Friday, July 03, 2015

The fuzzy thinking of John Parrington: The Central Dogma

My copy of The Deeper Genome: Why there's more to the human genome than meets the eye has arrived and I've finished reading it. It's a huge disappointment. Parrington makes no attempt to describe what's in your genome in more than general hand-waving terms. His main theme is that the genome is really complicated and so are we. Gosh, golly, gee whiz! Re-write the textbooks!

You will look in vain for any hard numbers such as the total number of genes or the amount of the genome devoted to centromeres, regulatory sequences etc. etc. [see What's in your genome?]. Instead, you will find a wishy-washy defense of ENCODE results and tributes to the views of John Mattick.

John Parrington is an Associate Professor of Cellular & Molecular Pharmacology at the University of Oxford (Oxford, UK). He works on the physiology of calcium signalling in mammals. This should make him well-qualified to write a book about biochemistry, molecular biology, and genomes. Unfortunately, his writing leaves a great deal to be desired. He seems to be part of a younger generation of scientists who were poorly trained as graduate students (he got his Ph.D. in 1992). He exhibits the same kind of fuzzy thinking as many of the ENCODE leaders.

Let me give you just one example.

Sandwalk readers will be familiar with the correct meaning of the Central Dogma of Molecular Biology. It says ...
The central dogma of molecular biology deals with the detailed residue-by-residue transfer of sequential information. It states that such information cannot be transferred from protein to either protein or nucleic acid. (F.H.C. Crick, 1970)
This is very clear. It says nothing about the definition of a gene and nothing about whether RNAs can be functional. In fact, Crick was no idiot (gasp!) he knew about tRNA genes and ribosomal RNA genes.

Parrington is one of those scientists who were never taught the real meaning of the Central Dogma. That's sad but it's understandable. However, like many other scientists, he writes about his misconceptions without ever checking the original papers or even thinking seriously about what he says. He promotes the idea that genes are stretches of DNA that encode proteins (no genes for functional RNAs) and that the Central Dogma of Molecular Biology is the basis of this belief.

Thus, the discovery of non-protein information (like RNA) is a paradigm shift that requires a new definition of a gene. There's a sense in which he is correct. Anyone who believes what he believes needs a paradigm shift. However, that shift in thinking should have occurred decades ago and it has nothing to do with the human genome project.

Here's how John Parrington describes the Central Dogma on pages 38-39.
The discovery of the genetic code signalled the primacy of the new discipline of molecular biology. Central to this was Crick's claim that life is a one-way flow of information from DNA to RNA to protein—the 'central dogma of molecular biology.' ...
This is not what Crick meant but, apparently, there are a lot of scientists who think this way. This lead to a great shock for them when they discovered functional RNAs (They were first discovered in the late 1960s and Nobel Prizes were awarded in 1989 for other functional RNAs. Some scientists are a bit behind in their reading.)

John Parrington realized in 2012 that there was something wrong. He writes on pages 91-91 ...
The [ENCODE] study also found that 80 percent of the human genome was generating RNA transcripts. In line with these transcripts having functional importance, many were found in specific cellular compartments, indicating that they have fixed addresses where they operate. Surely there could hardly be a greater divergence from Crick's central dogma than this demonstration that RNAs were produced in far greater numbers across the genome thatn could be expected if they were simply intermediates between DNA and protein. Indeed, some ENCODE researchers argued that the basic unit of inheritance should now be considered as the transcript. So Stamatoyannopoulos claimed that 'the project has splayed an important role in changing our concept of a gene.'
The ENCODE project will, indeed, have done some good if it causes people like Parrington and Stamatoyannopoulos to finally get up to date on their concept of a gene. But, since the modern concept of a gene as "a DNA sequence that is transcribed to produce a functional product" includes functional RNAs as well as proteins, and since that concept is at least forty years old, one wonders why a practicing scientist would want to advertise the fact that they are so out-of-date.

And why would they want to mislead the public?

You may think I'm being unfair. John Parrington isn't the only scientist to misunderstand the Central Dogma. True enough, but most scientists don't write books about it and don't bother to read the relevant papers. Recall that the discovery of reverse transcriptase raised questions about the Central Dogma back in the late 1960s. This prompted Crick to write the Nature paper that corrected any false impressions about refuting the Central Dogma (Crick, 1970). He made it clear that the flow of information from RNA to DNA had nothing to do with the Central Dogma of Molecular Biology. That was allowed in the original 1958 version (Crick, 1958).

But here's how John Parrington describes it on page 118.
The recognition that RNA can code for DNA was one of the the first challenges to Crick's central dogma that the information can only flow in one direction, via RNA to proteins. We saw in Chapter 3 how, since proteins are required to replicate and transcribe DNA, it could equally be valid to see information flowing back to DNA from proteins. Nevertheless, this is information flow in an indirect sense. In contrast, turning an RNA sequence into DNA is a very literal challenge to the central dogma, and this reversal of information requires a specific enzyme—reverse transcriptase.
This is fuzzy thinking and it's just one of many examples in the book. This is why it is such a pain to read and it's why I have no confidence in the conclusions of the author. It's also why I'm going to have such a hard time discussing Parrington's views on junk DNA because those views are colored by deep misunderstandings of fundamental principles of biochemistry and molecular biology. It's going to take as much effort as discussing Jonathan Wells' book [The Myth of Junk DNA by Jonathan Wells]. Maybe I should just have you read those posts from 2011. They pretty much cover all the problems with Parrington's book except for the ENCODE stuff.


Crick, F.H.C. (1958) On protein synthesis. Symp. Soc. Exp. Biol. XII:138-163

Crick, F. (1970) Central Dogma of Molecular Biology. Nature 227, 561-563. [PDF file]

107 comments :

  1. This is just another in a long line of posts that boils down to: 'Only I, Larry Moran understand biology. Everyone else is a Moron."

