum of the phylum Chordates, and in particular of the clade Craniata. They represent the vast majority of Chordates, with  about 64,000 species described. As the name suggests, they are characterized by the presence of a vertebral column, either cartilaginous or bony, which replaces the notochord.
  • c) The phylum Chordate, like other phyla, can be traced at least to the Cambrian explosion (540 million years ago).
  • d) Chordates which are not vertebrates are quite rare today. They include:
    • 1) Craniata: the only craniates which are not vertebrates are in the class Myxini (hagfish), whose classification however remains somewhat controversial. All other craniates are vertebrates.
    • 2) Tunicata (or urochordata): about 3000 species, the best known and studied is Ciona intestinalis.
    • 3) Cephalochordata: about 30 species of Lancelets.
  • e) The phyla most closely related to Chordates are Hemichordates (like the Acorn worm) and Echinoderms (Starfish, Sea urchins, Sea cucumbers).
  • f) Vertebrates can be divided into the following two groups:
    • 1) Fishes: 3 Classes:
      • 1a) Jawless  (lampreys)
      • 1b)  Cartilaginous (sharks, rays, chimaeras)
      • 1c) Bony fish
    • 2) Tetrapods: all the rest (frogs, snakes, birds, mammals)

For the following analysis, I will consider vertebrates versus everything which preceded them (all metazoa, including “pre-chordates” (Hemichordates and Echinoderms) and “early chordates”  (Tunicata and Cephalochordata). So, everything which is new in vertebrates had to appear in the window between early chordates and the first vertebrates: cartilaginous fish and bony fish (I will not refer to lampreys, because the data are rather scarce). So, let’s try to define the temporal window, for what it is possible:

  • Chordates are already present at the Cambrian explosion, 540 my ago.
  • Jawless fish appeared slightly later (about 530 my ago), but they are mostly extinct.
  • The split of jawless fish into cartilaginous fish and bony fish can be traced about at 450 my ago

Therefore, with all the caution that is required, we can say that the information which can be found in both cartilaginous fish and bony fish, but not in non vertebrates (including early chordates), must have been generated in a window of less that 100 my, say between 540 my ago and 450 my ago. Now, my point is very simple: we can safely state that in that window of less than 100 million years a lot of new complex functional information was generated. Really a lot. To begin our reasoning, we can say that vertebrates are characterized by the remarkable development of two major relational systems:

  1. The adaptive immune system, which appears for the first time exactly in vertebrates.
  2. The nervous system, which is obviously well represented in all metazoa, but certainly reaches new important adaptations in vertebrates.

Muperch-62855_640ch can be said about the adaptive immune system, and that will probably be the object of a future OP. For the moment, however, I will discuss some aspects linked to the development of the nervous system. The only point that is important here is that the nervous system of vertebrates undergoes many important modifications, especially a process of encephalization.  My interest is mainly in the developmental controls that are involved in the realization of the new body plans and structures linked to those processes. Of course, we don’t understand how those regulations are achieved. But today we know much about some molecules, especially regulatory proteins, which have an important role in the embryonal development of the vertebrate nervous system, and in particular in the development and migration of neurons, which is obviously the foundation for the achievement of the final structure and function of the nervous system. So, I will link here a recent paper which deals with some important knowledge about the process of neuron migration. I invite all those interested to read it carefully: Sticky situations: recent advances in control of cell adhesion during neuronal migration by David J. Solecki Here is the abstract:

The migration of neurons along glial fibers from a germinal zone (GZ) to their final laminar positions is essential for morphogenesis of the developing brain, aberrations in this process are linked to profound neurodevelopmental and cognitive disorders. During this critical morphogenic movement, neurons must navigate complex migration paths, propelling their cell bodies through the dense cellular environment of the developing nervous system to their final destinations. It is not understood how neurons can successfully migrate along their glial guides through the myriad processes and cell bodies of neighboring neurons. Although much progress has been made in understanding the substrates (14), guidance mechanisms (57), cytoskeletal elements (810), and post-translational modifications (1113) required for neuronal migration, we have yet to elucidate how neurons regulate their cellular interactions and adhesive specificity to follow the appropriate migratory pathways. Here I will examine recent developments in our understanding of the mechanisms controlling neuronal cell adhesion and how these mechanisms interact with crucial neurodevelopmental events, such as GZ exit, migration pathway selection, multipolar-to-radial transition, and final lamination.

