The ENCODE delusion


I can take it no more. I wanted to dig deeper into the good stuff done by the ENCODE consortium, and have been working my way through some of the papers (not an easy thing, either: I have a very high workload this term), but then I saw this declaration from the Electronic Frontier Foundation.

On September 19, the Ninth Circuit is set to hear new arguments in Haskell v. Harris, a case challenging California’s warrantless DNA collection program. Today EFF asked the court to consider ground-breaking new research that confirms for the first time that over 80% of our DNA that was once thought to have no function, actually plays a critical role in controlling how our cells, tissue and organs behave.

I am sympathetic to the cause the EFF is fighting for: they are opposing casual DNA sampling from arrestees as a violation of privacy, and it is. The forensic DNA tests done by police forces, however, do not involve sequencing the DNA, but only look at the arrangement of known variable stretches of repetitive DNA by looking at just the length of fragments cut by site-specific enzymes; they can indicate familial and even to some degree ethnic relationships, but not, as the EFF further claims, “behavioral tendencies and sexual orientation”. Furthermore, the claim that 80% of our genome has critical functional roles is outrageously bad science.

This hurts because I support the legal right to genetic privacy, and the EFF is trying to support it in court with hype and noise; their opposition should be able to easily find swarms of scientists who will demolish that argument, and any scientifically knowledgeable judge should be able to see right through the exaggerations (maybe they’re hoping for an ignorant judge?). That conclusion, that 80% of the genome is critical to function, is simply false, and it’s the notorious dishonest heart of ENCODE’s conclusions.

And then there is this lovely little commercial for ENCODE, narrated by Tim Minchin, and portraying ENCODE as a giant cancer-fighting robot.

Oh, jebus…that was terrible and cringeworthy. Not just the ridiculous exaggerations … the Human Genome Project also claimed that it would provide the answers to all of human disease, as has, to a lesser degree, most every biomedical grant proposal, it seems — but that they invested in some top-notch voice talent and professional animation to promote some fundamentally esoteric science to the general public as a magic bullet…I mean, robot.

Scientists, don’t do this. Do make the effort to communicate your work to the public, but don’t do it by talking down to them and by portraying your work in a way that is fundamentally dishonest and misleading. If you watch that video, ask yourself afterward: if I hadn’t read any of the background on that project, would I have the slightest idea what ENCODE was about from that cartoon? There was no usable information in there at all.

So what is ENCODE, actually? The name stands for Encyclopedia of DNA Elements, and it’s the next step beyond the Human Genome Project. The HGP assembled a raw map of the genome, a stream of As and Gs and Cs and Ts, and dumped it in our lap and told us that now we have to figure out what it means. ENCODE attempts to break down that stream, reading it bit by bit, and identifying what each piece does; this part binds to a histone, for instance, or this chunk is acetylated in kidney cells, or this bit is a switch to turn expression of Gene X off or on. It tries to identify which genes are active or inactive in various cell types. It goes beyond the canonical sequence to look at variation between individuals and cell types. It identifies particular genetic sequences associated with Crohn’s Disease or Multiple Sclerosis or that are modified in specific kinds of cancers.

ENCODE also looks at other species and does evolutionary comparisons. We can identify sequences that show signs of selection within the mammals, for instance, and ENCODE then maps those sequences onto proposed functions.

You know what? This is really cool and important stuff, and I’m genuinely glad it’s being done. It’s going to be incredibly useful information. But there are some unfortunate realities that have to be dealt with.

It’s also drop-dead boring stuff.

I remember my father showing me a pile of maintenance manuals for some specific aircraft at a Boeing plant when I was a kid; these were terrifyingly detailed, massive books that broke down, bit by bit, exactly what parts were present in each sub-assembly, how to inspect, remove, replace, repair, and maintain a tire on the landing gear, for instance. It’s all important and essential, but…you wouldn’t read it for fun. When you had a chore to do, you’d pull up the relevant reference and be grateful for it.

That’s ENCODE. It’s a gigantic project to build a reference manual for the genome, and the papers describing it are godawful tedious exercises in straining to reduce a massive data set to a digestible message using statistics and arrays of multicolored data visualization techniques that will give you massive headaches just looking at them. That is the nature of the beast. It is, by necessity and definition, a huge reference work, not a story. It is the antithesis of that animated cartoon.

I’m uncomfortable with the inappropriate PR. The data density of the results makes reading the work a hard slog…but that’s the price you have to pay for the volume of information delivered. But then…disaster: a misstep so severe, it makes me mistrust the entire data set — not only are the papers dense, but I have no confidence in the interpretations of the authors (which, I know, is terribly unfair, because there are hundreds of investigators behind this project, and it’s the bizarre interpretations of the lead that taints the whole).

I refer to the third sentence of the abstract of the initial overview paper published in Nature; the first big razzle-dazzle piece of information the leaders of the project want us to take home from the work. That 80%:

These data enabled us to assign biochemical functions for 80% of the genome.

Bullshit.

Read on into the text and you discover how they came to this startling conclusion:

The vast majority (80.4%) of the human genome participates in at least one biochemical RNA- and/or chromatin-associated event in at least one cell type.

That isn’t function. That isn’t even close. And it’s a million light years away from “a critical role in controlling how our cells, tissue and organs behave”. All that says is that any one bit of DNA is going to have something bound to it at some point in some cell in the human body, or may even be transcribed. This isn’t just a loose and liberal definition of “function”, it’s an utterly useless one.

Now this is all anyone talks about when describing this research: that it has found a ‘function’ for nearly all of human DNA (not true, and not supported by their data at all) and that it spells the demise of junk DNA, also not true. We know, for example, that over 50% of the human genome has a known origin as transposable elements, and that those sequences are basically parasitic, and has no recognizable effect on the phenotype of the individual.

I don’t understand at all what was going through the head of the author of that paper. Here’s this awesome body of work he’s trying to summarize, he’s representing a massive consortium of people, and instead of focusing on the useful, if rather dry, data the work generated, he decides to hang it all on the sensationalist cross of opposing the junk DNA concept and making an extravagant and unwarranted claim of 80 going on 100% functionality for the entire genome.

Well, we can at least get a glimpse of what’s going on in that head: Ewan Birney has a blog. It ended up confusing me worse than the paper.

For instance, he has a Q&A in which he discusses some of the controversy.

Q. Hmmm. Let’s move onto the science. I don’t buy that 80% of the genome is functional.
A. It’s clear that 80% of the genome has a specific biochemical activity – whatever that might be. This question hinges on the word “functional” so let’s try to tackle this first. Like many English language words, “functional” is a very useful but context-dependent word. Does a “functional element” in the genome mean something that changes a biochemical property of the cell (i.e., if the sequence was not here, the biochemistry would be different) or is it something that changes a phenotypically observable trait that affects the whole organism? At their limits (considering all the biochemical activities being a phenotype), these two definitions merge. Having spent a long time thinking about and discussing this, not a single definition of “functional” works for all conversations. We have to be precise about the context. Pragmatically, in ENCODE we define our criteria as “specific biochemical activity” – for example, an assay that identifies a series of bases. This is not the entire genome (so, for example, things like “having a phosphodiester bond” would not qualify). We then subset this into different classes of assay; in decreasing order of coverage these are: RNA, “broad” histone modifications, “narrow” histone modifications, DNaseI hypersensitive sites, Transcription Factor ChIP-seq peaks, DNaseI Footprints, Transcription Factor bound motifs, and finally Exons.

Oh, jeez, straining over definitions—ultimately, what he ends up doing is redefining “functional” to not mean functional at all, but to mean simply anything that their set of biochemical assays can measure. It would have been far more sensible to use a less semantically over-loaded word or phrase (like “specific biochemical activity”) than to court confusion by charging into a scientific debate about functionality that he barely seems to comprehend. It would have also conformed to the goals he claims to have wanted to achieve with public education.

ENCODE also had the chance of making our results comprehensible to the general public: those who fund the work (the taxpayers) and those who may benefit from these discoveries in the future. To do this we needed to reach out to journalists and help them create engaging stories for their readers and viewers, not for the readers of Nature or Science. For me, the driving concern was to avoid over-hyping the medical applications, and to emphasize that ENCODE is providing a foundational resource akin to the human genome.

Uh, “giant cancer-fighting robot”, anyone? Ewan Birney’s name is right there in the credits to that monument to over-hyping the medical applications.

I’ll be blunt. I don’t think Birney has a clue about the biology. So much of what he has said about this project sounds human-centered and biased towards gross misconceptions about our place in biology. “We are the most complex things we know about,” he says, and seems to think that there is a hierarchy of complexity that correlates with the phylogenetic series leading to humans, where, for instance, fugu are irrelevant to the argument because they’re not a mammal. This is all nonsense. I would not be at all surprised to learn that the complexity of the teleost genome is significantly greater than that of the tetrapod genome; and there’s nothing more complex about our genetics than that of a mouse. I get the impression of an extremely skilled technologist with almost certainly some excellent organizational skills, who is completely out of his depth on the broader conceptual issues of modern biology. And also, someone who is a total media disaster.