    Its like the sound of one hand clapping.

    Did you hear it? Just now. Its not easy to catch, though. Oh, there it is again!

    Utterly profane...er I mean profound....definetely profound!!

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    1. It's probably a waste of time answering such a stupid and ignorant comment, but for your information many people in this group agree with Larry about what the central dogma is, and many (if not, alas, all) biochemists in general. If you want to be educated Dan Graur recently displayed Crick's original diagram illustrating what he meant on his blog (Judge Starling), which leaves no doubt that he meant what Larry said and not what ignorant authors like John Parrington seem to think.

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    2. Which part of Crick's own explanation of the "central dogma" is beyond your mental powers, Steve?

      http://www.nature.com/nature/focus/crick/pdf/crick227.pdf

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    3. Steve doesn't understand anything about what is being discussed. He only thinks that, in some way, conventional science has been challenged - therefore, he is on board.

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    4. Steve doesn't even appear to understand the idea behind the "sound of one hand clapping", let alone the science discussed in the post. A continued conversation seems futile.

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    5. What is stupid, ignorant and a waste of time is for so-called scientists like Larry Moran holding on to old ideas.

      If science truly is self-policing, self-regulating, etc etc as the regulars here are so fond of pointing out to IDiots, then there should be little in the way of criticism of opposing points of view.

      Rather, the stagnant state of biology begs for more explanatory frameworks then what is currently on offer by the likes of Larry Moran.

      Revolutions in science take place when there is active challenge to the status quo.

      Is the genome truly full of bits and pieces of functionless genetic flotsam?
      It appears not. Is there slam-dunk evidence? No, not yet. Is there reason to believe we will find evidence?? Yes. Should we go on looking? By all means. Literally, by ALL means. Is it rational to do so? Without doubt.

      Shit, Moran's position is the more anti-science one simply because he is in effect saying he is smarter than everyone else and he KNOWS those genetic bits are functionless because he can't SEE any function, he can't imagine any function. Therefore, we must all bow to Moran's greater power and deeper insights into the genome. Surely, we are all wasting our time digging into the question of why all those bits and pieces of DNA are still hanging around since they are so OBVIOUSLY functionless?

      Rather, the robustness of Life puts smart (and rational) money on Parrington's more scientifically open POV.

      Moran's take will be increasingly seen (if it isnt already) as a drag on scientific discovery. Its pointless and counterproductive.

      Thats why I love when Moran calls his detractors IDiots. It highlights his own insecurity about the future of biology.

      But thats the way of Dogma.





      Athe Cornish-Bowden says: It's probably a waste of time answering such a stupid and ignorant comment, but for your information many people in this group agree with Larry about what the central dogma is, and many (if not, alas, all) biochemists in general. If you want to be educated Dan Graur recently displayed Crick's original diagram illustrating what he meant on his blog (Judge Starling), which leaves no doubt that he meant what Larry said and not what ignorant authors like John Parrington seem to think.

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    6. "This is just another in a long line of posts that boils down to: 'Only I, Larry Moran understand biology. Everyone else is a Moron.""

      I didn't get that impression at all. I was taught the central dogma in my molecular biology classes the same way Larry teaches it, so it can't just be because Larry is some arrogant asshole who thinks he's the only guy who gets it. Apparenly some obscure teacher at a Danish college was taught and is teaching the central dogma the way Larry does. Isn't that weird?

      Maybe, just maybe, this Parrington dude is just wrong and for the reasons Larry state? We could bother to read Crick's original publications to find out. You up for it, Steve? Lets read those two references and then cite the key passages to see who is correct? You up for that challenge?

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    7. I challenge any competent scientist to a public debate on junk DNA. I wiil present solid scientific evidence that most of our genome is junk. In fact, I will defend the proposition that 90% of our genome has no biological function.

      I am very confident that my view of the human genome is more realistic than the views of those scientists who think they have identified function in most of our genome.

      Steve, how much money are you willing to wager on such a debate? Would you put up $1000 to back John Parrington?

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    8. What IDiots like "Steve" don;t seem to understand is that their dismissive rants make it look like THEY think that they are right about everything and everyone else is wrong - IDiots are among the most spectacular examples of the Dunning-Kruger effect that one can hope to encounter. Or, more likely, hope not to encounter.

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    9. Steve, you've overlooked an important fact regarding "junk" DNA. We actually know what a lot of it is -- broken genes, "dead" viruses, and bits of our own RNA written back into DNA complete with poly-A tails. We know these (usually) things don't do anything useful for us.

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    10. Challenging accepted scientific ideas is a legitimate scientific activity. Challenges not accompanied by good evidence will be legitimately dismissed, and those presented by people who demonstrate that they do not understand what they are challenging will be met with legitimate derision.

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    11. No matter how many times Larry or anyone else presents any particular bit of evidence that most of the genome is junk, Steve and his friends will read that evidence as saying what he presents as Larry's argument above: "he KNOWS those genetic bits are functionless because he can't SEE any function, he can't imagine any function". In other words, it isn't that he doesn't agree with Larry's argument; he doesn't even see Larry's argument. He has carefully taught himself not to notice anything that might make him uncomfortable.

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    12. The size of the" bit of evidence" is a problem and it's relevance just in case you didn't know....'...
      ..........

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    13. Ah, KevNick is obsessed with size. Is he compensating for something?

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    14. I'm being nice ....nothing next to wishful thinking is all you got... lies. vs we have a hypothesis that has no evidence to support it, but it is scientific... then it must be true.......