In brief, the author reviews what is known about the process of neuronal cell adhesion and migration. Starting from that paper and some other material, I have chosen a group of six regulatory proteins which seem to have an important role in the above process. They are rather long and complex proteins, particularly good for an information analysis. Here is the list. I give first the name of the protein, and then the length and accession number in Uniprot for the human protein:

  • Astrotactin 1,     1302 AAs,     O14525
  • Astrotactin 2,    1339 AAs,     O75129
  • BRNP1 (BMP/retinoic acid-inducible neural-specific protein 1),     761 AAs,     O60477
  • Cadherin 2 (CADH2),      906 AAs,    P19022
  • Integrin alpha-V,    1048 AAs,      P06756
  • Neural cell adhesion molecule 1 (NCAM1),   858 AAs,  P13591

This is a  very interesting bunch of molecules:

  • Astrotactin 1 and 2 are two partially related perforin-like proteins. ASTN-1 is a membrane protein which is directly responsible for the formation of neuron–glial fibre contacts. ASTN2 is not a neuron-glial adhesion molecule, but it functions in cerebellar granule neuron (CGN)-glial junction formation by forming a complex with ASTN1 to regulate ASTN1 cell surface recruitment. More about these very interesting proteins can be found in the following paper:

Structure of astrotactin-2: a conserved vertebrate-specific and perforin-like membrane protein involved in neuronal development by Tao Ni, Karl Harlos, and Robert Gilbert

  • BRNP1 is another  protein which functions in neural cell migration and guidance
  • Cadherin 2, or N-cadherin, is active in many neuronal funtions and in other tissues, and seems to have a crucial role in glial-guided migration of neurons
  • Integrin alpha-V, or Vitronectin receptor, is one of the 18 alpha subunits of integrins in mammals. Integrins are transmembrane receptors that are the bridges for cell-cell and cell-extracellular matrix (ECM) interactions.
  • NCAM1 is a cell adhesion molecule involved in neuron-neuron adhesion, neurite fasciculation, outgrowth of neurites

Now, why have I chosen these six proteins, and what do they have in common? They have two important things in common:

  • They are all big regulatory proteins, and they are all involved in a similar regulatory network which controls endocytosis, cell adhesion and cell migration in neurons, and therefore is in part responsible for the correct development of the vertebrate nervous system
  • All those six proteins present a very big informarion jump between pre-vertebrate organisms and the first vertebrates

The evolutionary history of those six protein is summarized in the following graph, realized as usual by computing the best homology bit score with the human protein in different groups of organisms.

Neuron_migration

Very briefly, all the six human molecules have low homology with pre-vertebrates, while they already show a very high homology  in cartilaginous fishes. The most striking example is probably Astrotactin 2, which presents the biggest jump from cephalochordata (329 bits) to cartilaginous fishes (1860 bits), for a great total of 1531 bits of jump! The range of individual jumps in the group is 745 – 1531 bits, with a mean jump of 1046 bits per molecule and a total jump of 6275 bits for all six molecules. The jump has always been computed as the difference between the best bit score in cartilaginous fishes and the best bitscore in all pre-vertebrate metazoa. We can also observe that the first three proteins have really low homology with everything up to tunicates, but show a definite increase in Cephalochordata, which precedes the big jump in cartilaginous fishes, while the other three molecules have a rather constant behaviour in all pre-vertebrate metazoa, with a few hundred bits of homology, before “jumping” up in sharks. One could ask: is that a common behaviour of all proteins? The answer is no. Look at the following graph, which shows the same evolutionary history for two other proteins, both of them very big regulatory proteins, both of them implied in the same processes as the previous six.

