Junk DNA turns out to have function again

Joe, Regarding your criticism of Zachriel's statement,

No, but the Theory of Evolution makes many confirmed predictions…

realize that the confirmation comes before the prediction, which is made in retrospect. This makes the predictions a lot more reliable! So, for example, the presence of junk DNA is currently interpreted as evidence for Darwinian evolution, while the absence of junk DNA will also eventually be shown as evidence of evolution. Same with ring species. Pretty slick! -Q Querius

Rocinante: "Please reference this alleged theory of evolution so we can all see what it predicts." For a theory that doesn't exist, UD (and yourself) seem to spend a lot of time and effort attacking it. Keep tilting at those windmills. lack of Focus

Zachriel is bluffing again:

No, but the Theory of Evolution makes many confirmed predictions...

Please reference this alleged theory of evolution so we can all see what it predicts. Our bet is Zachriel won't do so because it cannot. Sweet... Joe

DNA Joke- There isn't any evidence for a chaperone-free organism. Your imagination and wishful thinking are just that. However we all know that your position requires a chaperone-free organism to have existed so we understand your desperation. Joe

Dr JDD: It {chaperones} does not support evolution however in and of itself. No. That can only be supported by a consilience of the evidence. Dr JDD: In support of evolution we can propose that cells and replicators pre-cursor to what we observe now existed and reproduced without chaperones, and you can rationalise that they have been lost through evolution over time but the observations that all life require chaperones in and of itself is of no evidence to support evolution: that is the crux. No, but the Theory of Evolution makes many confirmed predictions, with strong support for mechanisms of complex adaptation, so it is reasonable to hypothesize a similar process for the origin of primordial cellular mechanisms. In particular, some proteins fold without a chaperone, while extant chaperones give indication of having evolved in families. Finally, there's always going to be gaps, especially in the early history of life. That hardly implies that evolution isn't the best explanation. Zachriel

I was not trying to mock you JDD, just offering up an analogy, in the hope that it would help you see how you are misconstruing my position

  OK, how about we accept we have both misconstrued each other’s positions (because I believe you are also misconstruing mine)? I will admit given my repetitive discussions with materialists about such subjects, they usually will say that such and such DID or MUST HAVE happened. I can perfectly accept MAY have or is an alternative theory within the confines of this discussion (not even worrying about how you get to evolve a complex protein like a chaperone in the first place). The thrust of my argument – and my position with many materialists is that regardless of whether you can test it or not, you can observe, much like materialists maintain that something has a likelihood of design, and that is a valid theory. Just as valid as abiogenesis and just as valid as the multiverse, both of which (among many other things) are considered “scientific” theories. The problem I come back to here is how most materialists will say that those theories are fine to make (despite you not really being able to test them) but design as a theory is not. That is inconsistent and hypocritical and led through necessity by a world-view.   So you must understand my position here – I am not saying chaperones are proof of design. I am saying this is a piece of evidence that can support design. It does not support evolution however in and of itself. In support of evolution we can propose that cells and replicators pre-cursor to what we observe now existed and reproduced without chaperones, and you can rationalise that they have been lost through evolution over time but the observations that all life require chaperones in and of itself is of no evidence to support evolution: that is the crux. So if new evidence emerges, i.e. that a cell/replicating organism can exist with the pre-cursor components (proteinacious components from a genetic material) but without chaperones, then this “evidence” suddenly as you say, swings away from support of design, as we know it could potentially happen without design.   This is something that virtually all materialist proponents I have encountered will not accept nor entertain. I’m not asking you/them to accept the evidence and change opinion; I am merely trying to establish it can be viewed as supportive evidence for design. (And I am incidentally not writing any of this in the vain hope that I might convince you or change your opinion – but rather for the observer who wants to hear both sides and make an informed decision without complete bias).  

Okay, I want you to really pay attention here, this is important: DNA would have demonstrated the possibility of starter-less cars. Has he proved that JDD was wrong to suppose that a starter deity created starter motors ex nihilo? No, he has not. Has he demonstrated that JDD’s argument “No starter-less cars today, therefore no starter-less cars ever” is fallacious. Yes, he has. It still remains possible that starter motors were created by a deity.

  You see I actually agree with you here and always have. Being able to experimentally make a starterless car would in fact swing this particular set of evidence in the balance of DNA over JDD. Of course, I have no problem with that.  

Okay, if you really need me to spell it out: from the assertion that replicators can exist without chaperones, I predict that we will be able to produce, at some future date, a replicator that replicates without chaperones. Kinda obvious, y’think?

  Well done. Sometimes you need to ask stupid questions otherwise conversations get side-tracked. Of course it is obvious. Have we done this yet? As you say, no. So my next question: What time-frame would one accept this experiment to take? What constitutes failure? 10 years? Your life-time? 1000 years? How do you know when to stop trying and that it will not be possible? After how many attempts does the alternative hypothesis (design) become more feasible? What is the null hypothesis for this experiment?  

Dichotomous thinking is a particularly popular failing amongst IDists…

  Actually, one IDist could cite the infamous idiom in relation to a materialist here: Pot, kettle, black. I could cite several examples but perhaps best to agree to disagree as this would side-track completely. I should say though that many IDists accept a lot of evolutionary principles and thinking – just not on the extrapolated and grand scale that is portrayed with virtually infinite time alluded to allow for such changes.  

You keep thinking I am making a positive claim that chaperone-less replicators did exist. I am merely pointing out your fallacy : “if X today, then X always” I fail to see the circularity in my position

  Again, please understand, I am NOT saying “If X today, then X always.” You are also misunderstanding me. I am saying all we currently can observe is X today. Now that does not necessarily MEAN X always, but with no other evidence to support X did not exist before (and given X’s vital role in ALL life as we know it), it provides a level of evidence that X may be necessary for cellular life. If that is the case (i.e. that it is necessary), it poses a problem for abiogenesis and the materialistic worldview. I am certainly not saying because “X today” this disproves abiogenesis or the materialistic account. It is a piece of evidence to consider, and the idea is that the vast majority of materialists will never acknowledge this point – they will assume and vehemently defend the notion that a cell/replicator must, nay did exist that had no “X” present.   This is where the circular argument comes in – namely, that people will argue that it is not a valid point that chaperones are needed todayfor many proteins to correctly fold because once chaperones evolved, other proteins evolved alongside them. That is a circular argument because it assumes that proteins that require aid in folding must not have existed pre-chaperone and they are only the result of post-chaperone era, which is an unproven assumption. Again, that is not me saying they definitely did not exist, I am just balancing what we can observe and what experiments to address this have so far shown (or failed to show). Dr JDD

DATCG writes:

Chaperones were important from the beginning of time. Not just for “modern cells.”

Here, Ladies and Gentlemen, we see the fallacy in its distilled form. JDD and I were discussing pre-LUCA/peri-LUCA evolution, and along comes DATCG touting the ubiquity of chaperones in the cyanobacteria that we observe today, that is, modern cyanobacteria. DATCG is unable to wrap his brain around the idea that cyanobacteria may have descended from an ancestor that lacked chaperones. Oh dear. DNA_Jock

Joe #82

That’s just stupid. If that were true then all deaths would be considered murders, all fires would be arsons and all rocks would be artifacts. You must be proud of your ignorance…

Consistent with design does not mean designed of course. The idea being that you could look at a death which seems pretty clearly to be from natural causes and still inferred it was designed. You may have a good reason for doing so: a particularly strong motive or a data point that just doesn't quite fit. This is the stuff of classic mystery stories. But you might just say: it could have been designed to look natural, we cannot discern the designer's motives. Jerad

DNA_jock said... "We agree that chaperones help proteins fold faster, and that this is important in the cell. The modern cell." A 2014 paper discusses role of chaperones in cyanobacteria... Cyanobacterial heat-shock response: role and regulation of molecular chaperones.

Sustained long-term exposure to changing environmental conditions, during their three billion years of evolution, has presumably led to their adaptation to diverse ecological niches.

Cyanobacteria exist everywhere on earth. Very diverse on land, in sea and fresh water. From very hot, dry climates to moist, or cold. From the North Pole to the Sonoran Desert.

The ability to maintain protein conformational homeostasis (folding-misfolding-refolding or aggregation-degradation) by molecular chaperones holds the key to the stress adaptability of cyanobacteria."