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    15. "nothing next to wishful thinking is all you got... lies. vs we have a hypothesis that has no evidence to support it, but it is scientific... then it must be true......."

      What the hell does this crap even mean?

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    16. "Steve, how much money are you willing to wager on such a debate? Would you put up $1000 to back John Parrington?"

      I putting up the some amount of money that you and THE BLINDS will never provide even one piece of evidence that convinced you the most about abiogenesis. Who do you think will win Larry?

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    17. @KevNik

      I know you have a lot of trouble with reading and comprehension so let me tell you one more time in block letters ...

      I DO NOT KNOW HOW LIFE ORIGINATED.

      If you know the answer to how simple forms of life began about 3.5 billion y, then feel free to share your knowledge right here, right now.

      If you fail to come up with a good explanation, then I wiil delete all further posts from you that attempt to move the goalposts from evolution to abiogenesis.

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    18. KevNick/Quest sounds drunker than Sarah Palin on YouTube

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    19. Larry, KevNick can truthfully say he never claimed abiogenesis. What he's claimed is something incredibly more difficult and less likely, abiodeisis. That is, here's nothing and up pops God. So the Universe can't muster up a virus or amoeba, but an all-powerful, omniscient superbeing? No problem for KevNick, right? C'mon, Kev, step by step, with equations, the scientific description of the origin of God.

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    20. Abiodeisis... JSYKIST (Just so you know I'm stealing that.)

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    21. This "prove abiogenesis" shit is getting boring, because the religionists have had basically all of history to prove abiodeisis.

      We aren't asking for much here, I can be instantly swayed to believe in a supernatural origin if a creationist can show me the instantaneous and divine creation of anything made of atoms that can be seen well with the naked eye.

      I don't need to see macro-creation, micro-creation will do. That will convince me that macro creation is also possible. The instantaneous and divine creation of a beetle for example, in a sealed-off glass container, under controlled conditions. It doesn't have to be a new species never seen before, so no "speciation", no macro-creation. It can be a species of beetle that already exists. So only micro-creation.

      Anyone ever seen micro-creation? At least I have seen microevolution happen. But not even micro-creation has been ever demonstrated.

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    22. My path into evolutionary biology was eclectic: a lot of development, a good dose of comparative phys & anatomy, a solid foundation in genetics. and a great deal of cell bio. I teach cell bio & genetics now.

      And sorry, but all my teachers way back in the 70s and 80s were on board with Larry's understanding of the dogma; beginning in the 90s, most of them came around to his views on junk DNA, too. (well, not his views, let's not give him that much credit -- they were the standard views of most of the evo biologists I knew).

      That said, though, I was on a panel just last weekend where I got into a public argument with a smart young biologist who simply could not accept the idea that most of the genome was junk. It was entertaining but depressing.

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    23. Is there a link for that talk please Dr. Myers?

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    24. Yup..... John Harshamn, I'm compensating for your lack of evidence.
      Here is one: why does the blow fish (related subject to your dark interests) have almost no "junk DNA" at all? I don't wanna hear the probably Darwinian BS.
      Explain it with scientific evidence not with the one for the faithful......

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    25. This comment has been removed by the author.

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    26. QuesDick, Larry asked you to explain the origin of life or be banned. I notice you have not.

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    27. why does the blow fish (related subject to your dark interests) have almost no "junk DNA" at all?

      'Cause Baby Jeebus loves fugu better than people, so he took more care in designing blowfish?

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    28. Judmarc's answer says most of it, but a major focus of the argument about junk DNA relates to the huge and arbitrary variations in the amount of DNA in different organisms. Why do some organisms not noticeably more complex than humans, like onions, lungfish and Gonyaulax polyedra, have great deal more DNA, whereas others, like your fugu, have much less? Because that's the way God wanted it is one answer, but it doesn't say much for His skill as a designer. If you don't want to admit that Gonyaulax has many more functional genes than humans do then you have to conclude that it has a lot of junk, and if it has a lot of junk why not us?

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    29. A nitpicky note - I'd be careful making arguments based on dinoflagellates, the rules are somewhat different there - we don't actually know what exactly that genome contains.

      The argument is correct in general, of course.

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    30. @Larry,

      I think you misunderstood my intentions.

      1. I never claimed that I knew how life originated
      2. I challenged you and the rest of the flock to provide ONLY 1 PIECE OF EVIDENCE THAT CONVINCED YOU (and the flock) that life originated on its own. You and the flock didn’t do it.
      3. Instead of providing 1 piece of evidence that convinced you that life originated on its own, you challenged me to explain the origins of life. Also, where did the conditions set by you come from and WHY???

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    31. KevNick, you IDiot. If there's no positive evidence, the only sensible answer is "we don't know how life originated"
      But a natural explanation is leaps & bounds more plausible than the ridiculous fairy tales in the book of genesis

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    32. Life is irreducibly complex so there is no way it could've originated by chance. Anyone who believes in abiogenesis can be compared to someone who believes that an electric drill assembled itself and then built a house.
      There is no derogatory name in a dictionary to describe such stupidity and obvious blindness.

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    33. KevNick seems to think that admitting we don't know something is the same as admitting that we don't know anything.

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    34. @Sceptical mind: Irreducible complexity is not a thing. Claiming life is IC doesn't make it true, particularly when IC essentially amounts to "look at this, it's irreducibly complex". Are ID researchers working shifts to apply Behe's (non existent) method to identify irreducibly complex organisms?

      Look at yourself in the mirror when you accuse others of stupidity: God's purported creation of life out of clay or whatever bullshit you believe in is abiogenesis too

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    35. Anyone who believes in abiogenesis can be compared to someone who believes that an electric drill assembled itself and then built a house.