But I’m just a guy with a blog.

There is a mountain of material on ENCODE on the web right now — I’ve come late to the table. Here are a few reading recommendations:

Larry Moran has been on top of it all from day one, and has been cataloging not just the scientific arguments against ENCODE’s over-interpretation, but some of the ridiculous enthusiasm for bad science by creationists.

T. Ryan Gregory has also been regularly commenting on the controversy, and has been confronting those who claim junk DNA is dead with the evidence: if organisms use 100% of their genome, why do salamanders have 40 times as much as we do, and fugu eight times less?

Read Sean Eddy for one of the best summaries of junk DNA and how ENCODE hasn’t put a dent in it. Telling point: a random DNA sequence inserted into the human genome would meet ENCODE’s definition of “functional”.

Seth Mnookin has a pithy but thoughtful summary, and John Timmer, as usual, marshals the key evidence and makes a comprehensible overview.

Mike White summarizes the ENCODE projects abject media failure. If one of Birney’s goals was to make ENCODE “comprehensible to the general public”, I can’t imagine a better example of a colossal catastrophe. Not only does the public and media fail to understand what ENCODE was about, but they’ve instead grasped only the completely erroneous misinterpretation that Birney put front and center in his summary.

You’ll be hearing much more about ENCODE in the future, and unfortunately it will be less about the power of the work and more about the sensationalistic and misleading interpretation. The creationists are overjoyed, and regard Birney’s bogus claims about the data as a vindication of their belief that every scrap of the genome is flawlessly designed.

Comments

  1. says

    The silliness of the misuse of ENCODE data does far further than just the EFF puffing up a case that shouldn’t really need to be puffed up. Mindless blowhard Mike Egnor has been trumpeting the “80% functional” figure for the last week or so as evidence in favor of intelligent design. He’s been told repeatedly that “function” as used by the ENCODE people is not really “function” in the sense that anyone else would use it, but that doesn’t matter to him. Junk DNA has a “function” so it must be designed.

    Expect to see ENCODE trumpeted loudly by Discovery Institute shills and loony YEC’s from now on. That it doesn’t actually support their cause matters not, someone mislabeled something, and now it will be taken as Gospel evidence for intentional design (pun intended).

  2. yubal says

    PZ,

    What would you consider to be functional?

    Just asking because I know a whole set of people who work on unfolded proteins and all those proteins do is binding other molecules. The best I’ve ever seen is low affinity medium specificity binding from that class of proteins.

    You can mutate the crap out of those unfolded proteins without loss of binding, only very specific mutations can change the “function” of those protein, resulting in a decrease or increase of binding. They make up around 15% of all translated gene information in humans and all they do is to stick the catalytically active stuff together in a concentration dependent manner for a limmited amount of time. In a kinetic way, not in a structural specific manner. Some people told me their function is to serve as a mutational sink, so the genome can “eat mutations” and therefore reduce the risk of damage to the structural RNA/protein fraction. Nonsense from my point of view, increasing the junk pool would be a way more cost effective way to reduce the occurrence of random mutations in coding regions. I’ve also seen people working on unorganized RNAs that do nothing else than binding other stuff.

    This year, I’ve attended a conference where a young scientist presented his finding of several thousand hammerhead ribozyme sequences in 5’UTRs of LINE’s and other regions outside the encoding fraction of our genome. Some were found to be active. What is going on there? According to his findings they can even make protein in the absence of an ATG codon when a ribozyme is inserted in the 5’UTR. Not exactly my field and probably not mature for publication yet, but there are indications for activity in those regions. What it means and how much impact on the cell it might have is subject to more research, as always. A good question would be e.g. how the Fugu got rid of its non-cncoding regions and what does that mean for the Fugu compared to related species. Is that a benefit (less genome to maintain) or sometimes disadvantageous (loss of a specific function) or doesn’t it matter at all?

  3. Amphiox says

    So you have this big pile of junk in your backyard, and it doesn’t seem to do anything. Then one day you notice that, ever so slightly, it smells. And then you examine the pile in detail, and you find over 80% of the individual pieces of junk in the pile smell. So the junk has activity, it is doing something to make the smell.

    80% of it or more!

    Wow!

    It’s still junk.

  4. A. R says

    The worst part for me? One of our genetics faculty has fallen for the bullshit without reading the paper. I shall have to educate him when I have the chance.

  5. mothra says

    When ENCODE uses ‘function’ in their own peculiar way and other scientists must explain, we have the obverse of the creationist general use of the word ‘theory’ versus the specific scientific meaning of that term. Good science is then placed on the defensive and the general public will only see competing narratives- which is a bogus interpretation of reality shared by creationists in particular and republicans in general.

  6. unclefrogy says

    I guess this would be one place to ask a question but pardon if it is not stated as a proper question.
    I have read about junk DNA and while I was reading this post a thought occurred not always a reliable sign of truth. I thought about molecular receptors it is the active part the part of the molecule that fits the receptor that is definitive the rest of the molecule is mostly inactive correct. Is that what is going on with DNA and the problem is to identify the active parts and what they do. What key/lock functions they work on or are used in and how they do that.
    It has been a long time since I did any active studying this level and just wonder if I am looking in the wrong direction.

    uncle frogy

  7. Amphiox says

    I thought about molecular receptors it is the active part the part of the molecule that fits the receptor that is definitive the rest of the molecule is mostly inactive correct.

    I would not say that.

    The sequence of the protein outside of the active site determines, through the various interactions between the amino acids, how the protein folds into its three dimensional shape, and it is the three dimensional shape that makes the active site work.

    Also, in terms of biological function, it is not always just the single active site that matters. There are usually other regions of the protein that bind to other things, for regulator purposes.

    In the case of receptors (as opposed to catalysts in which the active site is responsible for the reaction) a signal needs to be transduced to effect the function. So after the receptor binds its target, something else must happen (usually a change in the shape of the protein, which affects is binding to another protein, or its ability to catalyze a specific reaction), and it is this something else that passes the signal on. That of course means that most receptors need at least two “active” sites, one to bind the signal, and one to pass on the signal.

    The most accurate analogy, if you want to compare a protein to a genome, would be any region of the protein sequence that can be changed (mutated) without changing the protein’s function. Such a region would be analogous to non-functional DNA.

  8. says

    I’ve been waiting for you to help me makes some sense of all this. Thank you, and I hope you’ll have more on this subject later.
    BTW: Were you missing from this month’s Free Inquiry? I looked, but didn’t find.

  9. yubal says

    unclefrogy,

    I thought about molecular receptors it is the active part the part of the molecule that fits the receptor that is definitive the rest of the molecule is mostly inactive correct.

    I do not understand that question.

    In general, receptors display a certain effective binding area that allows for specific binding of one narrow kind of chemistry. Signal transduction is then carried out by rearrangements of the receptor, resulting in specific binding and processing of an effector molecule (or else, there is more to it than just that).

    You need to maintain the recognition surface and also the transition domains plus the effector activation areas. Else you lose or decrease the signal transduction of the receptor. This can sometimes be desired, usually it is not. Some mutations result in gain of function, which can also be adverse or desirable, depending on the context.

    DNA has usually NOTHING to do with that. DNA is the substrate of molecular function and only very very rarely active by itself. DNA is carrying information, selection acts on proper RNA/Protein/Tissue/Cell/Organ/Organism-function, not on the DNA itself. The property of genes is to be less likely to be inherited into subsequent generations when the information it encodes for is less suitable for the selective pressures than alternate information within the same genetic pool. Genes are what we can trace, selection is upon function of the gene products. You can inherit any nonsense gene as long it is complemented by a working version or not selected for or silenced or whatever.

  10. robro says

    PZ: Thanks for covering this and providing other references. I saw the “80% isn’t junk” story around the news a few days ago and wondered what the back story might be.

  11. says

    Nailed it! It’s even more annoying that it’s already in the courts! I had convinced myself that the misinformation wouldn’t matter much — creationists are wrong about things anyway, most people aren’t experts who need to know what percentage functionality is correct — but, ugh, if legal decisions rely on this, that’s bad.

  12. says

    Thanks for the great summary, PZ.

    So, Ewan Birney’s reasoning for using the word “functional” was basically “it doesn’t have a consistent definition, so I’m going to define it to mean whatever I want so I can sound important.” Seriously, if being an English major has taught me anything, it’s that words have both denotative and connotative value, and that both are important when deciding which word best suits your purpose. Thanks to Birney’s linguistic fuckery, we now have to spend the next 20 years listening to intelligent design apologists use his words to argue that God intelligently designed DNA. Thanks a lot, asshole.

    Oh PZ, I just want to add that watching the video of your lecture (I can’t remember where you gave it) that explained all the different kinds of junk DNA has really helped me understand this whole situation. So, thank you for that.

  13. Aylwyn Scally says

    Seriously, who gives a toss what the creationists think about this? How is it relevant that they are going to misunderstand this issue just they do every other one? By all means let’s have a robust scientific discussion – and even a discussion about the broader relevance of this research, but we shouldn’t be holding scientists responsible for whatever new delusions those unfortunate people afflict themselves with.