Chaperones were important from the beginning of time. Not just for "modern cells." DATCG

DNA Joke:

I am always happy to acknowledge that anything is consistent with a design inference, because anything is consistent with a design inference.

That's just stupid. If that were true then all deaths would be considered murders, all fires would be arsons and all rocks would be artifacts. You must be proud of your ignorance... Joe

JDD writes:

DNA_jock, I’m not too bothered by the mocking, but I would prefer that you did not conflate and inflate my words into something they are not saying. I have not said what you are implying, namely that because we do not see cells/replicators around or have history of them without chaperones that they did not or could not have existed…

I was not trying to mock you JDD, just offering up an analogy, in the hope that it would help you see how you are misconstruing my position. I even provided post numbers so that you could follow the analogy through our conversation. JDD has questions:

1) Could an alien visiting the earth try to create a working car without a starter motor? Do you think they could, with all the parts of cars available to them currently around in the whole world today? If they could, who would win that argument?

Yes, I think they could, but it might take a lot of work. “If they could, who would win that argument?” Okay, I want you to really pay attention here, this is important: DNA would have demonstrated the possibility of starter-less cars. Has he proved that JDD was wrong to suppose that a starter deity created starter motors ex nihilo? No, he has not. Has he demonstrated that JDD’s argument “No starter-less cars today, therefore no starter-less cars ever” is fallacious. Yes, he has. It still remains possible that starter motors were created by a deity.

2) So what testable predictions can we make from asserting that cellular life can exist (survive, replicate) without the presence of chaperones? (I repeat this because you did not answer it – you confuse my question with the thought that I have no ideas of the answers myself – far from it, but I want to hear how you would answer it, as a materialist)

Let’s be clear about the context here: you asked this question in response to my claim @72 that my position differed from the “design inference” because my position entailed testable predictions. My incredulity is my response to your asking such a mind-blowingly dumb question, as in “Really? Nothing comes to mind?” [emphasis in original] Okay, if you really need me to spell it out: from the assertion that replicators can exist without chaperones, I predict that we will be able to produce, at some future date, a replicator that replicates without chaperones. Kinda obvious, y'think?

3) What evidence would it take for you to come to a conclusion that cellular life cannot function without chaperones?

That’s a tough one I agree, and gets us into some of the definitional challenges. Challenge (1) are we restricting “chaperones” to those that consume ATP, or are we expanding the definition to include any proteins that have a modest anti-aggregation effect (such as serum albumin)? Challenge (2) the term “cellular life”: if (as I suspect) researchers are able to create a replicator that lacks “chaperones”, but they fail repeatedly to create “cellular life” and they demonstrate that they are failing because a specific, essential category of membrane protein cannot be synthesized without chaperones, then I would say that a pretty good case had been made. I think a large part of the problem is with labels that human beings feel compelled to put on things. Dichotomous thinking is a particularly popular failing amongst IDists...

I know you are committed to your materialism and the likely answer is observation of a designer or “miracle” that could be reproduced and tested, but let us play another little scenario game:

I love disappointing IDists.

Imagine that you visited another planet that had water but no life. It had the right environment to support life but life had not evolved. Now let us also assume that evolution can progress from a single celled organism to intelligent conscious beings such as humans (big assumption!). As we have the capacity to travel such distances, we had also reached a point in science where we understood the genome fully and knew a lot of DNA/RNA, protein, carbohydrate, lipid etc functionality.So much so that we designed ourselves a replicating cellular organism, one that evolution on our earth had not produced. We planted this on the distant planet, to let evolution take its course. Let’s say then 2 billion years later on that planet very intelligent life has evolved and is present. Scientists keen to understand their origins trace through fossil records and DNA evidence and archeology that they believed we evolved from a single celled organism. They have no evidence that anyone ever landed on their planet, they have not contacted any extra-terrestrial life, they think they are alone in the universe. Tell me, what evidence could they use to ascertain or differentiate between some intelligent life planting a bacteria on their planet 2bya versus abiogenesis? The fact is with this scenario, someone intelligent did plant it. But I am curious how you think you could distinguish that from it arising itself?

Francis Crick is a pretty smart guy (James Watson not so much). But, that jackass Dawkins was correct that this would just move the problem of abiogenesis back one step to a different world. And the Nixon-speech writer who did the ambush interview was too dumb to realize the point. To answer your hoary old chestnut of a question, it would be very difficult to distinguish between the possibilities; absent any data one way or the other, we invoke William of Ockham (post 66), and opt, provisionally, for the explanation with one fewer explanatory entities.

YET, as with most materialists, you refuse to acknowledge this is consistent with a design inference and by default use a circular argument to justify why modern cells require chaperones.

You keep thinking I am making a positive claim that chaperone-less replicators did exist. I am merely pointing out your fallacy : “if X today, then X always” I fail to see the circularity in my position. What on earth makes you think that I “refuse to acknowledge this is consistent with a design inference”? I am always happy to acknowledge that anything is consistent with a design inference, because anything is consistent with a design inference. That’s what makes it not science. DNA_Jock

DNA_jock, I'm not too bothered by the mocking, but I would prefer that you did not conflate and inflate my words into something they are not saying. I have not said what you are implying, namely that because we do not see cells/replicators around or have history of them without chaperones that they did not or could not have existed. I also did not say that is proof they were designed. What I am arguing is based on the given evidence one cannot definitively distinguish between design and evolution here (as with much in evolutionary biology frankly) and if anything, it adds some evidence to support the possibility of design. YET, as with most materialists, you refuse to acknowledge this is consistent with a design inference and by default use a circular argument to justify why modern cells require chaperones. Now if you can produce some record of pre-chaperone life or reproduce some experiments that show replicators/cells can exist with the production of proteins but not chaperones than you have stronger evidence that this is a favourable theory (in this specific example) over a design. Some questions for you: 1) Could an alien visiting the earth try to create a working car without a starter motor? Do you think they could, with all the parts of cars available to them currently around in the whole world today? If they could, who would win that argument? 2) So what testable predictions can we make from asserting that cellular life can exist (survive, replicate) without the presence of chaperones? (I repeat this because you did not answer it - you confuse my question with the thought that I have no ideas of the answers myself - far from it, but I want to hear how you would answer it, as a materialist) 3) What evidence would it take for you to come to a conclusion that cellular life cannot function without chaperones? I know you are committed to your materialism and the likely answer is observation of a designer or "miracle" that could be reproduced and tested, but let us play another little scenario game: Imagine that you visited another planet that had water but no life. It had the right environment to support life but life had not evolved. Now let us also assume that evolution can progress from a single celled organism to intelligent conscious beings such as humans (big assumption!). As we have the capacity to travel such distances, we had also reached a point in science where we understood the genome fully and knew a lot of DNA/RNA, protein, carbohydrate, lipid etc functionality.So much so that we designed ourselves a replicating cellular organism, one that evolution on our earth had not produced. We planted this on the distant planet, to let evolution take its course. Let's say then 2 billion years later on that planet very intelligent life has evolved and is present. Scientists keen to understand their origins trace through fossil records and DNA evidence and archeology that they believed we evolved from a single celled organism. They have no evidence that anyone ever landed on their planet, they have not contacted any extra-terrestrial life, they think they are alone in the universe. Tell me, what evidence could they use to ascertain or differentiate between some intelligent life planting a bacteria on their planet 2bya versus abiogenesis? The fact is with this scenario, someone intelligent did plant it. But I am curious how you think you could distinguish that from it arising itself? Dr JDD

Earth to DNA Joke- unguided evolution doesn't have any predictions and its entailments are: change, stasis, disease and deformities. Joe

Z:

There is evidence that eukaryotes evolved from simpler cells.

No, there isn't any such evidence, only a need.

There is evidence that life didn’t always exist on Earth, but started in simple form soon (in millions of years) after liquid water formed.