      And then how much more idiotic does one have to be to think the workman who built the drill either was magically poofed into existence, or has been alive since prior to the beginning of the universe and will live on eternally?

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    36. Dazz
      Irreducible complexity is not a thing.

      No? What then?

      Claiming life is IC doesn't make it true, particularly when IC essentially amounts to "look at this, it's irreducibly complex". Are ID researchers working shifts to apply Behe's (non existent) method to identify irreducibly complex organisms?

      It looks like Dazz has no idea what irreducible complexity is.

      Oh yeah? Does claiming that life is not irreducibly complex without any evidence how life originated make it true?

      Look at yourself in the mirror when you accuse others of stupidity: God's purported creation of life out of clay or whatever bullshit you believe in is abiogenesis too

      Give me one reason why I should try to explain you the latter if you have no idea what you are talking about?

      Look up what the scientific explanation is for the origin of life elements starting with big bang? Look in the mirror and ask yourself: what is my stupid head made of? Clay/dust/earth or whatever you call the elements that the universe and human body was made of after the big bang.

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    37. Septic Mind,

      "Life is irreducibly complex so there is no way it could've originated by chance."

      Mere assertion. I would bet impossible to prove that life is irreducibly complex, and then again, worse if you're using the definition that has the conclusion hidden, as in "irreducibly complex is a thing that missing a single component breaks into useless crap, and that could not have evolved," in which case is an assertion that is clearly false. Many individuals die, and life continues. So much for missing parts break it and render it useless.

      As per natural abiogenesis (I think this is what you meant, but who knows, you're stupid). That life arose naturally doesn't mean that it arose "by chance."

      Anyone who believes in abiogenesis can be compared to someone who believes that an electric drill assembled itself and then built a house."

      Only if you're stupid enough to think that drills are comparable to life, and that everything is natural, except life. Care to prove that life is supernatural?

      You seem to be under the impression that gods are there. That gods are the "natural" conclusion when confronted with hard problems, like the question of how life originated. But that would be no better than those primitive tribes thinking that the volcano is an angry god. So, where's the proof that gods exists? Ah, it's your your superstitious beliefs? I thought so.

      "There is no derogatory name in a dictionary to describe such stupidity and obvious blindness."

      Like the blindness necessary to ignore that you're no better than a volcano worshipper?

      I think you have no idea what Sceptical means. You're easily convinced that gods-did-it is a meaningful answer. There's no derogatory name in the dictionary that would describe your self-unawareness, stupidity, ignorance, and blindness. We're stuck with calling you an IDiot.

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    38. Irreducible complexity is not a thing.

      No? What then?


      An ever changing, unscientific, bold assertion of truth, a ridiculous negative argument from personal incredulity. A useless, question begging brain fart.

      But two can play that game. I'm going to just affirm that god is irreducibly complex because without Jeebus or the holy rapist pidgeon it could never retain his brainwashing function, hence, some other super god, one that is actually intelligent must have created him. Am I doing good science now?

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    39. Skeptical Mind says,

      Life is irreducibly complex so there is no way it could've originated by chance

      I see lots of biological systems that are irreducibly complex by any reasonable definition [see The meaning of "irreducible complexity"]. That does NOT mean they didn't evolve. We have lots of good explanations for the evolution of irreducibly complex systems in modern organisms.

      This argument from ignorance fails at the first step. Creationists assume that just because a system is irreducibly complex then it could not have possibly arisen by natural means and gods must have created it. All we have to do is show hypothetically that one irreducibly complex system could easily arise by entirely natural means in order to refute that argument.

      In many cases we actually have good evidence that our explanation is correct [see Blown Out of the Water].
      We have done that many times but the creationists ignore the examples we've given. That's why I call them IDiots.

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    40. Daz

      You've just proven that you are a moron but also just a lousy troll that is pissed off because he has no arguments.

      Ciao idiota!

      Delete
    41. Larry

      To make the long story short, provide a reasonable explanation on how the first self-replicating molecule evolved by avoiding the obvious problem of irreducible complexity. What I mean by irreducibly complexity problem here is that all elements of the molecule would have to be in the same place and at the same time in order for self-replication to begin its function.

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    42. Sceptical Mind, this article seems a pretty direct response to your question:

      Scott et al. 2014. RNA catalysis, thermodynamics, and the origin of life. Life 4: 131-141. doi:10.3390/life4020131 (http://www.mdpi.com/2075-1729/4/2/131)

      (A bit of background: we already know that components of RNA can self-assemble, and that some RNAs can catalyze their own replication.)

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    43. Larry

      Here is a specific example of the interdependence of DNA, RNA and protein. DNA, RNA and proteins cannot do their jobs without the help of at least one of the other two.

      On the top of that a living cell needs all three molecules at the same time. Not only these three are needed for life, but they need a cell membrane, energy ect.

      Cell membrane can't be made without proteins and proteins can't be made without cell membrane and the story goes on and on.

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    44. bwilson, good article - I've read it previously, as the lead author's a friend.

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    45. and the story goes on and on

      Indeed it does, since you don't understand enough to know that Larry already answered your objection in his last comment.

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    46. This comment has been removed by the author.

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    47. Sceptic Mind,

      U Mad? Why am I a moron for doing the same exact thing that you did?
      I make a claim that god is irreducibly complex, hence, it must be true, right?
      And since IC is a central argument for the Grand Theory Of Intelligent Design, we can conclude that god was designed. What's the problem? Do I have to conclude that IC is not about design, but just a pathetic negative argument against evolution then? I really hope not, it would be a huge blow to the well established GTOID. This could potentially put an end to my research on ID. I have this experiment going on where I put all these primordial molecules on a dish of spaghetti carbonara and left it for weeks out of the fridge, and if I can get some living forms to arise, we'll finally have good evidence that the Flying Spaghetti Monster is the Grand Designer of life. Wish me luck!

