Tuesday, February 04, 2014

IDiots discover that RNA has secondary structure

I suppose we should be happy whenever some IDiots manage to educate themselves but somehow I find it quite sad when it takes thirty or forty years. Here's an example of a somewhat late-blossoming IDiot who posts on Evolution News & Views (sic): RNA Shows Design, Too. She doesn't sign her name to the post—I think I know why.

Here's what she just discovered ...
RNA differs from DNA in one of the sugars that makes up its backbone and one of the bases that makes up its side branches (uracil instead of thymine); it is also usually found in single strands instead of DNA's double helix. New discoveries, though, are showing RNA does far more than passively transfer DNA's information to other places. It, too, is a masterpiece of intelligent design and function.

A paper in Nature describes how information is stored not only in RNA's base sequence, but in its folds. Because RNA has more degrees of freedom, it can take on a wide variety of forms not possible for DNA. "RNA has a dual role as an informational molecule and a direct effector of biological tasks. The latter function is enabled by RNA's ability to adopt complex secondary and tertiary folds and thus has motivated extensive computational and experimental efforts for determining RNA structures," the authors begin (emphasis added). In their conclusion, they say, "We identify hundreds of specific mRNA regions that are highly structured in vivo, and we show for three examples that these structures affect protein expression."
The paper by Rouskin et al. (2014) reports on the development of new software to detect secondary structure in RNA. This is news for IDiots who think that "new discoveries" show that RNA is capable of catalysis and other functions.

Think about that for a minute. This is 2014, it's 25 years since Sidney Altman and Tom Cech were awarded the 1989 Nobel Prize in Chemistry and more that 30 years since undergraduates were routinely taught about catalytic RNAs in introductory biochemistry courses. Those IDiots sure are slow learners.
In other words, the structure, not just the sequence, carries functional information.
Amazing. Sounds like they've never heard of the idea that ribosomal RNA catalyzes peptide bond formation and that it does so through secondary structure. They've never heard of self-splicing introns. All they have to do is read an introductory textbook of biochemistry or molecular biology.

Now if you connect this amazing new bit of information to the equally astonishing (not!) news that some lincRNAs have a function, you get this ....
More design found in what was formerly called junk; more information found parallel to existing information in RNA; more power found in the collective energy of intelligent agents. Why are you not surprised?
The real question is why are IDiots surprised by routine information that even high school students know?

And what does this have to do with intelligent agents? Has this person answered the quiz?


  1. and the intelligent design of tRNA structures also suggests god is a leprechaun

  2. They still haven't figured out the whole ribosomal RNA thing - Stephen Meyer refers to a "protein within the ribosome known as the peptidyl transferase" and the "protein-dominated ribosome" in Signature in the Cell. And as I recall, that anonymous EVN author claimed a few years ago that "the PTC has been considered the oldest part of the ribosomal protein". So yeah, still haven't figured that one out.

    1. "the PTC has been considered the oldest part of the ribosomal protein".

      The work I suspect is being mangled, Harish & Caetano-Anolles, used phyogenetic methods to uncover the relative ages of the various components of the system. Phylogenetic methods that, in other contexts, Creationists insist don't work. But it might undermine the RNA hypothesis, so ... rubbish methodology; love the conclusion!

    2. I found David's quotes from that IDiot Stephen Meyer difficult to believe, because who could be that arrogant and stupid? It always astonishes me when ID proponents can't tell proteins, DNA and RNA apart. The "Philosopher of Science" Steve Fuller (who showed up blathering in the movie "Expelled") has also made this DNA=protein mistake repeatedly. However basic, it's a common error among IDiots.

      Because I found David's quotes hard to believe-- and because it's dangerous for us to cite evidence that seems "too good (or bad) to be true" from our POV-- I had to look up the source.

      True, as turns out. Here are the originals in context.