Wrong again- you conflate a need with evidence. Joe

Some time later: JDD "Did you know that starter motors are delivered to car factories by vehicles that have starter motors? The inference to best explanation is that there exists a starter motor deity that created starter motors." DNA "Oh Cthulhu! You have got to be kidding me." DNA_Jock

What the heck, I'll try an analogy, imperfect as they are. Two aliens, JDD and DNA, arrive on earth, unaware of the history of the internal combustion engine. JDD (59) “Given that all cars have starter motors, what evidence do you have that cars could exist without starter motors?” DNA (60) “Well, as you yourself put it, plenty of internal combustion engines do not require starter motors. It seems to be a common Centaurian fallacy that ‘just because X is essential today, X was always essential’” JDD (62) “You`re confusing science with fantasy. Although snow blowers, lawn mowers, chain saws and outboard engines do not need starter motors, all cars do. You say it is a common Centaurian fallacy to say that just because things are this way now means they couldn’t have been differently before but it is an equal fallacy to say they must have been different before otherwise they do not fit in with your worldview. I certainly would not argue with the sentiment that things we see now are probably much different to a long time ago, but if you actually take that argument for what it is and extend your own argument, you suddenly support YECs who will say that perhaps radioactive isotopes had different decay rates in the past hence the apparent very old ages. After all, just because something appears a certain way/rate now does not mean it always was!” DNA (66) “We agree that most internal combustion engines do not require starters, we agree that things we see now are probably much different to a long time ago. We agree that modern cars have starter motors. But earlier cars could have been much worse. If better cars came along they would replace the crummy cars. Centaurians fail to appreciate the importance of this fact.” JDD (70) "Not at all. I and many fellow Centaurians completely understand this argument and the importance of it. But we do not observe anywhere any cars without starter motors" DNA (72) "Say what? You just did it again!" JDD (73) “Oh I understand the concept, I just don't accept it. You are arguing thus: 1) All cars have starter motors. 2) Therefore there must have been a time when cars did not have starter motors and could get by without. What testable predictions can we make from asserting that cars could exist that lacked starter motors? ” DNA "Really? DNA_Jock

Dr JDD, Try reading what I actually wrote, rather than what you think I wrote. Specifically, the words "could" and "importance" in the passage in question. Your strawman is showing:

1) We see all organisms with protein class X present and necessry for life 2) Therefore there must However, there may have been a time when cellular organisms replicators did not have protein class X and could survive without

Similarly:

So what testable predictions can we make from asserting that cellular life can exist (survive, replicate) without the presence of chaperones?:

Really? Nothing comes to mind? Contrast that with

The design inference predicts there are complex ordering to the molecular level of the cell that are not observed to spontaneously come into existence yet are necessary to life.

As written, it isn't a prediction. Critically, it is not an entailment. Rather it is a time-qualified observation which happens to be the primary motivation for ID. Primary outside of theology, that is. DNA_Jock

Dr JDD: 1) We see all organisms with protein class X present and necessry for life 2) Therefore there must have been a time when cellular organisms did not have protein class X and could survive without What evolutionary biologists see is evidence that complex adaptations have evolved over the history of life, both on the molecular and morphological levels. There is evidence that eukaryotes evolved from simpler cells. There is evidence that life didn't always exist on Earth, but started in simple form soon (in millions of years) after liquid water formed. There is molecular evidence that extant cellular processes evolved from simpler processes. The evidence from the other end is more tenuous. We have nucleic acids that can self-catalyze. We observe lipids forming into micelles that can grow and divide. Zachriel

Substrate x is converted to substrate y in a system where you can only detect enzyme A. What can you scientifically say about that observation? Can you say "enzyme A requires a co-factor for catalysing y-->x" ? That is analagous to saying "we do not observe something therefore we have no experimental or direct evidence for it" which is what science works on, not extrapolations or speculations.

You say “Not at all”, but you cannot even finish the paragraph without repeating the error. Dammit, I need a new meter.

Sorry but you really do not get this do you. You are equating the understanding of a concept/idea with the acceptance. You are saying because I do not accept your concept in this particular case I have made an error and/or do not understand your point. That is a completely ludicrous way to view theories and is self-validating therefore is non-falsifiable. You can understand Freud's theories completely. You can even accept 90% of them. But just because you reject some of his theories on psychology does not mean you do not understand them. How in the world is this science? Can anyone help me??: 1) We see all organisms with protein class X present and necessry for life 2) Therefore there must have been a time when cellular organisms did not have protein class X and could survive without If you take out the assumptions of abiogenesis and a materialists worldview that is what your argument here boils down to. So what testable predictions can we make from asserting that cellular life can exist (survive, replicate) without the presence of chaperones? The design inference predicts there are complex ordering to the molecular level of the cell that are not observed to spontaneously come into existence yet are necessary to life. Tell me, have you or anyone else ever observed directly the coming into existence through random processes of chaperones? Tell me how the design inference has failed to predict such complexity? What would you expect from a design based cell? Dr JDD

Early replicators could have been horrendously inefficient and extremely slow (to fold their proteins, for instance), but if there were able to propagate better than their lame-ass cousins, they would do just fine. Every single ID proponent that I have read fails to appreciate the importance of this fact.

Not at all. I and MANY other ID proponents completely understand this argument and the importance of it...We do not observe anywhere horribly inefficient cellular organisms...

You say "Not at all", but you cannot even finish the paragraph without repeating the error. Dammit, I need a new meter. You ask:

How is this any different or more “scientific” than the design inference?

Because it entails testable predictions, unlike the "design inference" which does not, pace Wells. DNA_Jock

Joe @64: Sorry, I do not know if this is why genetic engineering has failed as such. In the industry I am in it is certainly known that drugs and products can and will fail due to simple folding problems or modification problems, stability, aggregation, etc, etc. Many factors influence this and you can have the best biologic in the world but if it is not "druggable" then there is no point. And this is in a highly controlled and externally manipulated environment. Dr JDD

DNA_Jock,

You are arguing that, based on the 20 – 30% of extant proteins that do require chaperones, a rudimentary protein synthesizing organism would absolutely require chaperones. It just doesn`t follow

No I am not arguing that at all, not exclusively as you put it. Where did I write that? You are putting words in my mouth. My conclusion from that line of reasoning was: we could assume at best case 10% of cytosolic proteins require chaperones, etc. that is not insignificant I am saying if 20-30% of proteins absolutely require chaperones (hypothetically as I do not know of a solid reference for this) there is a good chance some really important proteins cannot just “fold correctly”. That is observable evidence, based on what we see around us and can test and measure. What we can also test and measure is that in any organism if you rid the cell of chaperones, even archaea who have 3 I believe, it is lethal to the organism. That we can observe. Now with archaea I believe there is just 1 that is necessary, but that still makes the point either: - The simplest of cells have evolved to rely on chaperones from a pre-chaperone era where they did not rely on them for life - Cellular life cannot survive and reproduce without the aid of protein folding molecular machinery So my point is not that all life “absolutely require chaperones” (please show me where I have implicitly stated that?), my point that to make the claim that there “must have been” a pre-chaperone era is unscientific as it is not founded on evidence that is testable and observable but mere speculative fantasy. I’m with Joe @68 on this one – you are extrapolating which is a sin in science, yet most of Darwinian evolution is extrapolating in a similar way. So please do tell me, what evidence do we have that simpler cells could exist without chaperones, given that no cellular organism today can be rid of all their chaperones? How do you arrive to such a conclusion that a cell must have existed without these proteins? There are a lot of scientists who would look at such evidence as certain complex functionally specific necessary proteins present in all life, and make a different conclusion to you – that is, they may even accept UCD but from a design perspective because the machinery necessary for life is absolutely necessary and complex and therefore as we have no observable evidence of anything less complicated maintaining “life” and we know something so complicated and organised could not just spontaneously appear in such ordered fashion, this is seen as strong evidence for external tinkering as opposed to dust to molecules to molecular machines. So my point is it is fine to invoke the “mysteries of nature” just undergoing abiogenesis to a horribly inefficient route until it magically produced efficient cellular machines (and then left no trace of its predecessors) but you cannot pretend that this is any more scientific than invoking a designer. And THIS is my criticism (note, I am not saying you are 100% wrong which you fail to grasp. I am not saying this is proof of a designer) – you speak as most materialists do in “must have” and “just so story” terms. There must have been a cellular predecessor that could operate and function without such machinery, its just we have no trace of it, we never will know what it looked like, and it was lost to evolution. But it must have existed (otherwise I have to call into question my whole world view...). How is this any different or more “scientific” than the design inference? Secondly, I am certainly not saying the laws of physics have changed. I am making a principle point – the fact that the data does not fully support your position therefore you invoke an alternative explanation which cannot be proven or tested nor observed (abiogenesis and “early” cellular life) and call this scientific fact – only to support your worldview. This is just as bad (often worse) than the YEC who says the rates of radioisotope decay may have been different at “creation” than they are now.