  14. says

    As so often happens, bad science reporting got going early. When scientists use short hand terms among themselves, the reporters often push those out to the public with completely wrong associations. We do have “junk” in our DNA from retrovirus inclusion and segments that did code for proteins in our ancestors but are not activated or are broken in us (such as our enzyme that made vitamin-C for them but is defective for us). However, we don’t know how much junk there is because we don’t know how much of the DNA makes RNA for control or other functions (and how much of that is broken, as well).

  15. txpiper says

    I figured the reaction to the ENCODE conclusions would be like someone showing real numbers in regards to the federal budget deficit/national debt. It just irritates the folks who didn’t want to hear about it.

  16. says

    Obviously fugu has less cause its just a stupid fish and salamanders have more cause they need to tap into elemental fire! It’s so obvious ;p

  17. yubal says

    What strikes me, again, is that almost everyone seeks to find a possible functionality of junk DNA by analyzing its sequence.

    DNA is a polymer and the primary property of bio-polymers is to exclude solvent accessible volume. Who says it has to encode for anything in order to have a biological function? Because it happens to be DNA?

    Junk DNA can as well serve simply as filling material to generate a “correct” telomer to centromer distance to mass ratio of the chromosomes in order to be processed by the spindle apparatus? Just one plausible scenario I just thought of. There are many others. A chromosome is in the first place a huge chunk of molecules and not simply an information storage container. Is anyone even looking for other properties of junk DNA than its encoding potential? A straight forward but also pain-in-the-ass experiment would be to systematically delete an increasing number of non-coding regions from one to all chromosomes and to analyze the phenotypes of the model system. I’d say Drosophila should be a suitable system for that kind of experiment.

    (People tend to look for the lost set of keys under the street-light because there is enough light and not because it was lost under the street light.)

  18. Amphiox says

    yubal, if the function of junk DNA is not sequence specific, the sequence of it still requires explanation. Why are the sequences of different portions of the junk DNA different? Why do different species have differing sequences? Why is it not just a string of A’s or G’s or whatnot, if sequence does not matter?

    And if it has a structural role why the vast differences in amounts between closely related species?

  19. Amphiox says

    Oh look, the liar texpip has jumped threads again with more contentless fapping.

    Notice how it completely ignores the entire substance of the original post in order to make its pathetic attempt at a snark?

    Intellectual dishonesty all the way down.

  20. Amphiox says

    The ENCODE press release is akin to releasing an unemployment rare of zero by redefining the word “job” to include breathing.

  21. Nerd of Redhead, Dances OM Trolls says

    I figured the reaction to the ENCODE conclusions would be like someone showing real numbers in regards to the federal budget deficit/national debt.

    Gee, and we figure anything you say is nothing but fuckwitted presuppositional OPINION without evidence. And you never, ever fail that. Where is your evidence for your imaginary creator, or that your babble is anything other than mythology fiction? Gee, YOU ALWAYS FAIL TO PROVIDE CONCLUSIVE PHYSICAL EVIDENCE FOR YOUR PRESUPPOSITIONS LIKE YOU ARE NOTHING BUT AN INCOHERENT DELUSIONAL FOOL. And you never, ever, fail to prove that evidenced based conclusion. Unlike anything you OPINE….

  22. yubal says

    if the function of junk DNA is not sequence specific, the sequence of it still requires explanation.

    Why? The question is it “sequence specific” or not.

    Why are the sequences of different portions of the junk DNA different?

    Well, for most LINEs they are pretty much similar and we know roughly why. And anyways, why should they be the same?

    Why do different species have differing sequences?

    A) Do they have different sequences? I don’t know what the overall similarity scores of junk are but some DNA retrotransposons are defiantly alike across species. That’s what we use to demonstrate common ancestry after all.

    B) Why should that be an issue? If sequence doesn’t matter it is open for mutation without selection.

    Why is it not just a string of A’s or G’s or whatnot, if sequence does not matter?

    Actually it is more common to have trinucleotide repeats than singlenucleotide repeats. But yes, a poly G would have an amazingly tiny informational entropy, whatever that would imply to a cell. Just go ahead and replace a a, let’s say, 3500bp stretch of junk DNA with a 3500bp poly G and let us know what happens.

    And if it has a structural role why the vast differences in amounts between closely related species?

    Closely related species have a separate history of junk acquisition/translocation. The closer related the more they should match.

    Mutations always work on preexisting conditions. “If” there would be a structural role of the junk DNA on the fidelity of cell division, the cell division machinery would be optimized for that size by natural selection. It is easier for the species to adopt their cell division machinery to the size of the junk than to identify junk regions and cleave them in order to match the optimum of the cell division machinery.

    And yes, this was an hypothetical example. There is actually no reason to discuss that any further. It serves as an example for the notion that other reasons than base pair sequence could account for junk DNA to be functional.

    Narrow it down by looking at the Fugu and other species that fall out of the “normal” 80% junk ratio. If you just look at sequences you introduce a systematic bias, that was all I was saying.

  23. WhiteHatLurker says

    TL;DR

    What does the amount of (for lack of imagination to think of a more applicable word) active DNA have to do with laws around collection of same?

  24. Amphiox says

    re: Yubal @25;

    Thanks for those answers, but actually I knew all that. My questions were rhetorical.

    The point I was making is that the specific sequences of the junk DNA are an observed feature that requires an explanation.

    To propose that the DNA has a structural function does not provide that explanation, since any DNA of any sequence could serve to provide the same structural function.

    Thus the proposition that junk DNA has a structural function does not answer the question of “Why does this junk DNA have this sequence X, and not this other hypothetical sequence Y?”

    It is because we are interested in answering this question that we continue to discuss the sequences of junk DNA when we study it.

    The potential explanations could be:

    1. The specific sequence has function, and is thus preserved/promoted by natural selection.

    2. The specific sequence has no function, and is just a random string.

    3. The specific sequence has no function, and is the result of historical contingency.

    If 1, of course, then the DNA is not junk. But if either 2 or 3, the DNA can still be “junk” even if it actually does have a structural role. The sequence itself, rather than the DNA, is the junk.

  25. Amphiox says

    Keep in mind that fugu, as an eukaryote, although it may have less “junk” DNA than other eukaryotes, still has plenty of junk DNA, as all eukaryotes have substantial junk DNA.

    If you want an organism that has no junk DNA, you have to look at bacteria.

  26. Amphiox says

    I figured the reaction to the ENCODE conclusions would be like someone showing real numbers in regards to the federal budget deficit/national debt.

    Nope. It is like someone showing fake numbers regarding the national deficit/national debt, derived by redefining, without justification, what “deficit”, “debt”, “budget”, and “federal” actually mean.

    It just irritates the folks who didn’t want to hear about it.

    It irritates people who are honest and care about honest communication.

    It’s not surprising that it does not irritate the texpip, since the texpip is a liar.

  27. yubal says

    Amphiox,

    I don’t think that is mutually exclusive.

    We already know that a good deal of the junk fraction comes from viral sources which explains many of the sequences we see and we know that some of them still have a certain function which is also why the cell shuts them down most of the time.

    So, it can be both, encoding and structural the same time and neither would truly be junk. Anything might have a certain valid benefit for the cell, the sequence, the structure or junk promoted discontinuity of the encoding regions that help regulate them, or..or…or..

    and yes, I doubt junk DNA sequences have a significant influence on the cell unless they get at least translated to the RNA level, but that’s just my personal bias.

    Standard procedure would still be, cut it out and see what happens. If nothing happens it is “true junk”.

  28. JAL: Snark, Sarcasm & Bitterness says

    The ENCODE press release is akin to releasing an unemployment rare of zero by redefining the word “job” to include breathing.

    I literally lol’d at this. XD I’ll always think of this when ENCODE comes up.

    I love how much fun I have learning here.

  29. Amphiox says

    So, it can be both, encoding and structural the same time and neither would truly be junk. Anything might have a certain valid benefit for the cell, the sequence, the structure or junk promoted discontinuity of the encoding regions that help regulate them, or..or…or..

    There are examples of junk DNA that has regulatory or other functions – examples of parasitic repeats, or decayed pseudogenes that were later repurposed. The antifreeze genes in some icefish are an example. They started as pseudogenes of digestive enzymes, duplications decayed into non-functional remnants that, much later, got re-expressed and became genes again, with a wholly new function.

    I suspect that if any of the non-coding DNA has structural function, it will be of the same sort. Non-functional DNA later repurposed through contingent evolutionary opportunity, as evolution can only exploit such DNA for structural purposes if it is already there.

    Just because it has function doesn’t mean it isn’t, or wasn’t “junk”.

    Introns as well are probably of this type. Sequences that when they first arose were non-functional (in this case, early in the history of eukaryotes when an infection of parasitic DNA, likely a consequence of the initial endosymbiosis event, ended up chopping many of the host’s genes into pieces) but later in some cases repurposed for regulatory functions (such as allowing of differential splicing).