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  2. Well, Piotr, Crick says he should be careful in declaring the Central Dogma as dogma.

    So it seems it would be beyond anyone's mental powers to grasp the importance of a self-confessed dogma-less dogma.

    I mean really, can that dog actually hunt??

    What modern science is finding is that life resists any human attempt at dogmatically asserting what life can do information wise.

    So that goes to the heart of the matter. Is life restricted to a certain set of information transfer protocols.

    Why not start with the assumption that life uses a slew of methods to stay ahead of entropy. so let figure out what they are?

    So now back to those seemingly functionless bits of genetic flotsam??!! Not so fast. We have good reason to believe life is a lot more crafty than current science lets on.

    How do we know?? Our multi-billion dollar efforts tell us so.

    Now, THAT is science in action.



    Crick: 'Although the details of the classification proposed here are plausible, our knowledge of molecular biology, even in one cell - let alone for all the organisms in nature - is still far too incomplete to allow us to assert dogmatically that it is correct...."

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    1. Steve,

      Crick's hypothesis (called, somewhat tongue-in-cheek, the "central dogma" of molecular biology) doesn't have to be true. It isn't an axiom but an empirically testable (and falsifiable) scientific hypothesis. It says that biological processes use only nucleic acids, and not proteins, to store sequential information. In other words,

      (1) no natural process translates a protein back into RNA or DNA sequence;

      (2) no natural process makes a new copy of a protein by scanning and replicating its amino acid sequence.

      If you discover a process that does either of these things, you will shake the foundations of molecular biology and probably win a Nobel Prize.

      There are people with degrees in biochemistry or biology who wrongly believe that the central dogma is about something else. Larry Moran only points out that such people should know better. When they proclaim another "challenge to the central dogma" without as much as bothering to check what Crick really meant by it, it makes them look foolish and -- well -- incompetent.

      A final note: the central dogma has zilch to do with junk DNA or "our multi-billion dollar efforts". (Why "our", by the way? Do you work for the ENCODE project?)

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    2. Piotr, though I do enjoy reading what you write, and indeed it would seem that even material as dense as Steve's skull ought not to be impervious to the childishly simple drawings shown in the paper you cite or at Dan Graur's Judge Starling blog (as Athel Cornish-Bowden noted above), I think SRM has unfortunately nailed it:

      Steve doesn't understand anything about what is being discussed. He only thinks that, in some way, conventional science has been challenged - therefore, he is on board.

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    3. Steve the non-scientist:
      "What modern science is finding is that life resists any human attempt at dogmatically asserting what life can do information wise."

      What modern non-scientists are finding is that they will glom on to anything that seems to remotely prop up their anti-evolution, anti-science beliefs so that at some level, they can justify their silly ancient beliefs regarding deities and miracles.

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    4. Steve,

      The central dogma was much more of a proposition than an actual dogmatic pronunciation. According to Horace Freeland Judson (who interviewed all of those guys), Crick thought that "dogma" meant something that there was not enough evidence for. So it was a naming mistake, but the name prevailed.

      What Larry's is complaining about, is not that the dogma should stand forever, but that those who say that they have found it broken are talking about something else. not about the central dogma. It's a complain about lack of understanding, not a zeal to defend a "real" dogma from being broken.

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  3. Turning from shooting IDiot fish in a barrel to something that may actually be interesting, Larry, what are your thoughts about Arlin Stoltzfus' comment on Dan Graur's recent Central Dogma post?

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    1. I'm also curious what Larry's thoughts would be. As for me, I don't think the kind of post-translational modification mentioned by Arlin comes anywhere close to violating Crick's rule. There is no transfer of sequential information from the enzyme that catalyses the modification to the protein that gets modified; that is, the sequence resulting from the modification is not encoded in the amino acid sequence of the enzyme.

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    2. I don't see how protein modifications break any of the "rules" in the central dogma. I therefore don;t see why we should be curious as to what Larry would think, other than "this guy did not understand the central dogma." Too obvious.

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    3. Oh, I only wondered if perhaps I'd missed something. Arlin Stoltzfus isn't normally the kind of guy who blithely ignores the history of the discipline and gets fundamental concepts wrong. I don't see how his comment could undermine the validity of the central dogma, but then I'm not a specialist.

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    4. I agree it is a misunderstanding to say posttranslational modification is a violation of the "central dogma", because there is no passing of nucleic acid sequence information into amino acid sequence. A ribozyme of some sort might be able to somehow alter a protein by cutting it, or inserting another amino acid somewhere or similar, but you cannot look at the modifying molecule and say "that residue right there 'translates' into that amino acid", there are no "hard rules" like that that would apply to all cases of post-translational modification in the same way there is with complementary base-pairing, tRNA amino acylation and all that.

      Another one of the things I always understood the central dogma to be saying is that there is no mechanism by which the sequence of amino acids in a protein can be reverse-translated back into the same nucleic acid sequence it was originally translated from due to codon redundancy. The amino acid sequence simply doesn't contain that information.

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    5. a protein can be reverse-translated back into the same nucleic acid sequence it was originally translated from

      I think it's stronger than that. The central dogma says that a protein can't be reverse-translated, period. Not into the same DNA sequence, and not into a different but synonymous sequence.

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    6. Well, I don't believe that is true. I know that it isn't being reverse translated, and that no such machinery exists in the cells now that can do this. But is it impossible in principle? I'm not so sure.