Early replicators could have been horrendously inefficient and extremely slow (to fold their proteins, for instance), but if there were able to propagate better than their lame-ass cousins, they would do just fine. Every single ID proponent that I have read fails to appreciate the importance of this fact.

Not at all. I and MANY other ID proponents completely understand this argument and the importance of it. We just do not accept that it can account for abiogenesis and the appearance of complex molecular machineries. Especially when the basic requirements for cellular life in what we can observe involve many components efficiently balanced. We do not observe anywhere horribly inefficient cellular organisms. You claim that is because they no longer exist as they were selected out but that makes your claim non-observable therefore speculation at best and pseudoscience at worst. The only evidence you have that there were “highly inefficient cellular organisms” is because you have an a priori commitment to materialism, not because of any scientific observations or experimental evidence. And that is something I have never heard a materialist ever acknowledge in these discussions. Dr JDD

This is just a note of appreciation for those of you with informed and well-thought-out replies. Incidentally, I've learned the hard way on several occasions to compose my longer posts in an external editor and then cut-and-paste it in. -Q Querius

DNA Joke:

Early replicators could have been horrendously inefficient and extremely slow (to fold their proteins, for instance), but if there were able to propagate better than their lame-ass cousins, they would do just fine. Every single ID proponent that I have read fails to appreciate the importance of this fact.

You don't have any evidence for these alleged early replicators that were horrendously inefficient and extremely slow (to fold their proteins, for instance) . You don't have any evidence for a chaperone-free cell. You can't get from simple replicators to those which produce proteins. Every single evo proponent I have read fails to appreciate the importance of these facts. Joe

Chapter XIII "What Teaches Proteins Their Shapes?" Dr Sermonti discusses prions and how they rearrange a host protein's spatial shape just by contact. He discusses the failures of genetic engineering too. He says:

Proteins transferred from one kingdom to another through biological smuggling did, indeed, form in their new environment, but they often failed to function. The amino acids making up the proteins duly placed themselves in the proper sequence, but they failed to take up the spatial configuration necessary to make the proteins as active as they were in the donor species. Instead they formed glutinous masses, the equivalent of a dish of overcooked spaghetti. page 129

Enter chaperones... Joe

Dr JDD, You seem to be arguing against a strawman of your own construction. We agree that many extant proteins do not require molecular aides for folding (you put the proportion at 70 – 80%). You are arguing that, based on the 20 – 30% of extant proteins that do require chaperones, a rudimentary protein synthesizing organism would absolutely require chaperones. It just doesn`t follow. We agree that “things we see now are probably much different to a long time ago”, but you conflate my position with a denial of uniformitarianism - “radioactive isotopes had different decay rates in the past”. Really? There`s no reason to think that the laws of physics and chemistry have changed during life on earth, but every reason to think that the circumstances (e.g. oxygen levels, predation) have changed. We agree that chaperones help proteins fold faster, and that this is important in the cell. The modern cell. Early replicators could have been horrendously inefficient and extremely slow (to fold their proteins, for instance), but if there were able to propagate better than their lame-ass cousins, they would do just fine. Every single ID proponent that I have read fails to appreciate the importance of this fact.

So it is fine for you to have your opinion on what we cannot observe and cannot test (that a cellular organism could exist without chaperones) but it is not based upon experimental science and is assumption and deduction to fit with your world view – no different to how one might conclude there needed to be a designer as all life have proteins needed to correctly produce other proteins necessary for life.

Paging William of Ockham, William of Ockham … P.S. would you set Joe straight on his “Why is a fly not a Horse?” rubbish. He`s not going to believe me… DNA_Jock

Gpuccio asks

Again, I would appreciate examples of generic isolated alpha helices which are naturally selected because they confer a reproductive advantage in a biological system. Again, it’s your theory, not mine. You have to show the supporting facts.

At the risk of running afoul of all those qualifiers in there - “generic” “isolated” “naturally selected” “reproductive advantage” “ biological system” – I`ll offer up Ma & Ptashne PMID:3115591 Giniger & Ptashne PMID: 3317067 With the note that there’s a wrinkle, but I`ll let you figure that out for yourself…

gp: Again, homology can detect recombination.

DNAJ This is rather misleading. Yes, by looking at DNA sequences, we can detect the recent recombination of relatively large fragments. But, as I went to considerable lengths to explain to you, the absence of detectable homology DOES NOT preclude common ancestry.

Gp Why these strange limitations? The sequences in ATP syntase have remained almost the same for about 4 billion years. The Helix-loop-helix domain in human myc shows clearly detectable homology with the same domain in the mxl-3 protein in C. Elegans…

Thanks to selection; you are making my point for me. After the recombination event, selection may preserve or destroy the homology signal. Remember, your argument was that IF recombination had occurred, THEN we would certainly be able to detect it. My point was “sometimes, sometimes not”. It is you, gpuccio, who is making the claim that [protein X] has no homolog that I can detect, therefore she leapt fully formed from her father`s forehead. I, DNAJ, am merely making the observation, “it ain`t necessarily so”.

As a lot of conserved sequences or anyway of recurrent motifs, some of them very short, are well known, you can certainly show the relevant role of those sequences and motifs in building up long and complex functional proteins by recombination and natural selection

and

My point is simple. If recombination of functional modules were really a fundamental component in protein evolution, as many on your side have bben affirming, then we shopuld be able, in the general case, to recognize the functional modules which have been recombined, and therefore be able to analyze the role of recombination according to facts.

I know. Isn`t titin a great example: it`s a huge protein, and most of it is obviously the result of recombination events – in this case duplications of the Ig-domain. But as to it being the “general case” :

While it can be true that in some cases we would miss the sequence homology, that would be the exception, and not the rule.

Well that would depend on whether selection preserves or destroys the homology. Care to support your assertion here? DNA_Jock

Dr JDD:

HOWEVER, just because you can fold without a chaperone is not necessarily enough in the context of a cell, in particular a dynamic cell. Folding in vitro without molecular aids is quite inefficient and takes much much longer without chaperones.this is not a moot point and is important in the cell.

I read that the main reason genetic engineering has been so limited has been due to the foreign proteins not folding properly, if they folded at all. Insulin being one of the few victories. Dr Giuseppe Sermonti talks about it in "Why Is A Fly Not A Horse?". How can that be checked? (He was an editor for a peer-reviewed journal and a working geneticist for many years so he had access to that information.) Joe

gpuccio:

Who is Joe Gallien?

The person who cannot find the reference for his claim that proteins do not grow like stalagmites and stalactites because that would tend to bury the active site or make docking difficult to impossible. I didn't make it up, I just can't find it. Joe

DNA_jock, This discussion takes me to the fundamental place that most origins discussions end up - confusing experimental science and scientific fantasy. We can experimentally show that a lot of proteins do not "need" chaperones or other proteins to fold, however although it is hard to find a reference as you say the numbers I have read say 20-30% do absolutely require molecular aides for folding. Given that virtually all membrane proteins will require help and they maybe make up ~10% of proteins in mammals we could assume at best case 10% of cytosolic proteins require chaperones, etc. that is not insignificant, however the point firstly to address is "need" chaperones. What constitutes needing? Like I have said and you acknowledge aggregation is a problem and it is a fair point that purity does impact on this due to as you correctly say more hydrophobic interactions and novel interactions. We see this in production of our proteins that purity helps with less precipitation usually but you do need certain salts nd other buffers in the right concentrations. HOWEVER, just because you can fold without a chaperone is not necessarily enough in the context of a cell, in particular a dynamic cell. Folding in vitro without molecular aids is quite inefficient and takes much much longer without chaperones.this is not a moot point and is important in the cell. Now you could argue similar to as you have that pre-chaperone era that organisms were less fussy about the time to fold a protein so could "get by" without. But this is my first point. The only thing you can scientifically say is that not all proteins require chaperones to fold but all cellular life possess chaperones and have as far back as we have information for. When you state that there "was a time when chaperones were not needed" that is a fantasy argument as it is assuming that there must have been because of the assumption abiogenesis and UCD from abiogenesis. There is nothing to support this (abiogenesis) scientifically but rather it is a just so story and is no different to someone saying archaea, prokaryotes and eukaryotes were intelligently designed with chaperones and evolved from these points respectively. You say it is a common fallacy of ID to say that just because things are this way now means they couldn't have been diffently before but it is an equal fallacy to say they must have been different before otherwise they do not fit in with your worldview. I certainly would not argue with the sentiment that things we see now are probably much different to a long time ago, but if you actually take that argument for what it is and extend your own argument, you suddenly support YECs who will say that perhaps radioactive isotopes had different decay rates in the past hence the apparent very old ages. After all, just because something appears a certain way/rate now does not mean it always was! So it is fine for you to have your opinion on what we cannot observe and cannot test (that a cellular organism could exist without chaperones) but it is not based upon experimental science and is assumption and deduction to fit with your world view - no different to how one might conclude there needed to be a designer as all life have proteins needed to correctly produce other proteins necessary for life. Dr JDD

DNA_Jock at # 40:

And my statement above is true. That is precisely the argument that you made;

No.