  30. yubal says

    Well, yes, there might be a certain fraction of silenced genes or duplicated silenced genes around in the genome. Actually, there HAS to be. This is exactly the same mechanism what we assume the Rad51 paralogues originated from, a RecA-like ancestral gene that was duplicated, silenced and mutated until the mutated copies gained a desirable function. Note that there is NO organism known to date that carries two copies of the same RecA-like gene. That stuff is heavily selected against. Metabolic genes however may be present in many identical copies.

    Unfortunately for the case of junk DNA, we would be easily able to spot them based on their sequence resemblance to known genes. I have no idea how much the contribution of those silenced genes is to the total volume of “junk DNA”, but I suspect it is much less than 5%.

    I’ve seen Bacteriopohage genes that have no function whatsoever. Residing in alternate reading frames, frame shifts, isolated, but with no evidence on the RNA or protein level, but ridiculously well expressed and folded when subcloned. Genes you can delete without ANY phenotype, genes without ANY function we are capable to detect or understand, but the stuff persists well conserved over and over again on the most compressed and efficiently organized genomes we ever found. Phages even use alternate ORFs to encode for totally different genes on the same stretch of DNA, that is a mind blowing efficiency of information compression after several billion years of evolution. If you want to blow your mind, browse through the coding regions of some bacteriophages, you’ll find base-pairs that are involved in at least three genes at the same time. Genes that are actually evidently expressed. Those Phages aren’t even alive, but they still carry totally unnecessary genes close to ORFs of crucial gene products. And we just can’t tell why or at least get a grasp what they might do. Why is that extreme compression of information in one region and then the blunt useless insertion of one totally unnecessary gene right in between? And we are talking the most minimal genome known to mankind here. The majority of those gene products seems to be four alpha helical bundles and some two or four anti parallel beta strands based on secondary structure prediction. Even Bacteria carry “junk” although to a much lower extent than Eukarya. Let alone their Phages.

    Quintessentially, I think we are far further away from understanding the framework of inheritance than we make ourselves believe. 100 years ago people actually thought proteins carry the genetic information. Just because DNA couldn’t ever be complex enough to store it. (Linus Pauling, you were WRONG)

    This stuff is still hot as hell, let’s see who finds the next piece of the puzzle.

  31. Amphiox says

    If the sequence is in fact strongly conserved then I think the null hypothesis must be that the sequence itself has functional significance, even if we can’t yet figure out what it is. Because only purifying selection can maintain a conserved sequence in that manner against the steady attrition of the background mutation rate.

    Therefore, at least to me, if a sequence is found to be strongly conserved, then it isn’t junk even if we don’t yet know what function it has. A definitional characteristic of “junk” DNA has to be that its mutation rate must approach that of the background, indicating that its sequence has minimal functional role and is therefore mostly invisible to selection.

    But in the case of bacteriophages with multiple reading frames, I would hypothesize that strong selection pressure to preserve the gene on any one of the reading frames may well be enough to preserve the genes on the other reading frames, since such pressure will, automatically, conserve the entire sequence. If at one point the phage evolved multiple genes on different reading frames, but later found itself in an environment where one of those genes isn’t necessary any more, it may end up losing the ability to transcribe that one gene, but the sequence of that gene will continue to be preserved because the sequences of the other genes in the same stretch of DNA, but with different reading frames, are preserved, such that we would retain the ability to read and recognize that “dead” gene and even re-express it in experiments.

    I do not think we can call that stretch of DNA “junk” DNA however, as it still has function in the other genes it expresses. We could potentially call that knocked gene a “junk” gene, or perhaps a variant of viral pseudogene.

  32. Amphiox says

    Archaea have introns in some of their genes, IIRC, but as far as I know, bacteria generally do not.

    It would be interesting to see if there are any bacteria out there that truly have absolutely no non-functional DNA. A good place to investigate might be bacteria with stripped down, minimal genomes, like mycoplasmas, or bacteria with very fast usual replication times (where the burden of transcribing extra DNA would be particularly detrimental in terms of slowing down replication).

  33. Holms says

    On September 19, the Ninth Circuit is set to hear new arguments in Haskell v. Harris, a case challenging California’s warrantless DNA collection program. Today EFF asked the court to consider ground-breaking new research that confirms for the first time that over 80% of our DNA that was once thought to have no function, actually plays a critical role in controlling how our cells, tissue and organs behave.

    I’m having trouble seeing connection here. Are they trying to say that the percentage of our DNA that ‘plays a critical role in etc.’ is the determining factor for whether DNA collection is justifiable?

    I’m trying to picture this playing out in a court somewhere. “We the jury find the LAPD not guilty of violating the privacy of Mr. Soandso, because not enough DNA is actually functional thus he doesn’t have any privacy to violate in the first place. Or something.”

    I note from the linked article:

    This research comes out of a gigantic nine-year, federally-sponsored, world-wide project called ENCODE (Encyclopedia Of DNA Elements), which was designed to learn more about “junk” DNA. These research findings should have broad ramifications for federal and state DNA collection programs.

    Why? Why the fuck is our right to privacy dependant on our genetics? The article responds to this query:

    However, the ENCODE research reinforces the points we’ve made multiple times before—that DNA—whether it is in the form of a full genetic sample or an extracted profile—can reveal an extraordinary amount of private information about you, including [a bunch of private stuff].

    The first thing I did here was some heavy facepalming when I realised my flippant jury statement above was actually quite close to the argument being made. My beef with it is that such an argument rests on the premise that the only thing relevant to this act is privacy, completely ignoring our even more fundamental right to bodily autonomy. We reject forced surgery – even if it is life-saving – on this basis; privacy, while an important right, does not enter the equation here.

    Forced DNA collection is unconstitutional even if it does not violate privacy; it is a violation of autonomy in either case.

    As for the incidental matter of that corny cartoon, it seems to be fairly typical for any scientific outreach aimed at the public that it will be as patronising as possible. British climate science cartoons are cloying to the point of suffocation, and that ‘science for fashion-obsessed women’ ad was downright nauseating.

    An open message to all science outreach organisations: STOP FUCKING UP THE MESSAGE.

  34. says

    @Aylwyn Scally,

    Seriously, who gives a toss what the creationists think about this?

    It’s not just the creationists, a friend of mine runs his own evangelical ‘ministry’ in the UK including shouting from street corners. I’m glad PZ has given this summary as he recently posted on his facebook page ->

    One more blow to atheists – Junk DNA not junk afterall

    No idea what the ‘blow’ is as he has blocked me from Facebook – he doesn’t like dissent on his assertions – but he has a degree in biochemistry so he will be able to couch his arguments in sciency sounding fluff. This bad science is going to be used by theists to prove a point. When the gullible can look online and see bad science accepted as fact by some and rejected by others then it drives a wedge into their acceptance of the scientific view. The pandering to the media by some scientists or institutions does little to promote general understanding of science and lets theists in to undermine it.

  35. ChasCPeterson says

    If one of Birney’s goals was to make ENCODE “comprehensible to the general public”

    I’d bet that such ‘outreach’ is a deliverable for one or more of the federal grants that funded the project. They probably have a decent advertising budget.

  36. rq says

    The right to privacy isn’t dependent on genetics – but the right to genetic privacy, which is the point here, I think, can be…
    As PZ said, forensic samples aren’t sequenced (although slowly moving into that area, judging from some of the new technology emerging), we look at bits of DNA within the junk DNA that ‘don’t mean anything’ but repeat themselves a measureable number of times. These sections cannot be linked back to your phenotype such as appearance, medical history, etc. (that’s all private information). If I don’t label a profile, I can’t tell anything about that person (besides sex, which in the end, can mean anything). Even the ethnicity is extremely vague and dependent on statistics, and most likely completely inaccurate (without other information).
    In this country, the police DO sample all arrestees, and the reason they are ostensibly allowed to do that is because taking a DNA sample is (now) a non-invasive, easy procedure, and, as mentioned, we only process the bits of DNA that are not direct sources of personal (genetic) information. The lab doesn’t even store the correct reagents for doing anything more specific or complicated.
    I think the genetic privacy issue (with reference to the jury statement in comment #36) can be likened to fingerprints and their use – the bits of DNA used in identification are functionally (so far) meaningless, hence somewhat like fingerprints. They’re a part of you, but they don’t say much about you. They can identify you, but only by comparison to more fingerprints. I can’t take a fingerprint and say it’s yours because it tells me you have brown eyes. Likewise, I can’t take a genetic profile and say it’s a specific person because it shows a particular sexual orientation. For this reason, it (the DNA profile) is not ‘private’ information. It’s a form of ID, like fingerprints or a driver’s license. That’s the idea behind it, anyway.
    I think there’s a lot of fear about misusing the collected samples, and doing more to them than pure identification. And that’s where the genetic privacy issue seems to be made more complicated – if junk DNA previously used only for identification now is functionally relevant, it can tell me things about someone’s biochemistry – and this is now private information, and that makes DNA no longer usable as identification – it provides more information than actually needed to confirm forensically an ID.
    Still thinking about the bodily autonomy issue. Hasn’t been made into an issue here, yet – but then, arrestees have to sign ‘consent’ forms before giving a sample, which is how they get around that little bit… How consensual it all really is, I don’t know. But it’s there officially.