      For those of you who don't know already, here's why this is bad. The most important functional parts of the ribosome are ribozymes, i.e. catalytic RNA molecules, which are very, very different from proteins. Meyer says that the proteins in the ribosome do the catalysis, when in fact it's the RNA ribozymes in the ribosome that do the catalysis. This difference is crucial to the RNA World hypothesis, that the origin of life went through a stage of self-replicating RNA molecules before there were protein molecules. Every grad. student and all bright undergrads in mol. biol. must know this. It's pretty basic.

      Meyer's blunders are critically important to the whole thesis of his book Signature in the Cell, because he's trying to shoot down RNA World, so switching "RNA" and "protein" is very bad for science, though good for ID. Why do all their errors always point in the same direction?

      Stephen Meyer, IDIOT, on the formation of peptide chains by the ribosome: "The protein chain can now begin to form [on the ribosome]. An additional amino acid– tRNA combination (known as an aminoacyl-tRNA molecule) binds to a second and adjacent active site on the ribosome, bringing its amino acid into close proximity to the first [on the growing peptide]. A protein within the ribosome known as a peptidyl transferase then catalyzes a polymerization (linking) reaction involving the two (tRNA-borne) amino acids. [Stephen Meyer, Signature in the Cell, p. ?-128, Kindle locations 2102-2112]

      In the next quote Meyer repeats his error by again asserting that the proteins in the ribosome do the catalysis. But he compounds his error in two ways:

      1. He wants to claim that only God could create life, his proof being that science can't explain the origin of life, so God did it, and his evidence science can't explain it is that RNA ribozymes are all inefficient at catalysis compared to proteins; and his evidence for that is that catalysis in the ribosome is carried out by proteins, not RNA ribozymes, says he. But it's the reverse, so his cannon goes off in his own face.

      2. He calls the ribosome "protein-dominated" when it is RNA-dominated, its core is RNA with proteins on the outside, and its catalytic functions are carried out by RNA, not proteins, so this reverses his moronic point. This was the most important result when the structure of the ribosome was solved, and led to the awarding of the 2009 Nobel Prize in medicine, so getting it wrong is very bad.

      Stephen Meyer: "Similar limitations affect the RNA catalysts that have been shown to be capable of peptidyl-transferase activity (i.e., catalyzing peptide bonds between amino acids). These ribozymes (made of free-standing ribosomal RNA) compare quite unfavorably with the capacities of the protein-dominated ribosomes that perform this function in extant cells. For example, researchers have found that free-standing ribosomal RNA can only catalyze peptide-bond formation in the presence of another catalyst. More important, apart from the proteins of the ribosome, freestanding ribosomal RNA does not force amino acids to link together into linear chains, which is essential to protein function. [Stephen Meyer, Signature in the Cell, p.309]

    3. David also says: "And as I recall, that anonymous EVN [ENV] author claimed a few years ago that "the PTC has been considered the oldest part of the ribosomal protein". So yeah, still haven't figured that one out."

      Not quote an exact quote. Here is the original:

      Anonymous ENV author [possibly Meyer], 2012: "Traditionally, the PTC [peptidyl transferase center] active site has been considered the oldest part of the ribosomal protein. The idea behind stems from function, as well as an assumption that the proteins were built up in a step-by-step fashion. If this was the case, the outer components are likely "newer." [A New Study Questions RNA World. Anonymous. Evolution News & Views. March 16, 2012. ]

    4. Bingo! Harish and Caetano--Anolles it was. I claim a small prize.

      Mention the RNA world to a Creationist and that paper comes back. "Proteins are older than RNA". So we're buying phylogenetic methods now are we? "Er ... no".