I understand you may wish to dial it back, given that you have just been touting the functionality of a 5 amino acid peptide.

That is simply false, but think as you like.

Why did you add the word “specific”? As I explained previously, an alpha helix can have a function. Whether it`s “specific” or not is irrelevant semantics.

I added "specific" because I meant a secondary structure that is necessary for ots function as signal peptide. That would be "specific", I believe. And it would be a possible condition for positive natural selection. Yoiu may consider all that "irrelevant semantics". I don't.

And you know this how?

You show how you know that they are. It's your theory, not mine.

I`ll agree with you that “A functional peptide, however short, is functional.”

How kind you are!

But when you write “Secondary structure in itself is not function, and is not selectable.” , you are merely repeating the same tired, unsupported assertion. This is why I asked you for facts to support your various claims about what evolution cannot achieve.

Again, I would appreciate examples of generic isolated alpha helices which are naturally selected because they confer a reproductive advantage in a biological system. Again, it's your theory, not mine. You have to show the supporting facts.

This is rather misleading. Yes, by looking at DNA sequences, we can detect the recent recombination of relatively large fragments.

Why these strange limitations? The sequences in ATP syntase have remained almost the same for about 4 billion years. The Helix-loop-helix domain in human myc shows clearly detectable homology with the same domain in the mxl-3 protein in C. Elegans: 72 AAs, 31 identities (43%), 44 positives (61%), expect = 4e-06. The DBD in human myb protein (about 46 AAs) can be detected in C. Elegans with 46% identity and an expect of 4e-06. The WW domain, maybe the shortest protein domain in classifications, of about 40 AAs or less, can be clearly identified in dystrophin in humans and drosophila, with an expect of about 1e-08. And so on. Of course, very short sequences (5-20 AAs) will usually evade a simple homology analysis for statistical reasons, but as you certainly know simple motifs can be identified and studied by associating other methodologies. You see, functional sequences are generally conserved, both long and short ones, and homologies can easily be detected, even after billions of years. As a lot of conserved sequences or anyway of recurrent motifs, some of them very short, are well known, you can certainly show the relevant role of those sequences and motifs in building up long and complex functional proteins by recombination and natural selection. You must only show how those long amd complex functional proteins are simply the sum of existing, selectable sequences and motifs.

But, as I went to considerable lengths to explain to you, the absence of detectable homology DOES NOT preclude common ancestry.

You seem a little confused here. First of all, I have nothing against common ancestry. I have a lot, instead, against common ancestry and derivation by simple RV + NS. There is a big difference. Moreover, even if two proteins could have common ancestry and lack detectable homology (which is perfectly possible), still you have to find other reasons to affirm the common ancestry, if you lack detectable sequence homology: for example, strong structural homology could be considered a sign in favor of common ancestry even in the absence of obvious homology. But, if you have no facts in favor of common ancestry, it remains just a product of your imaginatiuon, with no scientific importance. And, even if we detect some sign of common ancestry, we still have to understand the mechanisms of transition from one form to the other. IOWs, you have to show that your theory (for example, RV + NS) can reasonably explain the transition. Common ancestry is a concept common to both your theory and mine. But I would never affirm common ancestry of two proteins in the absence of any empirical evidence. I try to keep my expectations and scientific facts separated.

I think you may have been seduced by the awesome power of DNA sequence alignment (and its ability generate molecular phylogenies is truly awesome).

I don't think that I have been "seduced". Like you, I recognize that power, and try to use it in my reasonings. If I have been "seduced" by anything, that is certainly ID theory.

The bottom line is that we can observe, today, processes of mutation, indels, and recombination that do cobble together different bits of proteins. If you wish to make a claim that these processes are inadequate to explain protein evolution, you need to support that claim with something other than bald assertions.

No. My point is simple. If recombination of functional modules were really a fundamental component in protein evolution, as many on your side have bben affirming, then we shopuld be able, in the general case, to recognize the functional modules which have been recombined, and therefore be able to analyze the role of recombination according to facts. While it can be true that in some cases we would miss the sequence homology, that would be the exception, and not the rule. As you have recognized, the power of homology (and possibly of other techniques of analysis) is very high. We see strong homologies in distant, very distant proteins, when the function is really conserved. Therefore, affirming that there can be exceptions is not the same as saying (as you do) that we cannot find the evidence. If the theory were true, the evidence would be there in tons. With a few exceptions, which, as everybody says, confirm the rule.

I understand that you are taking the “Joe Gallien” position that functional proteins cannot grow longer. To each his own.

Who is Joe Gallien? gpuccio

Dr JDD, You have my sympathy regarding your dodgy internet connection. You ask

given all cellular organisms we know of have molecular chaperones what evidence do we have that a cellular organism could produce proteins from genes/RNA for cellular life without needing such aides for folding correctly? And also, given we can fold proteins in a test tube quite easily but these are usually homogeneous, how did such an organism fold their proteins without detrimental peptide aggregation, assuming more than handful of proteins are necessary for their existence?

to answer your question,

It is a fair point that many proteins can and do fold quite easily, given the right buffer conditions. Not all absolutely require molecular chaperones and other folding proteins as we can produce a lot of useful proteins in the lab quite easily

I cannot find a source to support the wikipedia claim that "most" proteins do not require chaperones. Frankly, I`m not sure I believe that myself*. But my case doesn`t require "most": given billions of years of evolution WITH chaperones around, there hasn`t been any selection for chaperone-free folding. My case rests on the fact that a significant number of (extant) proteins do not require chaperones. (It seems to be a common ID fallacy that "if X is essential today then X must always have been essential"; see, for example, Andre's confusion over PCD.) You do make a good point, however, that aggregation is more likely to be a problem at higher protein concentrations e.g. the cellular environment. The homogeneity of your purified protein is not relevant - it`s the effective concentration of exposed hydrophobic surfaces that matters. But, by the same token, both correctly folded proteins and polysaccharides (if you are willing to allow their existence) act as volume excluders. They may also have mild detergent / weak anti-aggregation ability. *It is true that the vast majority of proteins do not require specific chaperones. DNA_Jock

DNA_Jock: I just wrote a rather lengthy response that due to a dodgy Internet and tablet was just deleted, and I cannot be bothered to go through it all again as most of these points we will just go around in circles with. Maybe next week when I'm home on my desktop! So briefly, I believe as you know, the answer to your question I think is 0 proteins but that insisting the point completely and yes the point is could a complex multi-protein machine arisen through naturalistic means and no I mean the higher eukaryotic large (>150+ proteins) spliceosomal protein complex. A question for you then: given all cellular organisms we know of have molecular chaperones what evidence do we have that a cellular organism could produce proteins from genes/RNA for cellular life without needing such aides for folding correctly? And also, given we can fold proteins in a test tube quite easily but these are usually homogeneous, how did such an organism fold their proteins without detrimental peptide aggregation, assuming more than handful of proteins are necessary for their existence? Dr JDD

DNA Joke- Those links do not help you. They don't even address what I am saying. Who cares how many proteins it takes to excise an intron? Your position cannot account for editing and splicing. Joe

Joe, Can. He. Understand. Basic. Biological. Science? See my 43 for links to the data. Re splicing, would you like to take a stab at my question

what is the minimum number of proteins needed to excise an intron?

or would you rather wait until Dr JDD comes to bail you out? DNA_Jock

Dr JDD, Re-reading this thread, I notice that you yourself wrote @38

That is to say, I think the evidence that short peptidic sequences with simple folds can combine over time to produce hugely complex proteins is very weak. I am not talking about repetitive sequences for example where proteins are involved in structural or architectural aspects of cells, I am talking about complex cellular machinery found all the way back to some of the most basic forms of life itself. [emphasis added]

which I took as a reference to collagen; but it could equally apply to titin and, given that you have published on titin, it seems safe to say that titin is an example of what you were not talking about. Regarding chaperones, my suspicion is that they originally arose as an adaptation to heat-shock; but once you have them, then the requirement that proteins be able to fold in their absence becomes moot. DNA_Jock

No DNA Joke, the data doesn't suggest otherwise. You have failed to provide any data for growing proteins. Also your position cannot explain splicing and editing- absolutely no data. Joe

Fascinating stuff, the spliceosome. Although someone reading your statement

the incredible complexity of the 150+ multi – protein spliceosome machinery

might make the mistake of thinking that 150 proteins are required for a spliceosome, rather than a 150 nucleotide snRNA... But do tell, what is the minimum number of proteins needed to excise an intron? A group I intron, for instance? I am happy to stipulate that life, as we know it, is complicated. The question is, could it have developed this complexity via natural processes? And what Joe wrote originally was:

additional amino acids will either alter or bury the active site. That is just the way it is.