      For example, imagine the process of translation running in reverse. A protein enters the ribosome, which catalyzes the splitting of the peptide bonds between the amino acids, which are picked up by tRNA's, which have an anti-codon site that could theoretically bind a small, complementary RNA-trimer, which could be ligated together sequentially by a kind of RNA polymerase. Impossible?

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    7. The central dogma isn't about what's impossible in principle. It's about what actually happens. A reverse-translator of any sort, including just reverse-translation to RNA, would violate the central dogma.

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    8. If the central dogma were merely a rewording of the fact that the genetic code is degenerate (and so exact reverse translation is impossible in principle), it would be true in a trivial way, and rather uninteresting. But it says more than that: the protein sequence could be but is never employed as information storage by extant life (as far as we know). That's why there are neither reverse-translating not protein-copying "molecular machines".

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    9. Sorry, for not read nor in the last sentence.

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    10. "The central dogma isn't about what's impossible in principle. It's about what actually happens. A reverse-translator of any sort, including just reverse-translation to RNA, would violate the central dogma."

      Yeah but, that's not what you said when you wrote: "The central dogma says that a protein can't be reverse-translated, period."

      You wrote it can't be, not just that it isn't being.

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    11. By "can't be" I meant "can't be without violating the central dogma", not physical impossibility. Sorry for any misunderstanding.

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    12. I think it is also physically impossible -- how could it possibly work? A nucleotide sequence can describe a unique protein sequence, but a protein sequence cannot describe a unique nucleotide sequence because of the ambiguity in the genetic code. Translation is a lossy process. Just like how you can make a fuzzy JPG from a crisp TIFF but not the inverse.

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    13. The central dogma was much more of a proposition than an actual dogmatic attempt. According to Horace Freeland Judson (who interviewed all of those guys), Crick thought that "dogma" meant something that there was not enough evidence for. So it was a naming mistake, but the name prevailed.

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    14. Jonathan,

      I think reverse translation that simply produced a DNA sequence synonymous with the one that was originally translated would be good enough. And it wouldn't be fuzzy, either.

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    15. The central dogma isn't about what's impossible in principle. It's about what actually happens. A reverse-translator of any sort, including just reverse-translation to RNA, would violate the central dogma.

      Which of course, as all of us (non-creationist, non-anti-science types) would know, if a new enzyme was discovered tomorrow that could reverse translate in any way, it would be fascinating functionally and mechanistically. But its least importance would be that it overturned a general idea conceived in the 1950s. No doubt Crick was right, but if he was wrong about that... who could care?

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    16. Although Jonathan is right that reverse translation to the exact DNA sequence is impossible, a weaker form of reverse translation, simply to get one possible sequence, is conceivable, even though we know that it doesn't happen. The other day, for a different purpose, I calculated how many different genes could encode histone H4. Assuming that I calculated it correctly it came to a surprisingly huge number: 2 times 10^55. Only 14 of these are actually used in humans.

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    17. I'm in the 'impossible' camp. A process that could unfold a folded protein to read its sequence is unlikely to provide an environment that could support a function folded enzyme to do the reading, to say nothing of the difficulty of reading accurately along such a 'lumpy' surface, or avoiding interacting with it. Anticodons work because of interaction, not despite it.

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    18. Unlikely: yes, we can all agree; highly unlikely, even. But that's not the same as impossible.

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    19. In particular, we humans have the means to read the amino acid sequence of a protein and synthesise an artificial gene that encodes an identical protein. It just doesn't happen naturally in living cells at the molecular level.

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    20. No, I stand by 'impossible'! Impossible for a cell to evolve the means to reverse translate, due to the physical restrictions imparted by the very structures of protein and nucleic acid. Cells can't employ centrifuges, fractionation columns and the like. They are restricted to groping their way around substrates, and those substrates would need to interact strongly to allow distinction between very similar side-chains, but weakly in order to allow a protein to be unwound and read like a tape. I don't think these conflicting requirements are available even in principle, at the single binding site which would be necessary to cater for multiple distinct targets during the reading process.

      It's strong claim, though I will cheerfully retract it as soon as someone comes up with a non-hand-wavy way of it being 'possible'! (I realise I sound like an abiogenesis-denier).

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    21. I think your best argument is the issue of coming up with a fits-all method for unfolding a folded protein. I agree, that's one of those "on the face of it I can't even imagine in principle how that might operate". As a first hurdle I think you have a strong case for a dealbreaker there :P

      I'm much less convinced by the issue of accurate recognition of residues in a peptide chain. After all, there are proteins that can accurately discriminate between binding sites on other proteins at the single residue level.

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    22. Mikkel,

      I'm much less convinced by the issue of accurate recognition of residues in a peptide chain. After all, there are proteins that can accurately discriminate between binding sites on other proteins at the single residue level.

      Sure, but ... I guess we are talking of something like a 'reverse ribosome' - a set of carriers with a triplet at one end and a discriminatory amino acid binding site at the other. The somehow-unfolded peptide passes through and carriers bind most strongly to their 'cognate amino acid', enabling close approach of the triplet and phosphate-bonding to the growing end.

      I dunno, I can't really put my finger on it, but something strikes me as fundamentally unworkable about that scenario. What would we make the 'tRNA equivalent' out of? Make it out of protein, and you have to stop it being unfolded itself, and ensure that it does not otherwise become entangled with the 'tape'. Peptides have a habit of interacting, and making a 'reader for all seasons' would be a tough nut to crack. Make it out of RNA, I don't think you have the same opportunity for precise specificity, though I could be wrong on that.

      And ... where did these readable proteins actually come from?

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    23. can't really put my finger on it, but something strikes me as fundamentally unworkable about that scenario.

      This seems a typical example of what Richard Dawkins calls an argument from personal incredulity.