    5. The second extended Meyer quote you've dug up is just awful. In addition to the whole "protein-dominated ribosome", Meyer claims that 1) peptidyl transferase ribozymes are made of ribosomal RNA and 2) that these ribozymes are quite limited because they require "another catalyst". (1) is wrong - the Zhang and Cech papers he cites _evolved_ ribozymes from random sequence, they are not free-standing ribosomal RNA. With (2) it's hard to tell what Meyer was even thinking: my best guess is that the other catalyst he's referring to is magnesium, which is the only thing that could be considered "another catalyst" mentioned in the Zhang and Cech paper. If so, that's absurd - first, they don't even show that magnesium is playing a catalytic role, it may just be required for ribozyme folding (as it is for proper folding and function of the "protein dominated" ribosome); second, even if it is a cofactor involved directly in catalysis, that is incredibly common, not a weakness of the ribozyme. Many enzymes, protein and RNA, use metals, and magnesium specifically is used by all of a cell's RNA and DNA polymerases, the spliceosome etc; it's also one of the most common elements in both the crust and sea water. Listing this as a "limitation" of the ribozyme is just grasping at straws.

    6. With (2) it's hard to tell what Meyer was even thinking: my best guess is that the other catalyst he's referring to is magnesium, which is the only thing that could be considered "another catalyst" mentioned in the Zhang and Cech paper.

      I was wondering if he was referring to the ability of ribosome to function when stripped of one or more ribosomal proteins. Doesn't matter - still has nothing to do with ribosomal proteins being catalysts.

  3. My god! The creationists figured out that RNA has secondary structure! How can we possibly compete with their 35 year old science?

    ID is the cutting edge! If they ever figure out that water molecules have oxygen AND hydrogen, we're screwed!

    Darwinism is finished.

    1. yes but how do oxygen atoms know they should bind to hydrogen atoms to form water? Don't tell me those atoms figured that out without supreme guidance.

    2. "yes but how do oxygen atoms know they should bind to hydrogen atoms to form water? Don't tell me those atoms figured that out without supreme guidance."

      Poe's Law applies. Your ridiculous parody position is Aquinas' fifth way: 'some intelligent being exists by whom all natural things are directed to their end'.

      That, said with a straight face and held as true by Christian scholars of many different factions, states exactly what you just said: that the only possible way hydrogen and oxygen can form water is if God stuck them together with the specific purpose of becoming water.

      This, of course, is a 'non mechanistic' process, because if it was mechanistic, science would be able to detect it. So he does it using magic or possibly ghosts.

      If you're ever confronted by a theologian, ask them *how*. *How* does a non-contingent being flick the first domino to start the universe if it isn't a physical process? How is a soul connected to a body? How does a hydrogen atom know God's arranged an HHO threeway for it? Just ask them to sketch in some basics ... are a constant stream of orders beamed to the atom, or is its destiny encoded in the atom itself?

      This isn't the Ken Ham ignorant Christianity. This is the theology of people who've not just got the Bible, they've read it. And other books. This is their *good* answer.

      These are the people falling over themselves to say they're not the guy Bill Nye Seahawked last night. They believe in stuff that's even more stupid. Now the world's seen the emptiness of intelligent design, now Ken Ham has spent three hours and a lot of money proving beyond all doubt that ID is a Christian movement, it's time to move on to 'mainstream' Christianity.

    3. Jem, in fact I've seen creationists argue that it is impossible to make water by any means, that hydrogen cannot burn with oxygen and make water, and aggressively defend this even when presented with videos of hydrogen burning and making water.

      Here's a link where creationist "JRS" denies that hydrogen can burn and make water and then, for dozens of pages, continues to defend this assertion aggressively after being presented with video evidence to the contrary.

      If you can stomach it, it's many pages of comedy.

      "Let me see you take Hydrogen, and oxygen to make water?
      God can. But the smartest man ever to live can't.
      Your random selection fantasy actually has a designer.
      And you can't duplicate your "random" selection even though it is simply hydrogen and oxygen. No matter how hard you try.
      Hmmm. So much for the theory of evolutionary happenstance."

      [Creationist JRS says no scientist can create water by combining hydrogen and oxygen]

      Checkmate, Smarty-pants Evolutionists, with your fancy "hydrogen combustion"!

    4. "after being presented with video evidence"

      Nice touch.

      But you genuinely can not win this one. If you take two things and swirl them around a test tube and say 'look, they combine', they'll say 'yes, if an intelligent designer swirls them around'.