The data suggest otherwise. DNA_Jock

7 - the incredible complexity of the 150+ multi - protein spliceosome machinery used to splice those 360-odd exons correctly. Titin is a fascinating protein regardless of your origins POV to be honest. But again screams design to me. Dr JDD

DNA Joke:

I agree that titin is complicated, but most of its size comes from duplication of the Ig-like domain, making it a terrible example for the lame argument “you cannot turn a small protein into a bigger protein”.

1- your position can't account for titin 2- It cannot account for the sequences it was allegedly duplicated from 3- It cannot account for exons and introns 4- It cannot account for alternative splicing 5- It can't even account for DNA 6- It definitely has no explanation for chaperones Joe

LoL! I posted a typo tintin at first and auto-corrected it to titan. But anyway I am looking for evidence for a polypeptide to grow, starting small with some function and remaining functional as it grew to titin. Anyone? Joe

Dr JDD, I agree that titin is complicated, but most of its size comes from duplication of the Ig-like domain, making it a terrible example for the lame argument "you cannot turn a small protein into a bigger protein". Re protein folding, my comments re re-folding @48 were a response to your statement

However many proteins are extremely difficult to produce and impossible to refold in vitro, in particular membrane proteins and it is a fair point that some of the most important proteins in the cell will not simply refold on their own in the right buffer. [emphasis added]

which I hope you can see is somewhat off-topic. Hence my emphasis on folding during de novo synthesis. I mean, what are we to conclude from the extreme difficulty in refolding a membrane protein in vitro? Not a lot. P.S. I've been giving Joe the benefit of the doubt for a long, long time. ;) DNA_Jock

DNA_jock, You have to give people (Joe here) the benefit of the doubt - I've published on Titin and the number of times it was autocorrected to Titan while preparing the manuscript I am amazed it didn't get published as Titan. Of course the standard response would be that it is duplication. But it is incredibly complex and the 17kb exon is of particular interest. While there are a lot of domain repeats there are unique large functional sequences, and within the repetitions there is clear necessity for functionality. The novex-3 isoform is interesting as well, but as we can see here there are a couple of main repeat domains but also several others organised in a precise functional structure: http://www.embl-hamburg.de/~wilmanns/Titin-Figure1.png Secondly I say "re-folded" because how else do you fold a protein without an organism? For when you use an organism such as e coli or CHO or SF9 or whatever you are hijacking their cellular machinery rather than using a native buffer - which is the POINT here: early proteins in abiogenesis/organism evolution would not have had chaperones or other proteinacious machinery to help fold them and that is what is argued here. Thus the best example to use surely is that some proteins can be denatured in the lab and then resold in buffer alone, showing that SOME proteins do not require such help to refold from other proteins... Dr JDD

Dr JDD, Re protein folding. Agreed. I would note that protein re-folding is far more difficult that protein folding during synthesis. Asking if a protein can re-fold is asking the wrong question. Strange to relate, but most proteins fold rather well as they are synthesized. Especially if they are expressed in a host from the same kingdom. DNA_Jock

Thank you Dr JDD for the clarification. Joe`s references to titan puzzled me. Nobody looking at the structure of titin would ever think that it arose via the duplication of the same simple sub-domains over and over and over again. No sirree. [/sarcasm] Best own goals evah. DNA_Jock

It is a fair point that many proteins can and do fold quite easily, given the right buffer conditions. Not all absolutely require molecular chaperones and other folding proteins as we can produce a lot of useful proteins in the lab quite easily (although a lot of the time we get bacteria to do the work for us). However many proteins are extremely difficult to produce and impossible to refold in vitro, in particular membrane proteins and it is a fair point that some of the most important proteins in the cell will not simply refold on their own in the right buffer. Dr JDD

What's the problem Joe? Do you not see how a 244 protein domain molecule with 363 exons one being >17kb in length alone can just come through selection of small peptides coming together over time? Maybe 244 different proteins decided to join together randomly alongside extra peptides to form the largest functional protein known in humans with a length of 1um. Seems plausible given enough time. After all it was necessary to come around to enable proper muscle and cardiac function. Dr JDD

DNA Joke- none of that even addresses what I said. Obviously you are deluded. Please provide the evidence that one of the small polypeptides gpuccio discussed can grow into something like titan. Or admit that you are a goal-post moving chump. Joe

I, too, am extremely fond of these kind of observations. It goes to the heart of the matter: IDists are impervious to evidence. See https://uncommondesc.wpengine.com/evolution/exon-shuffling-and-the-origins-of-protein-folds/#comment-551488 in particular: https://uncommondesc.wpengine.com/evolution/exon-shuffling-and-the-origins-of-protein-folds/#comment-551647 https://uncommondesc.wpengine.com/evolution/exon-shuffling-and-the-origins-of-protein-folds/#comment-551663 The simple fact is that (more often than not) heterologous gene expression and fusion proteins work as expected, including fusion proteins created with libraries of peptide fragments (e.g. yeast two-hybrid systems). Random recombinations between large proteins, OTOH, have a much more spotty prognosis, as expected, but some do have novel functionality. DNA_Jock

Joe: Meaning it doesn’t do any good to “grow” a protein if you don’t also have the proper accompanying chaperone(s)

I'm extremely fond of these kind of observations. It goes to heart of the matter: the cell is a whole. Under materialism one cannot insert an unrelated part into it - similarly one cannot just throw in an unrelated memory card into a computer. Regulation - in the broadest sense of the word - has to be in place. Box

DNA Joke:

I understand that you are taking the “Joe Gallien” position that functional proteins cannot grow longer.

It isn't my position. I take the position of those biologists and biochemists who I have read. They say that proteins are not like stalagmites and stalactites, meaning they are not just growths of amino acids. You don't get to titan by adding on to one of those short polypeptides all the while maintaining some function. Also:

It has recently become clear that protein folding in the cellular environment is not a spontaneous, energy-independent process akin to that observed when chemically denatured purified polypeptides are refolded in vitro. Rather, in vivo protein folding strongly relies on accessory proteins known as molecular chaperones and foldases.--Molecular Chaperones and Foldases (bold added)

Meaning it doesn't do any good to "grow" a protein if you don't also have the proper accompanying chaperone(s) Joe

Gpuccio writes:

DNA_Jock:

You have shifted your argument. On the FSCO/I vs needles thread, you argued that the sort of short peptides that might be accessible via random walk (I used the example of a stable alpha helix) could NOT confer a selectable advantage

Not true. The problem is not that whether a peptide is short or long. A signal peptide is functional because it is part of a recognition network.

Ah, yes, the context argument I predicted @27. And my statement above is true. That is precisely the argument that you made; I understand you may wish to dial it back, given that you have just been touting the functionality of a 5 amino acid peptide.

I have no idea if the miPEP171b peptide has a specific secondary structure or not. My point is that an alpha helix, in itself, has no specific function.

Why did you add the word “specific”? As I explained previously, an alpha helix can have a function. Whether it`s "specific" or not is irrelevant semantics.

And that longer proteins are not built by adding some generic isolated functional alpha helix to another one and to another one.

And you know this how?

Again, homology can detect recombination. Secondary structure in itself is not function, and is not selectable. A functional peptide, however short, is functional. Maybe selectable. Whatever its secondary, or tertiary structure. But if it is not an intermediate step to a longer functional sequence, it does not explain the longer functional sequence.