    I enjoyed this post and also the comments by Amphiox and yubal.
    PZ’s video from a while back about junk DNA also helped me immensely in understanding some of the detail. Also, posts like this remind me that reviewing this stuff periodically is good for me.

  37. Steve LaBonne says

    Re #39, I also think that the fingerprint analogy is a sound one, and I have used it in speaking at a training seminar for judges, who seemed to find it helpful. The EFF’s misuse of ENCODE is laughable, but that sort of confusion has unfortunately been around since the advent of forensic DNA testing.

  38. charlessoto says

    I have heard many a biologist describe whatever creature they’re studying as “more highly evolved” than this or that. One even suggested that cephalopods are “more highly evolved than humans.” Which is odd, considering we’ve been evolving exactly as long as they have…

  39. says

    Seems to me that you’re finding offense, PZ, where you shouldn’t be. Long chunks of guardrail and repeated lanes don’t seem to do anything to a road’s function – since they aren’t being ‘used’ and don’t matter if they’re closed or broken at the moment – but that doesn’t mean they aren’t without function and can’t be used to measure odds of coincidental or resultant conditions.

    In other words, you’re arguing over a point which is largely semantical and arguable and a junk statistic that they’re trying, weakly, to debunk, that you would also debunk.

  40. says

    In other words, the data-mining that the EFF is standing against isn’t about whether something i causal, but whether it can be coincidental. Data-miners don’t care which it is if it is able to use it as an identifier.

  41. Amphiox says

    Creationists love to foist the either-or fallacy into the argument, as if any argument against evolution is automatically one for creationism, when that is not the case. With junk DNA they are simply doing the same thing in reverse.

    The functionality of junk DNA is a non-issue for evolutionary theory, in the sense that it is not an empirical test for the theory in a general sense at all. It is merely an observation that the theory explains. Evolution theory has an explanation for both junk DNA that has function (selection for function) and junk DNA that does not (historical contingency and retention of neutral mutations). So it doesn’t actually matter for the validity of evolutionary theory whether junk DNA has or does not have function, or how much has function or which parts have function.

    Creationism, of course, has a big problem with ANY nonfunctional junk DNA. ANY of it, no matter how minor, is empirical evidence AGAINST the design model. This is an issue for creation “theory” not evolution.

  42. Sastra says

    The appeal of the “junk DNA has afunction after all” is going to be much wider than creationism. A lot of well-educated, intelligent people fall for scientific urban legends like “we only know the function of 10% of our brains” because they innately feel that progress was teleologically frontloaded into creation: when we accept our spiritual natures we will be able to finally tap into our potential. The over-extended hype then will appeal to the spiritual. Nature is benevolent — it knows what we will be needing and provides it when necessary.

    I bet this story gets added to the one about how scientists don’t know what 90% of our brain is used for… but it’s ESP!!! Now the genome is going to be involved. If they’re notbusy trying to refute atheists, then they’re busy trying to show how the reductive materialists have got it all wrong. Same difference.

  43. intelligentdesigner says

    Yubal @ 3

    This is what I think: The “non-functional” parts of the gene specify a three-dimensional shape that the translated protein will fold into based upon its hydrophobic and hydrophilic parts. The shape that the protein folds into will affect which molecules the functional parts can interact with (think lock and key). While only very specific mutations will change the function of the protein any mutation that changes the codon to amino acid mapping will change the shape of the folded protein and therefore its ability affect the molecules that it is supposed to interact with. Even mutations that don’t affect the codon to amino acid mapping could create or delete a hair-pin fold in the transcribed RNA that may affect translation. Correct me if I am wrong.

  44. intelligentdesigner says

    Yubal @ 20

    I was thinking that just like the telomere portion of DNA, there may also be similar changes that happen to other parts of the DNA during cell division. These subtle changes in sequence could affect the way the DNA is folded in different cell types. This in turn would affect which genes are exposed for transcription and their three-dimensional proximity to other parts of the DNA which promote or inhibit transcription. Chemical signals from other cells may also affect folding and methalation. Differences in non-coding parts of DNA (like the length of repeated sequences) could affect how long genes are available for transcription and translation and this would account for physical and chemical differences between individuals.

    Diseases that are caused by mutations to non-coding DNA may only affect individuals at the time (measured in cell-divisions) that the mutations affect the way DNA is folded. Mutations that affect individuals in early life would be most likely to be selected out while mutations that affect individuals later in life would accumulate. Also mutations caused by radiation or free radicals may have a delayed affect depending on what part of DNA is damaged.

  45. yubal says

    #47 intelligentdesigner

    Correct me if I am wrong.

    I would love to, but honestly, I have no idea what you were talking about.

    Was that about unfolded proteins?

    They are supposed not to fold at all. Their structure is approximately random within certain boundaries. Only few of them show temporary secondary structures when bound to a target, which is called folding upon binding.

  46. bortedwards says

    Can I just point out that EVERYONE especially (sadly) evolutionary biologists would do well to think about charlessoto post #41?
    The idea of some ‘ladder of progress’ or that cycads are ‘plants from when the dinosaurs were alive’ is screamingly lazy interpretation of evolution at best, and at worst a miscomprehension of the process. And yet a goodly two thirds (educated guess) of CURRENT phylogenetic papers misinterpret such concepts (eg that early branching lineages are somehow ancestral).
    Sorry, off topic, but it would be nice if someone wrote on here about it, PZ? rant over.

  47. yubal says

    bortedwards,

    we are aware that all lifeforms have approximately the same evolutionary age. In an ever changing world, this leads to the arise and decline of species and entire clades. But evolution does not predict there have to be changes when the world remains constant. Look at the Coelacanth again. Those beasties hang around for some 400 Mio. years or so and used to dominate large territories at that time. We find them all over in the fossil record. Today they are confined to small areas in the not-so-deep sea where they live happily. They always found a spot on earth that was quite right for them, although they never made it back to the huge numbers they once had and hence left no fossil record in later times.

    Are the modern Coelacanth higher evolved than the old Coelacanth species? Yes, but only a little bit, they made only very few changes, because they didn’t had to make more in order to prevail. Their cousins back then went through much more hardship and severe changes. They got extremely efficient lungs, feathers, fur, brand new reproductive systems and all that stuff Coelacanth never acquired. Those species are much “higher evolved” than Coelacanth because selection pressure was acting on them more often and much harder.

    Another example are archaebacteria. They still sit around those hot wells and metabolize the chemistry those wells spit out. Their world didn’t change at all, besides the occasional change in mineral output from the well or a new well they could colonize. On the other hand, the archaebacteria we find today are as equally modern as we are. Ancestral lines of all extant species in the evolutionary tree add up to the same length. Archaebacteria are totally up to date with the current environment they are in. It is just that their environment didn’t change that much in the last two billion years.

    It might be just a question of semantics, but “higher evolved” and “more complex” is more or less equal to the amount of selective pressure a species had to undergo in its history. You are higher evolved than an Coelacanth because evolution was acting more often on your line of descent than the Coelacanth line. Your ancestors had to permanently adopt to a changing world or got weeded out, Coelacanth just swam to the next available niche and remained as what it was.

  48. Amphiox says

    The proper term is “more derived”.

    Sticking “complexity” into it confuses the issue, as selective pressure can favor both higher or lower complexity.

    Case in point, who has the more complex hand, Acanthostega, with seven fingers, humans with five, bats with five plus wing membrane, T-Rex with two, or birds with zero?

  49. Rev. BigDumbChimp says

    “intelligentdesigner”

    Who was it from the old blog that used this nym…

    What was his name again?

  50. Amphiox says

    Or consider the duck billed Platypus, poster child for the relatively “less evolved” mammal. It still lays eggs. The females do not have well developed breasts, but instead secrete milk over their skin akin to sweat (transitional based on the hypothesis that mammary glands evolved from modified sweat glands).

    “Primitive”, no?

    Well it also has venomous spurs that inject via a hypodermic mechanism. No other mammal has that.

    And that bill? A stupendously sensitive detector of electromagnetic fields. No other mammal has that, either.

    So whose more “evolved”?

  51. yubal says

    Amphiox,

    No Case in your point.

    You can’t just go ahead and compare extremities to extremities and ask for complexity.

    Increase in complexity is the arise of claws, hands, wings, legs and then leg-fins again out of fins.

    Fins “gained complexity” by changing into different limbs. Limbs that did not exist back in the time where there where only fins.

    But yes, I don’t like that term either, it confuses too many people.

  52. bortedwards says

    Yubal, Just because YOU cannot observe a change between a fossil coelacanth and a living descendant doesn’t mean there has been none. From a coelacanths point of view there is little difference between you and any fossil primate. Your argument that observable complexity begets ‘evolvedness ‘ is dangerously close to the thinking that religious zealots use for sticking humans on top of some fictional biological pile and suggests that there is some pre ordained direction to evolution. There is not. Organisms are evolved to their environments with a contingency on history, but there is no ‘more’ or ‘less’ unless comparing extant with extinct, and then only as ‘from’ and ‘too.’