      I once just got fed up of the 'banana is designed' line, and just laid out the history of the banana. Pretty much every banana we eat was selectively bred in the early nineteenth century from an original plantain by the Cavendish family in the greenhouses at Chatsworth. They become longer, curvier and fleshier. I linked, I showed ever step of it. The bananas you buy in supermarkets are manmade things - clones, in fact - and every step of that is documented.

      And the response ... 'so you're saying bananas DID have an intelligent designer?'.

    5. That, said with a straight face and held as true by Christian scholars of many different factions, states exactly what you just said: that the only possible way hydrogen and oxygen can form water is if God stuck them together with the specific purpose of becoming water.

      Yes (I was mimicking rather than parodyzing).

      This issue also speaks to a larger one I think, concerning Intelligent Design. Sometimes ID is rather narrowly interpreted as having to do mainly with the U.S., with Christianity, and with science curricula. But it is a much bigger problem than that, as it provides a fundamental basis for the notion that everything (from biological structure to the formation of water molecules) can be deduced in a scientific way as evidence of the action of god (whatever that god might be). The problem with ID is not just the effect it might have in schools or the impact it has on the most extreme of religionists, but that a major percentage of the earth's citizens have ears that are very receptive to the idea.

    6. sentence above should/could have said: "narrowly interpreted as having to do mainly with the U.S., with Christianity, and with the teaching of evolution."

  4. IDiots will try place there God wherever they can, as they have no proof for a god or their pseudo-science. This is remarkably sad in that they are making a point that this is new information that has never been seen before.

  5. on a tangent here... it just occcured to me:

    if secondary structure carries functional information, that would mean not all funtional information is sequential.

    That said, would it be too far a stretch to suggest that protein modification of nucleic acid could constitute yet another contradiction of the Central Dogma?

    or... is that too far a stretch?

    1. Too far a stretch. The Dogma states that sequential information cannot flow from protein to nucleic acid, not that protein cannot affect DNA/RNA. Reverse translation.

      Protein modifies DNA in many ways, including binding to it to prevent or promote transcription - methylation is simply in that class, but reversibly modifying the bases rather than sitting on top of them. Protein even creates sequences without a template, such as telomerase. The latter is closest to a violation, but as it does not use a peptide template, it isn't.

    2. Secondary structure in proteins and nucleic acids is dependent upon primary structure (sequence).
      It would be tough to figure how that constitutes a contradiction of the Central Dogma in any case. Search this site for posts concerning the Central Dogma.

    3. OK – help me out here:
      I teach my students the following:

      The emergence of life for the first time on this planet constitutes the classic question of what came first; the chicken or the egg?!

      Did a self-replicating DNA system occur before transcription or translation evolved (the DNA World) or did a self-replicating RNA system first emerge (the RNA world) or did self-replicating protein system first emerge (the Protein World)…or did replication, transcription and translation (or some combination thereof) emerge together all at once?

      I also teach my students that the regulation of the level of certain metabolites can also be controlled by “riboswitches. For the benefit of noncognoscenti bystanders: A riboswitch is section of the 5'-untranslated region (5'-UTR) in a molecule of messenger RNA (mRNA) which has a specific binding site for the metabolite (or a chemical on the same metabolic pathway). It has been suggested that these regulatory mechanisms, which do not involve any protein, are relics from an "RNA world".

      I also teach that ribosomes are a special instance of ribozymes.

      OK – everbody still with me?

      I also elaborate in class that so far the “RNA World” hypothesis seems (according to my reading) the leading contender as far as alternate hypotheses are concerned.

      That all said an alternate and cogent alternative called the ‘protein interaction world’ hypothesis is another strong contender that could explain the earliest emergence of abiogenesis.



      I had already searched Laurence Moran’s earlier posts on the question which still left me unsatisfied and scratching my head. Maybe I did not find them all.