Neuron_migration2

Here, the behaviour is completely different. While there is a slight increase of homology in time, with a few smaller “jumps”, there is nothing comparable to the thousand bit jumps in the first six molecules. IOWs, these two molecules already show a very high level of homology to the human form in pre-vertebrates, and change only relatively little in vertebrates. We can say, therefore, that most of the functional information in these two proteins was already present before the transition to vertebrates.

So, to sum up:

  • a) The six proteins analyzed here all exhibit a huge informational jump between pre-vertebrates and vertebrates. The total functional informational novelty for just this small group of proteins is more than 6000 bits, with a mean of more than 1000 bits per protein.
  • b) These proteins are probably crucial agents in a much more complex regulation network implied in neuron adhesion, endocytosis, migration, and in the end in the vast developmental process which makes individual neurons migrate to their specific individual locations in the vertebrate body plan.
  • c) The above process is certainly much more complex than the six proteins we have considered, and implies other proteins and obviously many non coding elements. Our six proteins, therefore, can be considered as a tiny sample of the general complexity of the process, and of the informational novelty implied in the process itself.
  • d) Moreover, the process regulating neuron migration is certainly strictly integrated, with so many agents working in a coordinated way. Therefore, there is obviously a strong element of irreducible complexity implied in the whole informational novelty of the vertebrate process, an element that we can only barely envisage, because we still understand too little.
  • e) The neuron regulation process, of course, is only a part of the informational novelty implied in vertebrates, a small sample of a much more complex reality. For example, there is a lot of similar novelty implied in the workings of the immune system, of the cytokine signaling system, and so on.
  • f) The jump described here is really a jump: there is no trace of intermediate forms which can explain that jump in all existing pre-vertebrates. Of course, neo darwinists can always dream of lost intermediates in extinct species. This is a free world.
  • g) Are these 6000+ bits of functional information really functional? Yes, they are. Why? because they have been conserved for more than 400 million years. Remember, the transition we have considered happens between the first chordates and cartilaginous fish, and it can be traced to that range of time. And those 6000+ bits are bits of homology between cartilaginous fish and humans.
  • h) How much is 6000 bits of functional information? It is really a lot! Remember, Dembski’s Universal Probability Bound, taking in consideration the whole reasonable probabilistic resource of our whole universe from the Big Bang to now, is just 500 bits. 6000 bits correspond to a search space of 2^6000, IOWs about 10^2000, a number so big that we cannot even begin to visualize it. It’s good to remind ourselves, from time to time, that we are dealing with exponential values.
  • i) How great is the probability that 6000 bits of functional information can be generated in a window time of less than 100 million years, by some unguided process of RV + NS in six objects connected in an irreducibly complex system, even if RV were really helped by some NS in intermediates of which there is no trace? The answer is simple: practically non existent.
  • j) Therefore, the tiny sample of six proteins that we have considered here, which is only a small part of a much bigger scenario, points with extreme strength to a definite design inference:

The transition to vertebrates was a highly engineered process. The necessary functional information was added by design.

 