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    24. Me: can't really put my finger on it, but something strikes me as fundamentally unworkable about that scenario.

      Athel: This seems a typical example of what Richard Dawkins calls an argument from personal incredulity.


      Ouch! I think I have given some rational detail of the basis of my incredulity, that sound-bite nothwithstanding. "I can't see how aliens can regularly visit this planet", or " I can't see what would lead one to to accept Sheldrake's 'formative causation'" are also examples of arguments from personal incredulity. We do it all the time. A valid follow-on tends to be "because ... ", which I did, and which is the thing to address, rather than the bare fact of 'incredulity'.

      To put my incredulity on a still firmer footing, note my final sentence - "and ... where did these readable proteins actually come from?". It's not just the biochemical difficulties (which are significant): people are proposing an evolutionary scenario in which the necessary preconditions are just parachuted in from nowhere. If an organism can already make the protein from DNA, it just needs to make some more. It does not need to deconstruct one of the proteins it just made in order to reconstitute its DNA sequence. If the protein is external, how does it distinguish the useful from the deadly, on the basis of one molecule? And if it can't make protein, what use is the capacity to convert an externally-sourced protein into what would be a transcript if it had such a thing? Nope, I can't quite put my finger on it, but ... ;)

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    25. But I think Athel has a point... there are many enzyme complexes that carry out manipulations of such astounding complexity that it would be tough to believe were the evidence not before our eyes.

      So long as actual physical or chemical principles are not broken, it is perilous to say that a proposed molecular process could not possibly evolve, even as we accept that in all liklihood such a process has in fact not evolved.

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    26. Mmmm. I have a point too! I think the Central Dogma underscores a very central point in evolution - something else one can read in Dawkins, besides that 'personal incredulity' thing - the primacy of replication for evolution. I don't think the direction is a mere frozen accident, but a mechanistic necessity for evolutionary reasons. My biochemical argument is admittedly weaker - though beware: simply because one can imagine a fancy setup where a mechanism can 'read' every residue in an unwound peptide without getting glued to it or unwound itself somewhere along the line does not mean it is possible.

      But the evolutionary issue is more central, as I sketched above. It does not just need to be mechanistically possible - within the reach of a super-duper Designer, say - it has to be evolutionarily possible. And that's not just a question of overcoming the biochemical mechanistic barriers. The information flow is from replicators - 'for whose benefit', in Dawkinsian terms, the whole shebang is orchestrated - to phenotype for a reason.

      Transcription is partial replication. It enables multiple copies of a protein to be produced, just as full replication enables multiple copies of the entire genome. These are powerful tools. But going the other way involves essentially 'using' proteins as a mutagen. Creating sequences you either already have (if you made 'em in the first place), can't use (if you have no translation machinery), or stand a very good chance of being fatally inconvenienced by. This (to me) is devoid of evolutionary logic. You can do this occasionally (see LGT) but do it wholesale and you are screwed. Meantime, for the mechanism to become fixed, and counter the mutation load, it's no use being useful once in a while. I am open to persuasion, but 'don't you be so sure' isn't really compelling.

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  4. "In fact, I will defend the proposition that 90% of our genome has no biological function. "

    Impossible

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    1. Impossible

      Enlightening.

      Of course, Nicholas of Cusa did say, "Ignorance will enlighten us in incomprehensible ways," so perhaps this is one such instance.

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    2. In defense of Unknown, I think s/he meant to say "Inconceivable!".

      Vizzini: He didn’t fall?! Inconceivable!
      Inigo Montoya: You keep using that word. I do not think it means what you think it means.

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    3. "Impossible"

      Impossible huh? Not just unlikely, or maybe unproven or something? Simply impossible! Why? Because of your intense religious halluscinations demand it to be so.

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    4. Guys, time to move on. Unknown just proved beyond any reasonable doubt that there's no junk DNA and the onion is god's special creation. All praise the onion gawd!

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  5. Steve: "If science truly is self-policing, self-regulating, etc etc as the regulars here are so fond of pointing out to IDiots, then there should be little in the way of criticism of opposing points of view."

    No, there should be much criticism of opposing points of view. If the opposing points of view make more sense, they will be listened to an followed up on. So far, ID has not made any sense. But keep trying. It is entertaining.

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  6. Less and less the so-called junk DNA.


    "Carrying around a spare tire is a good thing -- you never know when you'll get a flat. Turns out we're all carrying around "spare tires" in our genomes, too. Today, in ACS Central Science, researchers report that an extra set of guanines (or "G"s) in our DNA may function just like a "spare" to help prevent many cancers from developing.

    Various kinds of damage can happen to DNA, making it unstable, which is a hallmark of cancer. One common way that our genetic material can be harmed is from a phenomenon called oxidative stress. When our bodies process certain chemicals or even by simply breathing, one of the products is a form of oxygen that can acutely damage DNA bases, predominantly the Gs. In order to stay cancer-free, our bodies must repair this DNA. Interestingly, where it counts -- in a regulatory DNA structure called a G-quadruplex -- the damaged G is not repaired via the typical repair mechanisms. However, people somehow do not develop cancers at the high rate that these insults occur. Cynthia Burrows, Susan Wallace and colleagues sought to unravel this conundrum.

    The researchers scanned the sequences of known human oncogenes associated with cancer, and found that many contain the four G-stretches necessary for quadruplex formation and a fifth G-stretch one or more bases downstream. The team showed that these extra Gs could act like a "spare tire," getting swapped in as needed to allow damage removal by the typical repair machinery. When they exposed these quadruplex-forming sequences to oxidative stress in vitro, a series of different tests indicated that the extra Gs allowed the damages to fold out from the quadruplex structure, and become accessible to the repair enzymes. They further point out that G-quadruplexes are highly conserved in many genomes, indicating that this could be a factory-installed safety feature across many forms of life."

    http://www.sciencedaily.com/releases/2015/07/150706114123.htm

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    1. Septic Mind wishes is to believe that Junk DNA is disproven by stretches of functional G's. But of course he has the "Divide by 3 Billion" problem. Septic Mind did not tell us the number of non-coding base pairs that are known to be functional, and divide that by the size of the genome-- 3.2 billion base pairs.