I`ll agree with you that “A functional peptide, however short, is functional.” But when you write “Secondary structure in itself is not function, and is not selectable.” , you are merely repeating the same tired, unsupported assertion. This is why I asked you for facts to support your various claims about what evolution cannot achieve. However, your response did offer a clue as to why you think the way you do (other than confirmation bias, of course…) : You wrote

Again, homology can detect recombination.

This is rather misleading. Yes, by looking at DNA sequences, we can detect the recent recombination of relatively large fragments. But, as I went to considerable lengths to explain to you, the absence of detectable homology DOES NOT preclude common ancestry. I think you may have been seduced by the awesome power of DNA sequence alignment (and its ability generate molecular phylogenies is truly awesome). The bottom line is that we can observe, today, processes of mutation, indels, and recombination that do cobble together different bits of proteins. If you wish to make a claim that these processes are inadequate to explain protein evolution, you need to support that claim with something other than bald assertions.

Is this so difficult to understand?

I understand that you are taking the "Joe Gallien" position that functional proteins cannot grow longer. To each his own. DNA_Jock

DNA_Jock: "You have shifted your argument. On the FSCO/I vs needles thread, you argued that the sort of short peptides that might be accessible via random walk (I used the example of a stable alpha helix) could NOT confer a selectable advantage" Not true. The problem is not that whether a peptide is short or long. A signal peptide is functional because it is part of a recognition network. I have no idea if the miPEP171b peptide has a specific secondary structure or not. My point is that an alpha helix, in itself, has no specific function. And that longer proteins are not built by adding some generic isolated functional alpha helix to another one and to another one. Again, homology can detect recombination. Secondary structure in itself is not function, and is not selectable. A functional peptide, however short, is functional. Maybe selectable. Whatever its secondary, or tertiary structure. But if it is not an intermediate step to a longer functional sequence, it does not explain the longer functional sequence. Is this so difficult to understand? gpuccio

DNA_jock, The reason people who oppose Darwinian evolution call such things fairy tales is these hypotheses are oft touted as fact - but they can only be considered factual as if they were not we would struggle to be able to accept or explain UCD otherwise. That is to say, I think the evidence that short peptidic sequences with simple folds can combine over time to produce hugely complex proteins is very weak. I am not talking about repetitive sequences for example where proteins are involved in structural or architectural aspects of cells, I am talking about complex cellular machinery found all the way back to some of the most basic forms of life itself. FYI I would not be personally surprised if short proteins could merge (I.e. the genes) and give a functional protein but functional here is again quite key in terms of complexity and also necessity. the other aspect of this is it is quite clear that many of these non coding regulatory RNAs that are being discovered are actually quite necessary in the control of the genes they help to regulate nd other processes necessary to life of that organism. Therefore this in a very simple sense raises 2 aspects of increasing the level of complexity that evolution must account for: 1) even less mutations are allowed than previously (as in this non coding space which is functional mutations are more likely to be deleterious to the organism) 2) even more than just a gene must arise through evolution, and many coordinated so with their regulatory counterparts as several studies are showing that many of these non-proteinacious products of the genome are in fact misregulated or mutated or aberantly expressed in cancer and other disease states. These to many people with an open mind to the ID vs materialist debate cause further doubt on the ability of naturalistic processes to solely account for this level of complexity in the genome. Dr JDD

Interesting, gpuccio. You have shifted your argument. On the FSCO/I vs needles thread, you argued that the sort of short peptides that might be accessible via random walk (I used the example of a stable alpha helix) could NOT confer a selectable advantage, yet here you are touting the functionality of a 5 amino acid peptide. Now you appear to be hanging your hat on the idea that functional proteins cannot grow larger -- the "Joe Gallien" position, as it were. Is this correct? DNA_Jock

There are many data suggesting that, in general, the proportion of non coding DNA is related to the complexity of organisms. Mattick has defended that concept in many papers.

Mattick has said this is many papers -- if he's ever made a genuine effort and defending such a claim I've not read it. wd400

Gpuccio,

Indeed I quoted Mattick. You seem not to like him. And so?

You didn't quote Mattick; you mentioned his name. Why do you think I don't like him? I only disagree with the idea illustrated with his (in?)famous plot. The relation between "complexity" and the amount of noncoding DNA is spurious, in my opinion. It's fair to say that eukaryotes (especially multicellular ones) are structurally more sophisticated than prokaryotes. But among eukaryotes there's very little if any correlation between phylogeny or complexity (however defined) and the amount (or proportion) of noncoding DNA. Even the contrast between prokaryotes and eukaryotes is not necessarily connected with their "complexity"; a more probably reason is the vast size of bacterial effective populations, making them susceptible to extremely small selection pressures. I'll explain that in detail if you want. Anyway, there are eukaryotes with hardly any noncoding (let alone junk) DNA, and they are not "simpler" in any way from their close cousins. Whatever the human complexity, the amount of noncoding DNA in our genome is not particularly outstanding, even among mammals (for example most marsupials have got significantly larger genomes but more or less the same amount of coding DNA; ditto for tarsiers, aardvarks, armadillos and many other mammal groups), not to mention many amphbians, lungfishes, and even shrimps. Parrots and corvids are thought to be very intelligent, but they have much less noncoding DNA than ostriches. Piotr

Aurelio, There isn't any theory of evolution and there isn't any evidence that prokaryotes can evolve into something other than prokaryotes. That means universal common descent can't even get started. As for ATP synthase- that "progress" has nothing to do with unguided evolution. Joe

Piotr: I apologize for the duplicate post. There was a problem with the upload. I am not trying to make my arguments "heavier" by sheer brute force! :) gpuccio

Piotr: Indeed I quoted Mattick. You seem not to like him. And so? My simple point is that there may be real effects and exceptions, and that exceptions should be understood, before building theories upon them. Regarding complexity, while I can agree that there is no simple way of measuring it in species, I would definitely say that a general gradiemt of complexity can be traced, in form, functions, biochemical networks, epigenetic regulations. With more complex forms emerging later than simpler forms. Would you question that eukaryotes are mopre complex than prokaryotes? Or that metazoa are more complex than unicellular forms? Just to know. And, even if maybe you are not available to think that humans, with their extremely complex nervous system and their cognitive abilities, are more complex than other metazoa, well, I tend to think so. gpuccio

Piotr: I quoted Mattick. You seem not to like him. And so? My simple point is that there may be real effects and exceptions, and that exceptions should be understood, before building theories upon them. Regarding complexity, while I can agree that there is no simple way of measuring it in species, I would definitely say that a general gradiemt of complexity can be traced, in form, functions, biochemical networks, epigenetic regulations. With more complex forms emerging later than simpler forms. Would you question that eukaryotes are mopre complex than prokaryotes? Or that metazoa are more complex than unicellular forms? Just to know. And, even if maybe you are not available to think that humans, with their extremely complex nervous system and their cognitive abilities, are more complex than other metazoa, well, I tend to think so. gpuccio

DNA_Jock: I cannot understand your reasoning. I have no problem in function for short peptides. Absolutely none. Short peptides work as signals. The same is true of siRNAs. Signals are signals. Their impèortance and function is due to their role in a network of recognition and meaning. What I definitely don't believe is that long and complex proteins, which effect important biochemical functions, like enzymatic reactions and so on, can be explained as the result of recombination of short functional motifs. That's the meaning of what I wrote, and that you kindly quoted: "Are you saying that you can explain the emergence of long and complex proteins or domains or superfamilies (whatever you prefer) as the result of reasonable recombinations of an existing pool of short motifs, each of which was expanded because in itself it conferred a reproductive advantage? Are you imagining some pre-LUCA whose main activity was to synthesize short alpha helices or beta sheets, selected in name of I don’t know what perspective, or short DNA binding motifs which bind DNA without having any other effect…" You should remember that, for RV and NS to work, two different things are necessary: a) Some functional sequences, short or long, must be selected, expanded and fixed. b) Those sequences must be intermediate states to the complex functional sequence of the final protein. Now, there may be a lot of short sequences which are functional, as signals or in other ways, and which may be more or less selected. In no way that helps your theory, unless you can show that the long complex sequences are "built" from those intermediate sequences, which can easily be verified by homology studies. So, unless you can show that functional peptides like miPEP171b are steps to, say, ATP synthase (or whatever you like), I cannot see any argument on your side. And I still wonder what is your problem, beyond misunderstanding my thoughts and words. gpuccio

Gpuccio,

There are many data suggesting that, in general, the proportion of non coding DNA is related to the complexity of organisms. Mattick has defended that concept in many papers.