  53. Amphiox says

    No Case in your point.

    Whut?

    You can’t just go ahead and compare extremities to extremities and ask for complexity.

    Of course I can. What, there’s some rule now that you can’t consider complexity of an organ or organ system but only the entire organism?

    I can talk about the complexity of a car, but not of a steering wheel?

    Who made that up? You?

    Increase in complexity is the arise of claws, hands, wings, legs and then leg-fins again out of fins.

    No, “increase” in complexity is absolutely NOT this. The appearance of novel organ systems and organ types has absolutely nothing directly to do with changes in complexity one way or another. They MAY be associated with more complexity, but they may also not.

    What this is, is an increase in DIVERSITY, not “complexity”.

    Fins “gained complexity” by changing into different limbs.

    No they did not. Absolutely NOT. Fins did not “gain” complexity by changing into limbs.

    At the same time fins were “changing” into limbs, they were also changing into DIFFERENT TYPES OF FINS. And some of those fins are MORE COMPLEX than some of those limbs. And some less so. In fact, fins ARE limbs.

    Limbs diverged into multiple variants. Some became more complex, some became less complex. Among those variants are ones we might call fins. These could be both more or less complex. Other variants are ones we might call arms or legs. These too could be more or less complex.

    Again, this is the process of fins gaining DIVERSITY. At the same time, in a different process, SOME fins gained complexity, but some also lost complexity.

  54. says

    “This isn’t just a loose and liberal definition of “function”, it’s an utterly useless one.”
    I like this line.

  55. intelligentdesigner says

    @49 Kel

    I think it’s fair to say that if there is specific biochemical activity in a section of DNA, even if that activity only occurs for one cell type, it’s probably participating in a function.

    Do it’s wise to keep insisting that any DNA we don’t understand yet is probably junk?

  56. txpiper says

    “From a coelacanths point of view there is little difference between you and any fossil primate.”

    Yeah, they probably play canasta and remark about how we all look alike.
    .
    “Your argument that observable complexity begets ‘evolvedness ‘ is dangerously close”

    Yes…frighteningly close.
    .
    “thinking that religious zealots use for sticking humans on top of some fictional biological pile”

    No kidding. Only an imbecile (sitting at a keyboard) could draw a conclusion like that. What a pompous notion. Given their way, the biological pile would be farming and harvesting us if we hadn’t imposed our arrogant colonialism on the natural world.
    .
    “suggests that there is some pre ordained direction to evolution. There is not.”

    Of course there isn’t. That notion would be way outside of the accepted box. Everybody knows that humans were just big winners in the mutations lottery. Nothing more, nothing less.

    ===

    How can anyone become so screwed up as this? Public education?

  57. Owlmirror says

    “From a coelacanths point of view there is little difference between you and any fossil primate.”

    Yeah, they probably play canasta and remark about how we all look alike.

    [Insert quote from Linnaeus about humans as primates here]

    Given their way, the biological pile would be farming and harvesting us if we hadn’t imposed our arrogant colonialism on the natural world.

    From the perspective of the bacteria and fungi that will consume your flesh when you die, your body is kind of a bumper crop of yummy nutrients.

    Everybody knows that humans were just big winners in the mutations lottery. Nothing more, nothing less.

    As is every other living organism.

    And you know it’s true, because by the premise that big winners in a iterated differential survival-and-reproduction mutation lottery are complex to an unlikely degree, any putative single entity that is infinitely complex and comes from nowhere must be impossible.

    How can anyone become so screwed up as this?

    You’re as screwed up as you are because you are stupid, ignorant, dishonest, and arrogant, and all four attributes feed into each other to prevent you from honestly learning and changing your mind. In short, you’re a kook.

    Public education?

    You’re an ineducable kook.

  58. says

    I think it’s fair to say that if there is specific biochemical activity in a section of DNA, even if that activity only occurs for one cell type, it’s probably participating in a function.

    But if your comment is actually responding to mine (and mine to PZ talking about the misuse of the word function) doesn’t it follow to ask what would be meant by function in that sense? If you found a cog in a car that didn’t seem to be attached to anything yet would spin as the car moved, you don’t say that the cog is functional because you see it spinning. You ask what operation it has to the way the car works.

    If we want to make the additional assumption that since it came from a designer, then since designers have good reasons for things in their designs, we have good reason to think that the cog must do something for the design even in the absence of apparent function (discounting an error in the assembly, or that the structure was a remnant of an earlier design that wasn’t properly purged). But in the case of our biology, the question of whether or not everything that does something does something for the organism is the issue that’s at stake here. What does the evolutionary process demand of our DNA? That seems to be the relevant question…

    Do it’s wise to keep insisting that any DNA we don’t understand yet is probably junk?

    But there’s plenty of DNA we do understand – pseudogenes, for example, being remnants of protein-coding genes where those genes being active in other species that code for particular function.

    Personally, I have no vested interest in whether or not DNA can be classified as junk. The fight over junk seems to matter to ID proponents, but to me it seems about as trivial as arguing for the instances of “good design” nature. It makes sense if you’re trying to make the evidence compatible with an omnipotent designer, as it’s a way of explaining away that which seems at odds with what a master craftsman would build; but it doesn’t advance the notion of an intelligent designer as the question of whether or not a designer intervened is still indistinguishable from the null hypothesis.

  59. txpiper says

    “there’s plenty of DNA we do understand – pseudogenes, for example, being remnants of protein-coding genes…”

    Not always just remnants.

    “we describe the functional relationship between the mRNAs produced by the PTEN tumour suppressor gene and its pseudogene PTENP1 and the critical consequences of this interaction. We find that PTENP1 is biologically active as it can regulate cellular levels of PTEN and exert a growth-suppressive role. We also show that the PTENP1 locus is selectively lost in human cancer. We extended our analysis to other cancer-related genes that possess pseudogenes, such as oncogenic KRAS. We also demonstrate that the transcripts of protein-coding genes such as PTEN are biologically active. These findings attribute a novel biological role to expressed pseudogenes, as they can regulate coding gene expression…”
    http://www.nature.com/nature/journal/v465/n7301/full/nature09144.html

  60. hotshoe says

    “we describe the functional relationship between the mRNAs produced by the PTEN tumour suppressor gene and its pseudogene PTENP1 and the critical consequences of this interaction. We find that PTENP1 is biologically active as it can regulate cellular levels of PTEN and exert a growth-suppressive role. We also show that the PTENP1 locus is selectively lost in human cancer. We extended our analysis to other cancer-related genes that possess pseudogenes, such as oncogenic KRAS. We also demonstrate that the transcripts of protein-coding genes such as PTEN are biologically active. These findings attribute a novel biological role to expressed pseudogenes, as they can regulate coding gene expression…”
    http://www.nature.com/nature/journal/v465/n7301/full/nature09144.html

    So what’s your creationist explanation, txpiper?

    WHY OH MIGHTY MAKER WHY ?

  61. Nerd of Redhead, Dances OM Trolls says

    Still no evidence for your imaginary creator Txpiper, admitted presuppositionalist and delusional godbot. You never, ever show any. Almost like it doesn’t exist….

  62. says

    Not always just remnants.

    This seems like a rehashed version of the vestigial function argument. That pseudogenes are dead genes doesn’t mean they cannot possibly co-opted for any other purpose, but that they are remnants of active genes in other species with disabling mutations gives us a reason to not necessarily think the code must be for another purpose.

  63. Amphiox says

    Not always just remnants.

    Sometimes remnants. Sometimes remnants plus retained vestigial functions. Sometimes remnants plus newly evolved functions.

    But ALWAYS still remnants.

    And always evolved.

    What the dishonest liar texpip again fails to mention is that, according to its “alternative” to evolutionary theory, there should be NONE.

    And yet there they are.

    “Model” falsified.

    *POOF*

    These findings attribute a novel biological role to expressed pseudogenes, as they can regulate coding gene expression…

    Notice how the text explicitly says expressed pseudogenes, because, of course, the distinction must be made with unexpressed pseudogenes which do not have this potential function.

    Notice how the texpip deliberately ignores this to try and dishonestly imply that ALL pseudogenes will have regulatory function.

    Intellectual dishonesty all the way down.

    Notice how the texpip also fails to mention that, of all the multitude of methods available for regulating a given gene, using a pseudogene product to do so is one of the most inefficient, kludgey, and ridiculously wasteful ways imaginable. So why, in the texpip’s “model”, would an all-knowing, all-powerful creator entity (whose own monstrously complex and unlikely existence cannot be explained, only presupposed) choose, out of all the better options available to it, to use this?

    WHY OH MIGHTY MAKER, WHY???

  64. Amphiox says

    Everybody knows that humans were just big winners in the mutations lottery.

    Hamster-wheeling once more to the deliberate misrepresentation of evolutionary theory.

    No, humans were one of MANY winners in the mutations AND SELECTION “lottery”.