      Because the resulting percentage would be tiny.

      The Discovery Institute had taught him well how to mislead the public. Doesn't work on us though.

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    2. The IDiots never actually try to add up all those tiny percentages representing known types of functional DNA. If they did, they would see for themselves that the sum converges on something of the order of 10% (if that). And other lines of reasoning support a similar figure:

      Rands et al. 2014. "8.2% of the Human Genome Is Constrained: Variation in Rates of Turnover across Functional Element Classes in the Human Lineage"

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    3. Why don't you explain why the amount of apparent junk in the DNA vary so spectacularly? You have fish that have almost none of it, like puffer fish and fish that have a lot, like lungfish.

      The same variation applies to plants, mammals etc.

      The funniest thing is that prokaryotes, like bacteria don't even have anywhere near this level of variation.

      Seems that natural selection acts in mysterious and magical ways.

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    4. Septic Mind,

      "Why don't you explain why the amount of apparent junk in the DNA vary so spectacularly? You have fish that have almost none of it, like puffer fish and fish that have a lot, like lungfish."

      Exactly you idiot. This variation is one of those things that suggest that a lot of that stuff is junk. Useless stuff. So it can vary without consequences.

      "The same variation applies to plants, mammals etc."

      No kidding! (you imbecile).

      "The funniest thing is that prokaryotes, like bacteria don't even have anywhere near this level of variation."

      Yup. Have you ever read anything about population genetics, and reproduction rates as it applies to this "mystery"? Of course not,. You're an illiterate idiot.

      "Seems that natural selection acts in mysterious and magical ways."

      Seems like you don't understand what "natural selection" means. If something is invisible to selection, then it won't matter if there's much or little (you idiot). If there's population bottlenecks, then lots of stuff will prevail despite natural selection. Natural selection is not the only one explanation for everything we see in life forms, despite what your miseducation might suggest.

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  7. I don’t understand Crick’s Dogma. Nothing in “information theory” forbids information from flowing from proteins to DNA. And nothing in biochemistry forbids it either. So what’s stopping this from happening?

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    1. Nothing stops it from happening. Just doesn't.

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    2. What stops it is that there's no biochemical machinery that does it.

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    3. ... which probably tells us something important about the history of information pathways in living organisms. Since this fundamental constraint does not seem to be physical or biochemical, it's likely to be of historical origin (a "frozen accident").

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  8. I was led to believe that just about every piece of biochemical machinery that operates on DNA leaves behind a characteristic trace of its activities, in the form of base modifications, substitutions, additions, and deletions.

    But since the purport of Crick’s Dogma is just Weismann’s Doctrine...

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    1. Led by whom? Anyway, that's not a violation of Crick's 'dogma'. That's the whole point.

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  9. Thanks for the helpful feedback. I’m still trying…

    So, in fact, the flow of information completes the loop, and upon completion of the loop, DNA-seq is modified quite specifically, but non-adaptively. I.e., the statistical preponderance of the heritable genetic information generated during “closure” is maladaptive.

    I think if Crick made that argument, the Central Dogma of Molecular Biology is that most mutations are maladaptive then I would have understood immediately!

    Seems to me, all the rest is exactly what led to my confusion.

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    1. I think if Crick made that argument, the Central Dogma of Molecular Biology is that most mutations are maladaptive then I would have understood immediately!

      It really seems you are straining to misunderstand - any particular reason for that?

      Most mutations are neutral, and will have no discernable effect on phenotype. In any case, doesn't really have anything to do with the Central Dogma, which is at root a fairly simple idea (don't confuse simple with obvious, when we are talking about thinking circa 1950s).

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  10. However variation is introduced into the genome it is only per chance that it is adaptive.

    Crick’s argument reduces to this?

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    1. Crick's argument has absolutely nothing to do with that.

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  11. “It really seems you are straining to misunderstand - any particular reason for that?”

    What did I misunderstand?

    “A fairly simple idea”--

    Crick: Hereditary information is transferred from DNA to protein and not from protein to DNA.

    Did I get that wrong?

    Lets step through this, line upon line and word upon word if you so choose. But where did I get this wrong?

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    1. What did I misunderstand?

      Well, I did not see any of the points you made above in your earlier posts. This blog is populated by creationists who depend upon misunderstanding to perpetuate the conversation.. So when I see someone talking about maladaptism in connection to the Central Dogma.. I wonder. Perhaps you are legimately curious.. if so, I apologize and encourage you to ask more questions.

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  12. It seems strange that one would tout the fact that the human genome, e.g., is mostly “junk” (a rather non-descript term), but fail to recognize how this “junk” is generated.

    Proteins are potent mutagens.

    The very fact that our genomes are mostly “junk” is due to the fact that proteins are powerful catalysts of evolutionary change. So, the “missing link” in Crick’s is supplied.

    I tried to save it, update it, in exactly the way a biochemistry professor told me, ca. 1975:

    Crick’s Dogma is just Weismann’s Doctrine.

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  13. I know that once the topic disappears off the end of the page anything that is said is forgotten.

    Crick’s Dogma is false and there isn’t a biochemist or molecular biologist today who cannot routinely demonstrate it’s false.

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  14. Now I'm just repeating myself.

    Thanks for the input.

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