Comments
Typical nonsense coming from Rumraket. What is the probability that after having thoroughly shuffled a deck of cards the cards will appear in the exact same order they were in before they were shuffled? If you actually saw them appear in the exact same order with your own eyes, would you believe you had witnessed a miracle or would you believe you had somehow been deceived? If you actually saw them appear in the exact same order with your own eyes and denied the evidence of your own eyes would you be self-deceived, or would you blame your lying eyes?Mung
July 30, 2016
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Dionisio: "Now we’re ahead!" OK, let's enjoy our moment of glory! :) It will probably not last very much, like all good (and bad) things in this world...gpuccio
July 30, 2016
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Dionisio: What I am really happy of is that the debate has revealed many interesting aspects which were not obvious at first sight, as it always happens when people discuss with a minimum of intelligence and respect. Yes, I am very happy of that. Even if I had to witness a revival of the deck of cards argument (in dice form), which has always specially irritated me, and to pick up again the never ending story of Keefe and Szostak!gpuccio
July 30, 2016
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Update: The scores have changed: Us – them: 233 – 229. Now we're ahead! :) BTW, this "us - them" thing reminds me of an old song by Pink Floyd in their "Dark side of the moon" album. :)Dionisio
July 30, 2016
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bill: By the way, have you seen my posts 221 and 222? This technique of Deep mutational scanning seems a very good way to explore protein space. It is a high throughput technique, and it seems very powerful. Maybe we will soon have the answers we are waiting. Maybe all the functions expected by our hopeful neo darwinist friends will be found! :) And it's good to see that someone is using a metrics based on evolutionary conservation in scientific papers, comparing it to the results of another metrics. Maybe they are crypto-creationists, after all?gpuccio
July 30, 2016
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gpuccio @220
Us – them: 219 – 229. It’s a beautiful match! :)
Oh, no, we're still behind... Let's encourage more UD folks to post comments in this thread so this OP can win the match! :) Jokes aside, obviously your OP has won the debate already, since your politely-dissenting interlocutors haven't produced any serious argument against the central message of your OP. :) Actually some of them look as though they have not understood your OP yet. But let's hope eventually they will get it. Just don't hold your breath while waiting for that to happen. :)Dionisio
July 30, 2016
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bill cole at #227: I agree with you, except when you say: "If we assume that Szostak’s numbers are correct" No. I cannot even assume that. They are not correct, period. The sequence which was in the initial library, the only one about which they should be saying anything and giving numbers, was simply some sequence with a weak affinity for ATP. I think we can find some sequence with a weak affinity for anything, in a modestly big library like that. So, what did they do? Didi they just study the sequence which was in the library, and say: Hey, we can find this kind of sequence once in 10^11? No. Why? Because nobody would have cared. That sequence is simply insignificant. So, they did change it. By rounds of intelligent selection. But that means that the final result is not what can be found in a random library. The final result is what intelligent protein engineering (and not natural selection) can derive from a random library. This is the only honest way of putting it. The numbers are wrong, and completely non pertinent to any discussion about evolution. They cannot be used in any way to antagonize other numbers, like Axe's. Because they are wholly non pertinent. I agree with all the rest that you say. I can only start to think what the numbers would be for astrotactin 2, if someone were fool enough to try to derive it, or a functional equivalent, from a random library. Without any protein engineering, of course.gpuccio
July 30, 2016
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bill cole at #228: Rumracket is beyond hope. I would suggest that you don't waste your time with him. The "deck of cards" argument is probably the most stupid and irritating statement ever made by neo darwinists (not all of them, luckily, I suppose that the more intelligent ones, or those who simply are familiar with statistics, understand what it is, and strictly avoid to comment). The deck of card argument goes more or less so: 1) If we shuffle a deck of cards, each single permutation is highly improbable. True. The probability of each permutation is 1:52!, that is about 1:8*10^67. 