      In many ways - protein elaborations are similar in kind to riboswitches. I am awed by the size complexity of the proteome vs the transcriptome. Check out the following:


      Some estimates suggest that 5% (approximately 50,000!!!) of the proteome comprises enzymes that alone perform more than 200 types of post-translational modifications on a far larger repertoire of proteins including an ever growing list of enzymes. This crucial 5% includes kinases, phosphatases, transferases and ligases (as well as other kinds of post-translational modifications) which add or remove functional groups, proteins, lipids or sugars to or from amino acid side chains; not to mention proteases, which cleave peptide bonds to remove specific sequences or regulatory subunits. Many proteins can even modify themselves using autocatalytic domains, such as autokinase and autoprotolytic domains.

      This is beginning to sound (to my dilettante ear) very similar to riboswitches.

    4. OK - to follow my line of thought (such as it is)

      Yes, I understand:

      Francis Crick defined the Central Dogma of Genetics as

      “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 back from protein to either protein or nucleic acid.”

      ITMT exists no equivalent machinery to some putative “reverse translatase”…

      But hold on: the RNA World Hypothesis presumes some version of autocatalytic RNA self-replication that exists no more. As I understand it, the Protein-Interaction world presents not too dissimilar postulates.

      So if riboswitches can be imagined as relics from an "RNA world", why cannot protein autocatalysis be similarly imagined as some putative relic of informational transfer in an earlier protein domain (if not world).

      And if it turns out that one hypothesis turns true and not the other; at least the very notion of informational transfer from protein to protein is not inconceivable. In other words the notion that protein systems can engage in the transfer of information by invoking a different category of molecular memory is not to be ruled out.

      Simply said, perhaps Cricks’ original definition was too constrained.

    5. Crick's definition was based upon modern life, but also on sound molecular principles. Perhaps we're a bit bamboozled by the way the system actually works, but it seems a practical non-starter for any molecular system to read the 'lumpy' edge of a peptide chain (which also has the damnable habit of folding up in physiological conditions) and have a smooth passage that can still accurately identify the acids. Whereas 'reading' RNA by virtue of docking charged tRNAs on codon-anticodon interaction is little different from reading it to template-copy, a smooth passage along a relatively straight edge. .

      If you want my 3 cents, I'd go for RNA first. I've not heard a convincing scenario for specification in any 'protein-first' theory. But a 'hard problem' rarely mentioned is the difficulty of getting not just bases, but bases that have a complement to permit antiparallel complementarity, necessary for both replication and ribozyme folding. I favour hybridisation as a first step - a way of purifying short homochiral chains of complementary sequence out of a general mess. Ribozymes would be formed by partial replication of one strand - transcription, essentially. You don't need to unfold ribozymes to replicate them, you just chuck them when you're done; the double-stranded RNA genome can't fold.

      So from the beginning, there is a double-stranded complementary genotype from which phenotype is extracted. Peptide bonding may be an early advance in this system, potentially including catalytic peptide-RNA complexes. Charging tRNA and aligning helps drive bond formation, with anticodon docking providing one means of effecting such an alignment, and permitting the emergence of 'true' protein coding.

    6. the degeneracy of the genetic code insures you could never re-generate the original DNA sequence from reading a sequence of amino acids

    7. the degeneracy of the genetic code insures you could never re-generate the original DNA sequence from reading a sequence of amino acids

      True, but that is not a fundamental property, but a contingent one. In its present form degeneracy prevents precisely reversible conversion, but not conversion per se, which is prevented by more fundamental molecular properties.

    8. Do you happen to know of any accessible formal discussions about the mechanistic barriers to such a system or is this just a reasonable inference. Leaving aside the folded polypeptide problem (which I don’t think would be a barrier in all cases) I suppose the initial difficulty would concern the evolved ability to discriminate multiple sidechains with fidelity (that’s just one of the difficulties of course). Anyway, it seems such a system has never evolved so it is something close to a moot point, but I wonder if there are any good discussions regarding the mechanistic barriers I can look at.