    Once again the texpip strawmans evolutionary theory by presenting only part of it and ignoring the other. This time it chooses the “just mutations” lie. Next time it will do the “just selection” lie.

    Never will it ever admit that it is always both, and must always be both.

    To do so, of course, would be to admit that its entire argument is wrong.

    All lies, all the way down.

    Utterly pathetic.

  65. vaiyt says

    Everybody knows that humans were just big winners in the mutations lottery.

    Every extant species is as much of a “winner” as us.

  66. Amphiox says

    we describe the functional relationship between the mRNAs produced by the PTEN tumour suppressor gene and its pseudogene PTENP1 and the critical consequences of this interaction

    The texpip presents evidence that demonstrates that A DUPLICATION MUTATION occurred, and that one copy of that duplication subsequently CHANGED (becoming a pseudogene), after mutating again.

    We find that PTENP1 is biologically active as it can regulate cellular levels of PTEN and exert a growth-suppressive role.

    The texpip additionally presents evidence that this DUPLICATION MUTATION and subsequent MUTATION OF THE COPY has EVOLVED A FUNCTION. That function being to negatively regulate the activity of the original gene. Thus INCREASING THE TOTAL AMOUNT OF BIOLOGICAL INFORMATION IN THE GENOME.

    We also show that the PTENP1 locus is selectively lost in human cancer.

    The texpip additionally presents evidence that this EVOLVED FUNCTION is a BENEFICIAL ONE, since it protects against cancer, and losing it encourages the development of cancer.

    And yet, just in the last thread it was infesting, the texpip was insisting that all the above is impossible, that duplication mutations either cannot occur, if they occur they cannot produce new information and cannot have beneficial effects.

    And thus once more, the pathetic liar texpip is caught shamelessly LYING yet again.

  67. Amphiox says

    We extended our analysis to other cancer-related genes that possess pseudogenes, such as oncogenic KRAS.

    And to top it all off, the texpip presents evidence of evolutionary theory producing a new, TESTABLE HYPOTHESIS, which leads to an advancement in human knowledge, in this case one that may one day contribute to a major improvement in human health and well-being.

    And once again, while science marches on, the texpip’s “alternative” is left drooling dumbly in the corner, babbling nonsense. Useless.

  68. Nerd of Redhead, Dances OM Trolls says

    And once again, while science marches on, the texpip’s “alternative” is left drooling dumbly in the corner, babbling nonsense. Useless.

    Just like Txpiper’s imaginary creator doesn’t exist, and isn’t needed to explain anything. Just as one would expect from a delusional phantasm without any physical evidence for it….

  69. Amphiox says

    Note that PTENP1 works by up-regulating the activity of PTEN, enhancing PTEN’s tumor suppressor gene activity.

    Yep. That’s a duplication mutation that results in a GAIN OF FUNCTION.

  70. Amphiox says

    From the texpip’s link (figure caption):

    Working hypothesis: PTEN is protected from miRNA binding by PTENP1.

    So you’re an all-powerful, all-knowing designer of genomes, and you have this gene, PTEN, whose activity you want to enhance. How do you do it?

    You have lots of options.

    You could just redesign PTEN to make it work better. Do you do that? Nope.

    You could increase the production of PTEN, have more of it around. Do you do that? Nope.

    You could duplicate the PTEN gene, and have more PTEN produced. Do you do that? Nope.

    You could down-regulate the production of the miRNA, which is a small piece of RNA that binds to the PTEN mRNA and prevents it from being transcribed into a functional protein, which you in your wisdom had previously put there so make the functional level of PTEN go down. (But apparently you went too far, since now you want PTEN activity to go back up) Do you do that? Nope.

    Instead, you duplicate the PTEN gene, but then you change it, making one copy useless, so it produces a broken protein that doesn’t do anything, and have its otherwise useless mRNA floating around to be a decoy for the miRNA.

    OK. Maybe for some subtle reason which only you in your infinite wisdom can figure out, there’s a reason for this double-decoy inhibit-the-inhibitor take-three-steps-to-do-what-could-have-been-done-in-just-one strategy, and just have to have it work by decoy inhibition of the miRNA.

    So how do you do that?

    You could just invent a new special inhibitor for the miRNA in question, tailor made to efficiently bind it. Do you do that? Nope.

    You could duplicate the original miRNA and invert it with its complementary partner, making an exact complementary opposite of the miRNA that will bind and interfere with it. Do you do that? Nope.

    Instead, you copy a gene that is over TEN TIMES LONGER than the miRNA you want to inhibit, just so you can use that tiny fraction of its sequence that binds the miRNA, and instead of just leaving it be (where it would work anyways), you change it to make it produce a useless, broken protein.

    You end up producing an additional mRNA that is a magnitude bigger than it has to be (using up all that energy needed to transcribe, translate, replicate, and eventually digest and dispose of it), just so that one tiny fragment of it can act as a decoy for another piece of RNA (the miRNA), which you could have just down-regulated directly instead but for some reason chose not to, leaving the rest of the mRNA floating around useless, where it can get accidentally grabbed by a ribosome and translated into a useless, functionless protein, wasting all the energy needed to make it, and wasting even more energy later when that useless protein has to be broken down again so that it doesn’t completely gum up the works, all the while taking up valuable ribosome time and space from the ACTUAL PTEN mRNA that you do want to translate, thereby slowing down production of it, and reducing its activity (when you actually wanted to INCREASE it’s activity).

    OK. Maybe you’ve added in another step, wherein the PTENP1 mRNA gets identified somehow so it doesn’t get transcribed, avoiding that last problem with the gumming up of the works, which human scientists just haven’t identified yet.

    So that’s now, what, at least FIVE steps (duplicate, mutate, transcribe to mRNA, decoy miRNA, prevent pseudogene mRNA from being turned into useless resource wasting protein), to do what could have been done in just TWO? Or ONE? (You know, if you had used your omnipotence to figure out what level of PTEN activity you’ll need from the start and just make it so that exactly that amount of PTEN protein is produced in the first place?)

    Why did you do that?

    WHY ON MIGHTY MAKER, WHY???

    Yep. Look at that stupendous complexity. Ludicrous complexity. Insane complexity. The kind of complexity that intelligent designers do their utmost to AVOID AT ALL COSTS, since, as any competent engineer knows, the hallmark of good design is SIMPLICITY.

    This is the kind of redundant complexity that is NOT designed, but is instead evolved.

  71. Amphiox says

    And speaking of miRNAs (http://en.wikipedia.org/wiki/MicroRNA);

    MicroRNAs originate predominantly by the random formation of hairpins in “non-coding” sections of DNA (i.e. introns or intergene regions), but also by the duplication and modification of existing microRNAs.

    They are an example of a functional element produced from mutations in previously non-coding, non-functional DNA. An example of the later repurposing of junk DNA (which is still junk up to the moment it becomes miRNA).

    It’s also an example of gain of function via duplication mutations.

    The rate of evolution (i.e. nucleotide substitution) in recently-originated microRNAs is comparable to that elsewhere in the non-coding DNA, implying evolution by neutral drift; however, older microRNAs have a much lower rate of change (often less than one substitution per hundred million years),[87] suggesting that once a microRNA gains a function it undergoes extreme purifying selection.[88] At this point, a microRNA is rarely lost from an animal’s genome,[87] although microRNAs which are more recently derived (and thus presumably non-functional) are frequently lost.[88] This makes them a valuable phylogenetic marker, and they are being looked upon as a possible solution to such outstanding phylogenetic problems as the relationships of arthropods.[89]

    miRNAs ALSO provide excellent examples of genetic drift, as well as stabilizing and purifying selection. AND their specific sequence homologies provide extremely strong evidence supporting common descent.

    I’m not sure if the texpip could have found a BETTER citation that, in one fell swoop, utterly destroys every single one of its hamster wheel repertoire of repeating lies, if it tried.

    Kudos!

  72. Amphiox says

    A little bit more on miRNA:

    http://en.wikipedia.org/wiki/File:MiRNA-biogenesis.jpg

    Notice how there is more than one way of producing miRNAs. One is from the gene transcript itself, but another is out of introns or pseudogenes.

    But notice how, from a design perspective, the first method is the ONLY one that is actually needed. NOTHING, absolutely nothing, stops an intelligent designer from producing miRNAs exclusively from the host gene transcript. After all the host gene transcripts are already there. Why create a second, entirely redundant, mechanism to produce them out of “junk” DNA? You don’t even need to have the junk DNA at all for this, you already have the coding DNA for the first method.

    WHY, OH MIGHTY MAKER, WHY???

    Unless of course, miRNAs EVOLVED, and some of them arose out of junk DNA because the junk DNA was already there and available for random mutations to act on them to turn them into miRNAs.

    And even before that, why would any intelligent designer use miRNAs as a mechanism at all? Take a look at how they work:

    http://www.youtube.com/watch?v=_-9pROnSD-A

    MORE THAN HALF of the original transcript is thrown away and never used at all. All that hairpin twisting and conformational jiggling, cutting, digesting, and splicing, NONE of it is actually necessary at all! You could get the exact same function just by transcribing the tiny functional bit like a regular gene.