2) Therefore, IDists could say that each result is a miracle! Wrong. Only the fools who make the deck of cards argument can think so. Each result, after having happened, has happened, There is no more any problem of probability of a result which is already there. Now, where is the problem? The problem is simply in how we define the probability of a set of results. So, a specific result, defined in advance, is completely unlikely. The repetition of a specific result, already observed, is completely unlikely. The occurrence of a specific ordered result, like all the cards in ordered sequence, is completely unlikely. So, what kind of result is very likely? It's simple: the occurrence of some sequence which has no specific order, and is not defined in any special way independently from the observation of the sequence itself after it has occurred. Indeed, that's what happens. We obtain a disordered sequence. We never, never obtain a completely ordered sequence. For the same reason that the molecules of a gas never stay in the right half of the container. Now, the ordered sequence has a probability of 1:8*10^67. It will never happen. But a generic, disordered sequence has a probability of almost 1. If Rumracket had to bet his own money, what do you think he would do? Of course, here he is only betting his intellectual dignity, and so it's easy to make the wrong choice.gpuccio
July 30, 2016
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Mung: Always a pleasure to hear from you. :) It seems interesting. I will look at it as soon as possible.gpuccio
July 30, 2016
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Gpuccio per Rumracket
“It’s like rolling 100 dice and then calculating the odds of that particular arrangement coming up. It will be 1 in 6^100. So an event with a probabiliy of 6^-100 just happened. So every roll of 100 dice is a miracle, or what? ” he says.
My question.
Rumraket July 30, 2016 at 9:07 pm colewd: If we roll the dice and a very improbable outcome came up 10 times in a row, at the time we observed it the probability of the out come is indeed 100%. The next question might be, what is the chance the result we are observing is the result of a stochastic process?
His answer :-)
What is the probability of another sequence of 10 particular but dissimilar rolls, coming up? The same as 10 of the same in a row.
bill cole
July 30, 2016
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gpuccio
As expected, my comments about Keefe and Szostak have evoked a chorus of complaints at TSZ! I should have known. Never criticize sacred monsters with skeptics! :)
I think you are addressing the fundamental argument in evolutionary biology today. If we assume that Szostak's numbers are correct we still have still have to look at additional functions of evolved proteins. My research is in the nuclear protein area where proteins have multiple binding sites. My argument would be that these proteins approach and even surpass Axe's numbers that are just dealing with binding penicillin. Rumraket's (Mikkel's) argument is that a protein does not need to bind to anything specific when it evolves so the odds are closer to Szostak's numbers. I think he may be right for the first protein of the flagellum but protein 2 thru 40 then approach Axe's numbers because they now have to bind to specific proteins inside the cell.bill cole
July 30, 2016
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hi gpuccio, There is an article at ENV that you may find interesting and of some relevance to vertebrate origins. In Current Biology, Thibaut Brunet and Detlev Arendt appear excited about the possibility of solving the "hard problem of cartilage origins." http://www.evolutionnews.org/2016/07/miracles_in_evo103032.html They give no explanation for the emergence of 3 sets of genes that code for collagen. "The ancestral soxD+ soxE+ colA+ ventral mesentery is assumed to have given rise to both the chordate sclerotome and the chelicerate endosternite," they say, 'assuming' that six transcription factor genes and the collagenase gene conspired to create the first hard parts.Mung
July 30, 2016
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As expected, my comments about Keefe and Szostak have evoked a chorus of complaints at TSZ! I should have known. Never criticize sacred monsters with skeptics! :) I have discussed Keefe and Szostak's paper ad nauseam. I cannot always repeat the same things. Very briefly. The lies are those about what that paper means. The paper only shows that in a big enough random library of proteins there are a few molecules with some weak binding of ATP. And that it is possible to select those molecule in the lab, by artificial selection, and to use a procedure of rounds of mutation and further selection for ATP binding, and guess what? They obtain a molecule which strongly binds ATP. And which has some folding. And which is absolutely non naturally selectable,, exactly like its precursors in the original library! Amazing! So, protein engineering works (up to a point). Who would have suspected such a thing. Important points: 1) Neither the weakly binding proteins, nor the artificially engineered final protein, have been shown to be even vaguely naturally selectable, Indeed, the final protein has been shown to be deleterious, in the right environment. 2) Some folding has been shown for the engineered protein, not for the "natural" sequences in the original library. 3) You can like the paper as you want, but it is a fact that it tells absolutely nothing about the occurrence of naturally selectable protein sequences in random libraries. Least of all quantifies it.gpuccio