    9. SRM - no, I'm afraid it's largely my own surmise! A number of issues suggest themselves - the constantly varying profile of the side chains is one. If one imagines a macromolecule 'scanning' along a peptide, Alanine's side chain is much smaller than Arginine's, etc, and it's hard to see how molecular recognition could deal with this constantly varying scale. There is also a variety of moieties to deal with - charged here, hydrophobic there, etc. Again, hard to envisage a 'generalist' enzyme with the capacity to allow passage of all acids, yet still grope around the surface and work out which one it is - let alone one that then uses this info to glue specific triphosphates together.

      Another issue: what would be the selective advantage? As soon as you have reverse-translated a given protein into the genome, you and your descendants have the means (assuming, of course, that 'normal' translation occurs) to generate this protein in its millions. You'd never need to reverse-translate that protein again, rendering selection for this capacity weak-to-non-existent.

      And how to distinguish the proteins one has not got in one's genome from those one has?

    10. Yes can't think of a good reason for it I guess, certainly not as a means of acquiring new genes, that's for sure. Great, thanks.

    11. Well Allan, we don't actually have to envision a scanning enzyme to explain how reverse translation could happen. The way translation takes place doesn't involve scanning mRNA either. mRNA isn's so much "read" as it sort of "accepts" corresponding tRNA anticodons. So the translation happens through the tRNA-mRNA codon-anticodon complementarity. The ribosome basically just holds it all in place, shuffles the tRNA's through and catalyzes the peptide bond formation.

      One could imagine a kind of translation running in reverse, with the protein playing the role of mRNA, an intermediate structural bridge ala tRNA (let's call them reverse-tRNA), with multiple such reverse-tRNA's, at least one for every amino acid. Then on the other end of these tRNA's would still sit the anticodon binding site. The reverse-ribosome then functions as an RNA ligase, being fed RNA bases in through an opening such that they can base-pair with the anti-codon of the reverse-tRNA, and the reverse-ribosome subsequently ligating them together into an RNA chain.

      This is of course wild, unfettered speculation. I don't believe something like this ever happened or existed. I don't even know if the chemistry is feasible. My aim was merely to point out that we can at least concieve of ways in which reverse translation could function without having to include scanning enzymes. Mostly because of the way translation actually happens, there's no scanning enzyme involved there either afaik.

    12. Yes, I guess 'scanning' is properly a multi-component affair.

      Nonetheless, the 'reverse-ribosome' has a much rougher 'edge' to traverse. The hole through which the peptide is fed would need to be large enough to accommodate the largest amino acid. A primitive system reverse-translating only glycine would struggle to permit much else through, for example, and the range of chemical properties and binding energies serially encountered in any multi-acid system would also be a challenge.

  6. The article in Evolution News & Views states: "Because RNA has more degrees of freedom, it can take on a wide variety of forms not possible for DNA." Here the author seems to be thinking of duplex DNA. However, DNA can extrude complex stem-loop structures that can become even more complex when there is strand breakage. The 3 Nature articles are reviewed by Ramos and Laederach (see comments at:
    http://www.nature.com/nature/journal/v505/n7485/full/505621a.html#comments ).

  7. Holy shit Larry- talk about making the wrong inference. There isn't anything in what you quoted that even hints the author didn't know that RNA was a catalyst.

    Unguided evolution cannot explain mRNA. Unguided evolutuon cannot explain lincRNA. Unguided evolution can't explain anything because all it has are appeals to sheer dumb luck.

    Heck can unguided evolution even muster a testable hypotehsis? I think not.

    1. Here's a testable hypothesis: The origin of the genetic code.

      Turns out evolution can explain all those things.

    2. Let's look at the ID explanation:
      Designdidit. Dunno how, dunno when, dunno where. Just blanket "design". Oh wait, it was designed intelligently.

      Any testable predictions? Oh yeah, whatever we observe is what the designer wanted to design. Using the method: Intelligent design.

    3. The IDiots have made another prediction that turned out to be true!

      They predicted that if something looks like it was designed by the Intelligent Designer but it turns out that real scientists can show that it evolved. then it wasn't really designed in the first place.