Care to cite that data? But, please, not Mattick's "Dog's Ass Plot" or, as Ryan T. Gregory puts it,

[any] graphical representation of data in any field that, through a lack of clear axis labels, selective inclusion/exclusion of data, visual presentation style, and/or other questionable characteristics, generates a misleading interpretation of the data in the viewer, especially by implying an illusory pattern that is not supported by the available data.

If lungfishes, salamanders, onions, Easter lilies, etc. are "anomalies/exceptions", how do you know that humans aren't? And how is complexity measured? What's more complex? An eagle or an ostrich? An opossum or a human? A mouse or a bat? And how do you know? Piotr

Dr JDD, I have been quite aware of the functionality of short peptides for over 30 years, siRNAs for over ten. What surprises me is that gpuccio should be such a fan. Previously, he mocked the argument I was making about minimally selective peptides thus:

Are you saying that you can explain the emergence of long and complex proteins or domains or superfamilies (whatever you prefer) as the result of reasonable recombinations of an existing pool of short motifs, each of which was expanded because in itself it conferred a reproductive advantage? Are you imagining some pre-LUCA whose main activity was to synthesize short alpha helices or beta sheets, selected in name of I don’t know what perspective, or short DNA binding motifs which bind DNA without having any other effect...

To which I replied:

Yup, pretty much, but without the unnecessary value judgments. I am imagining some pre-LUCA’s who synthesized short alpha helices, beta sheets, helix-turn-helix motifs, etc., etc. and concatenations thereof, selected in name of some minimal selective advantage, such as DNA binding motifs which inhibit transcription, until they were out-competed by their fractionally less hopeless cousins. But, unfortunately, all the selection and extinction that has occurred since that time has badly fogged our view of this era. I doubt that we will ever know the historical truth about how early proteins did emerge, but – thanks to in vitro protein evolution studies – we do know a fair amount about what is feasible.

which drew the following response:

So I can apply the random walk model to any step which does not include selection. And I will accept NS only if it is supported by facts, not as a magic fairy accepted by default because of a pre commitment based on personal (or collective) faith.

and

Again, refer to my discussion about what science is. Science is not about what is possible, but about what is supported by facts.

Oookaaay. So I anticipate gpuccio arguing that, although short peptides are selectable in a modern context (as both of you insist), they are not selectable in a pre-LUCA context. All I ask for is some facts to support this position, not just "a pre commitment based on personal (or collective) faith". DNA_Jock

Why is it a surprise that short sequences are functional? Do you know what siRNA is? If RNA sequences si short can be so powerful why not peptides? Do you know anything about MHC class 1 peptide presentation? Dr JDD

DNA_Jock: I am afraid I don't understand your point, if you have one. Maybe my old age... gpuccio

gp, I'm just surprised to see you admit it openly. When you respond, citing "context", be careful to hold yourself to the same standards of evidentiary support that you demand of "evolutionists". DNA_Jock

tjguy #3, Exactly. And they are saying that we have the problem of the gaps ) EugeneS

DNA_Jock: Yes, that's what the paper says. Why are you surprised? I believe that short peptides have already been considered functional in many cases. This is just one example: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3764427/pdf/fpls-04-00352.pdf "Small signaling peptides arise from genes that typically encode an N-terminal signal peptide region, one or more conserved peptide domains and variable regions that flank one or both sides of the discrete peptide domains. There are two structural classes of signaling peptides: small (5–20 amino acids) posttranslationally modified peptides, which are the focus of this review;" Emphasis mine. So, why are you surprised? gpuccio

JoeCoder: I will start with your point about the c-value enigma. I absolutely agree. There are many data suggesting that, in general, the proportion of non coding DNA is related to the complexity of organisms. Mattick has defended that concept in many papers. Obviously, there are many extreme exceptions and anomalies. But I believe that they should be studied individually, rather than considering them as a reason to derive a general conclusion. So, I agree with your points about that, which are very well expressed. gpuccio

A 20 amino acid peptide and a five amino acid peptide? And they're functional? Really?... I`ll get me coat. DNA_Jock

DNA_Jock: "How long are these “short regulatory peptides”?" In the quoted paper, in "Extended Data Figure 1: Characterization of the M. truncatula miPEP171b", two "short putative ORFs" are represented, one of 20 AAs, one of 5. I suppose that's a good example. gpuccio

gp, How long are these "short regulatory peptides"? Thanks DNA_Jock

JoeCoder: I have looked at your arguments, and I must say that I agree with many of the things you say. However, I will try to take time to give my perspective too, while wd400 prepares his answers. :) gpuccio

wd400: "Such sequences will continue to be found, people that think genomes are almost junkless will keep harking on them, all the while ignoring the good arguments for very junky genomes." Until, in the end, the genome will be found to be almost completely functional, and the "good arguments for very junky genomes" will remain as a very good example of bad arguments defended for a long time by a lot of intelligent people because of cognitive bias. gpuccio

Hi Joe, I did miss your commen. it'll take a little while to respond to your points, but i will try to in the next few days. wd400

@wd400

ignoring the good arguments for very junky genomes.

Yesterday I replied to your arguments on junk DNA in a previous thread, but that thread was almost dead so you probably didn't see it. I would appreciate your thoughts and feedback because I want to know whether I'm right or wrong :) JoeCoder

And, as correctly stated by Dr JDD, the point is simply that other sequences (like those in the primary transcripts of miRNAs) have revealed completely unexpected function

In ~0.005% of the genome. Such sequences will continue to be found, people that think genomes are almost junkless will keep harking on them, all the while ignoring the good arguments for very junky genomes. wd400

Mapou: "Yeah, science is the real enemy of Darwinists, not religion." Absolutely. Science (indeed, reality itself) is definitely on our side! gpuccio

wd400: And, as correctly stated by Dr JDD, the point is simply that other sequences (like those in the primary transcripts of miRNAs) have revealed completely unexpected function. And the whole field of unknown short regulatory peptides is still there for us to investigate. gpuccio

wd400: Thank you for meeting my expectations (see post #2) :) OK, your comments are welcome anyway. At least you give facts, which cannot always be said of others... gpuccio

The .005% is from all the primary transcripts of miRNAs -- the same sequences used in the paper. In the human genome alpha-sattelite sequences make a couple of percent of the genome, some of those, in the centromeres, are required. Other satellite classes add up to very little. wd400

Actually wd400 are they not about miRNA precursors of which much less were known as it included additional sequence space originally not included as "functional"? So what % of the genome does satDNA make up then? Dr JDD

gpuccio @2, Yeah, science is the real enemy of Darwinists, not religion. Mapou

Andre:

if you are sceptical about RM & NS you are no doubt a bible bashing fundamentalist that have no IQ.

Throwing a rabid dog in the arena is a favorite tactic of materialists and Darwinists. It will come back to bite them in the ass. Sooner than they think. Mapou

The trend is in one direction only

Well.. yeah. Could it be otherwise? But y'all might want to keep some perspective. Two of these links relate to miRNA in plants. Most people wouldn't count miRNAs as junk DNA to start with. Even if you did, all the miRNAs in the human genome adds up to about 0.005% of the genome. wd400

I'm sure this will just go down as "what they expected" as per every other discovery that dents their idealistic interpretation of the data... Dr JDD

This is getting more and more embarrassing for the believers in junk DNA! The trend is in one direction only and it is relentless. The places they can still hide in are getting fewer and fewer in number. They are still safe for now to be sure, but they gotta be getting worried as they watch purpose and function encroaching on their space. tjguy

One small step at a time, our understanding increases. Luckily. Our darwinist friends will certainly be busy to count their remaining treasured "non functional DNA", like a miser who counts his remaining coins. The era of the epigenetics of cell regulation is only at its starting point. Understanding can only increase, and new multiple levels of designed complexity will emerge. But, as Andre says, RM & NS can do anything after all. And Wagner will readily argue that all epigenetic regulations derive from multiple platonic networks of functional states. What's the problem? gpuccio

Darwinian evolution predicts that everything has function RM & NS can do anything, even replace all designers, seriously, and if you are sceptical about RM & NS you are no doubt a bible bashing fundamentalist that have no IQ. Evolution optimizer for function and that is a fact sure as oxygen. Andre