July 30, 2016
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Allan Miller at TSZ:
It is clearly an observed fact that many folds are not obviously related to other folds within extant life. This, however, does not prove them isolated islands of function in itself. Because if evolution and common descent were true, one would expect loss of relationship information over time. In an evolutionary scenario, many configurations are passed through then lost. It is wrong – the same mistake as Durston’s – to regard extant life as a representative sample of all sequence space. It is also wrong to regard the lack of detectable ‘lateral’ connection to be conclusive of a lack of coalescent connection when adding the dimension of lineage. It seems to be a molecular version of the ‘dogs giving birth to cats’ trope – you can’t get to modern sequence A from modern sequence B.
My rather clear question was: "Maybe Alan Fox thinks that there are a lot of completely different sequences, with a near constant distribution across sequence space (whatever that means), which could easily work in ATP synthase in the place of the alpha and beta chain. But why should that be true? Has he any reason to believe such a weird thing, beyond simple imagination?" Allan Miller's response can represent a clear answer: none. Allan, must I remind you that those "configurations" which "are passed through then lost" must be. to be of any relevance, increasingly functional configurations? You see, we are again at the myth of lost intermediates. So, I ask to you, too: Have you any reason to believe such a weird thing, beyond simple imagination? And beyond your dogmas?gpuccio
July 30, 2016
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Rumraket, at TSZ, goes wild with the old "deck of cards" idiocy. "The posterior probability fallacy is the quintessential fallacy of creationism." he says. "It’s like rolling 100 dice and then calculating the odds of that particular arrangement coming up. It will be 1 in 6^100. So an event with a probabiliy of 6^-100 just happened. So every roll of 100 dice is a miracle, or what? " he says. He has really understood everything! So, I suppose that we can easily observe the molecules in a gas assuming ordered states, like for example being all in the right half of some volume at the same time. Of course, it is perfectly possible! After all, the probabilities of that configuration are exactly the same as those of any other configuration which is commonly observed! Only stupid creationists could believe that the laws of probabilistic mechanics, as applied to gases, have any value!gpuccio
July 30, 2016
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bill: I have looked at a couple of other papers using Deep mutational scanning . The idea is the same: mutations are either deleterious or neutral, usually with some bimodal distribution. Interestingly, there is good correlation between evolutionary conservation and experimental fitness results, but with distinct differences. Obviously, conservation is an "experiment of nature", and lab conditions are not really the same thing as natural conservation. However, both metrics are measuring the same thing (functional restraints), with different methodology. The strong similarity of the results is important. But also the differences can reveal important aspects of protein function specificity, as suggested by the authors in their final remarks.gpuccio
July 30, 2016
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bill: This is very interesting: "Deep mutational scanning of an RRM domain of the Saccharomyces cerevisiae poly(A)-binding protein" http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3851721/ Just a couple of quotes (the paper is rather complex, and really rich of facts):
While the enrichment scores of the single amino acid substitutions indicate that most mutations were deleterious for RRM2 function, a few mutations had enrichment scores that were greater than that of the wild type. In particular, the enrichment score for Q194C was 2.9. However, we measured the growth rate of yeast cells carrying Q194C and found that it was the same as those carrying the wild-type version (data not shown). This observation agrees with our finding that enriched variants follow the distribution of synonymous mutants and therefore are likely to be neutral
And:
By assaying variants of the RRM2 domain of the yeast Pab1 in high throughput, we scored most (83%) of the possible 1500 single amino acid substitutions (including stop codons), and more than 100,000 variants with multiple substitution events, in a 75-residue-long sequence. The results highlight the RNA-binding surface of RRM2 as the most important element for its function, although each position in the RRM2 shows a nearly unique pattern of mutational sensitivity. We clustered the data to reveal other residues highly sensitive to mutation, as well as core hydrophobic residues that tolerated substitution only by other hydrophobic amino acids. By comparing the evolutionary conservation of RRM residues with their ability to function in the context of the yeast Pab1 protein, we could implicate some residues in yeast-specific functions. Finally, we used epistasis analysis to identify interacting residues in Pab1.
This techinque of Deep mutational scanning seems specially appropriate to study the protein functional space.gpuccio
July 30, 2016
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Dionisio: Us - them: 219 - 229. It's a beautiful match! :)gpuccio
July 30, 2016
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Are we closer to match the number of posts related to this OP in the other blog? :)Dionisio
July 30, 2016
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gpuccio @216 Yes, it was picturesque, like RV at its best. But it could affect the sequence functionality (i.e. the statement meaning), specially in the cases of folks who tend to misinterpret -sometimes apparently intentionally- most of what you write so clearly. The mind is so amazing that it automatically corrects those misspelled words for us to understand the whole context. But if some folks have a priori decided not to understand your point, they could use any misspelling as a cheap excuse to justify their attitude. :)Dionisio
July 30, 2016
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Dionisio at #214: I did not know that one, seems interesting. I will take the time to read it carefully, thank you.gpuccio
July 30, 2016
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Dionisio #212: Corrected! But "Why son’t we ass" was picturesque, wasn'it? RV at its best! :)gpuccio
July 30, 2016
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bill: By the way, another "small" point about those numbers (be them Keefe & Szostak's, Axe's, or Ayashi's: right or wrong that they may be, they are all about rather "short" protein sequences, about 100 AAs. Astrotactin 2 is a 1339 AAs protein. 889 of them are identical in sharks and humans.The positives are 1048. I would really appreciate if our friends at TSZ could comment about this very simple fact.gpuccio
July 30, 2016
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Hierarchy and extremes in selections from pools of randomized proteins. Boyer S1, Biswas D1, Kumar Soshee A1, Scaramozzino N1, Nizak C2, Rivoire O3. Proc Natl Acad Sci U S A. 2016 Mar 29;113(13):3482-7. doi: 10.1073/pnas.1517813113. Epub 2016 Mar 11.Dionisio
July 30, 2016
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gpuccio @205
By the way, have you noticed that the total functional information content of the beta chain of ATP synthase as conserved from E. coli to humans (about 6oo bits), while huge and amazing, is still much lower than the mean functional information jump of the six proteins in my OP?
Interesting observation indeed.Dionisio
July 30, 2016
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@205 "Why son’t we ass the 10^70 starting sequences computed to be necessary to get the wildtype sequence in the rugged landscape paper?"Dionisio
July 30, 2016
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gpuccio @209
There are more comment about my OP in the TSZ thread (223) than here [...]
Wow! they like you there too! Have you considered running for a public office in the next elections? Maybe UN General Secretary? :)Dionisio
July 30, 2016
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gpuccio @205
[...] they are still using that paper for their propaganda. They are shameless!
In terms of biology research these days that paper is kind of old (2001?), isn't it? Can't they pull out something newer? They need more fresh food for thoughts. Biology research* is very dynamic in the sense that 'surprising' and 'unexpected' discoveries are happening almost daily these days. The old dogmas** are being shaken by some of those discoveries. Over 15-year old publication in biology seems outdated, doesn't it? (*)There are certain fields of knowledge where the old documents remain as valid as they were at the time they were written originally, because what they say does not change with time, although people's interpretation may change daily. (**) http://plato.stanford.edu/entries/information-biological/ http://arxiv.org/abs/1606.07184v1Dionisio
July 30, 2016
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Just a little oddity: There are more comment about my OP in the TSZ thread (223) than here (209 including this one). I suppose I must really be thankful to my "friends" there for the kind attention! :)gpuccio
July 30, 2016
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bill: By the way, at present my favourite option for the origin of de novo genes is: design of pre-existing non coding sequences by guided transposon activity.gpuccio
July 30, 2016
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