    So why this needlessly complicated, over-complex, wasteful method of producing them?

    WHY OH MIGHTY MAKER, WHY???

    Unless, of course, it started from random, mutant RNA transcripts that spontaneously formed hairpin structures (which, as anyone who actually knows anything about RNA knows, is relatively easy for random mutations in RNA to produce), and evolved function in a step-wise fashion beginning from that starting point.

    And notice how it actually works, by binding to an mRNA and blocking the ribosome’s translation of mechanism from finishing translating the whole protein. Notice how kludgy and wasteful it is. The ribosome already commits to transcribing a significant chunk of the target protein before being blocked (that’s at least an ATP per amino acid in the chain, and the half-finished, useless protein has to be digested back into amino acids, wasting even more energy afterwards. Why not simply regulate at an earlier point, by blocking the ribosome from binding to the mRNA at all, or, you know, NOT TRANSCRIBING THE mRNA at all. These mechanisms are already used for the regulation of various other genes in the cell, so why doesn’t the designer reuse the more efficient mechanism?

    WHY OH MIGHTY MAKER WHY????

    Unless of course, it all started with randomly produced hairpin constructs that randomly produced miRNA segments that randomly bound, at least in part, to any free floating single stranded RNA (which again, as anyone who knows anything at all about RNA knows, is not that difficult to produce in random RNA strands), of which mRNA is one, resulting by chance in blocking the transcription of a protein and reducing its expression, which was then later selected for in an environment where it was beneficial for that particular protein to be expressed at a lower level. (Note that another major source of free single stranded RNA for miRNAs to bind to and screw up is virus RNA, so miRNAs can produce immediate benefit by protected against virus infections. It can also slow down the spread of parasitic “jumping gene” DNA in the same fashion).

    Once more this is astoundingly, amazingly, mind-bogglingly, complex, but also ludicrously, ridiculously, over-complex. It is exactly the kind of needless, wasteful complexity that intelligent designers, possessed of foresight, actively strive to ELIMINATE from their designs. It is the kind of complexity that one would not expect to be designed.

    But it is EXACTLY the kind of complexity that an unguided mechanism without foresight, dependent on pre-existing contingency, would be expected to produce as a matter of course. It is EXACTLY the kind of complexity that is expected to evolve.

  73. txpiper says

    ”Once more this is astoundingly, amazingly, mind-bogglingly, complex, but also ludicrously, ridiculously, over-complex. It is exactly the kind of needless, wasteful complexity that intelligent designers, possessed of foresight, actively strive to ELIMINATE from their designs. It is the kind of complexity that one would not expect to be designed.

    But it is EXACTLY the kind of complexity that an unguided mechanism without foresight, dependent on pre-existing contingency, would be expected to produce as a matter of course. It is EXACTLY the kind of complexity that is expected to evolve.”

    You can compare complicated systems to any number of things where efficiency and economy are not the sole objective; the Taj Mahal, for instance, as opposed to anything you (or natural selection) might personally conceive of (or select for).

    Biologically, you could observe the urinary bladder; genes and cell specialization for an extra organ requiring neural and vascular support, muscles, valves, plumbing, etc. It’s a complex, but unnecessary system, as a simple gravity drain from the kidneys would have sufficed. It is just another courteous design feature.

  74. Amphiox says

    Biologically, you could observe the urinary bladder; genes and cell specialization for an extra organ requiring neural and vascular support, muscles, valves, plumbing, etc. It’s a complex, but unnecessary system, as a simple gravity drain from the kidneys would have sufficed.

    Not in an environment filled with predators that can track you by your urine trail.

    It is just another courteous design feature.

    A solid waste uric acid system would have been MUCH more courteous. And one even exists in nature.

    So why didn’t the omnipotent omnibenevolent designer give it to the mammals?

    WHY OH MIGHTY MAKER, WHY????

    As a relic of historical contingency, of course, it makes absolute perfect sense, and is exactly what evolutionary theory predicts.

    But, as usual, for explanatory power, the texpip’s “alternative” is useless.

    *POOF*

    You can compare complicated systems to any number of things where efficiency and economy are not the sole objective; the Taj Mahal, for instance, as opposed to anything you (or natural selection) might personally conceive of (or select for).

    It is amusing to think that the texpip deludes itself into thinking my example was ONLY about “efficiency” and “economy”. The exact same observation of unnecessary complexity in evolved things applies to aesthetics as well.

    Also, it seems the texpip, pitiful idiot that it is, is under the impression that the Taj Mahal is a self-replicating entity (eggs or live birth?), because only in that circumstance would this analogy be even worth bringing up.

    The only other explanation, of course, is that the texpip is essaying another deliberately dishonest argument by false and incomplete analogy.

    Pathetic.

  75. Amphiox says

    It’s hilarious as well how the texpip, utterly incapable of responding to any of my points concerning miRNA, too lazy to apparently even try to read the links, too cowardly to admit that its arguments are all worthless, and too dishonest admit that it has yet again been caught bringing up a subject that actually thoroughly crushes its entire position, tries, desperately and pitifully, to evade the point and distract with another spin of the Gish Hamster-Wheel to another topic.

    http://www.youtube.com/watch?v=1VuMdLm0ccU

    Utterly pathetic.

  76. says

    As I said above:
    “The fight over junk seems to matter to ID proponents, but to me it seems about as trivial as arguing for the instances of “good design” nature. It makes sense if you’re trying to make the evidence compatible with an omnipotent designer, as it’s a way of explaining away that which seems at odds with what a master craftsman would build; but it doesn’t advance the notion of an intelligent designer as the question of whether or not a designer intervened is still indistinguishable from the null hypothesis.”

  77. Amphiox says

    And since the coward texpip has, it seems, once again fled the old thread in which it was getting creamed, in an attempt to avoid having to answer to the arguments presented to it there, which it simply cannot, I shall bring up once more the citations that the dishonest liar continues to evade, and continues to desperately try not to have to answer.

    http://www.nature.com/nature/journal/v489/n7417/full/nature11514.html

    http://nar.oxfordjournals.org/content/28/14/2794.full

    http://blogs.discovermagazine.com/loom/2012/09/19/the-birth-of-the-new-the-rewiring-of-the-old/#comments

    The pathetic, dishonest liar seems to think that by jumping threads we would somehow forget its past lies and past evasions.

    But we will not forget.

    And the reality of evolution remains no matter how often the texpip tries to lie.

  78. Amphiox says

    The fight over junk seems to matter to ID proponents, but to me it seems about as trivial as arguing for the instances of “good design” nature.

    Indeed, for evolutionary theory it is trivial. Evolutionary theory predicts the existence of both non-functional and functional non-coding DNA. Figuring out the relative proportions of one to the other is just a matter of filling in the details of reality.

    It is only to ID and creationists that junk DNA is an existential problem.

    Because their useless model can’t explain it at all.

  79. Amphiox says

    Biologically, you could observe the urinary bladder; genes and cell specialization for an extra organ requiring neural and vascular support, muscles, valves, plumbing, etc.

    At least one of those tubes, in just a smidge under half the human population, longer than it needs to be and has a needlessly complex and completely useless additional loop, that not only has no function but increases the likelihood of the entire system malfunctioning.

    It could have been fixed by a simple redesign that a child playing with a yo-yo could have figured out.

    And yet the designer did not do it.

    WHY OH MIGHTY MAKER, WHY????

    Of course, when viewed in the light of a blind mechanism without foresight, that produces change in a stepwise fashion mediated by random mutations and natural selection, that unnecessarily complex feature is instantly and obviously explained as an artifact of historical contingency.

    The texpip’s useless “alternative” can do nothing but shrug and call it a “mystery”.

  80. chigau (違わない) says

    Ing #86
    I really meant “here”, this thread or website or blog.
    (’cause the universe is vast, really mind-bogglingly huge)
    so
    Why here?
    Why us?
    I haven’t actively participated in this discussion but still,
    Why here?
    Why us?

  81. Amphiox says

    Every single one of the billions of people who died a slow and tortuous death by thirst and dehydration can thank the texpip’s “courteous” designer for saddling humans with the inefficient, water wasting urea-based excretion system instead of the supremely water conserving and far more convenient uric acid system it saw fit to give to the birds and reptiles.

  82. txpiper says

    “txpiper

    Why are you here?”

    Disobedience to the establishment norm, but also to give people the opportunity to read the frenzied musings of E大腸菌に手を出す人. Very convincing reading, don’t you think?

  83. Amphiox says

    Disobedience to the establishment norm

    Bwahahahaha. Says the young earth creationist.

    Even when it snarks, it lies.

    It’s like it can’t do anything else at all.

    but also to give people the opportunity to read the frenzied musings of E大腸菌に手を出す人.

    Poor, poor texpip. That’s the current topic of the OTHER thread it is infesting. Where it is getting utterly creamed, as usual. It’s getting so disoriented by the intellectual smackdown that it is receiving that its poor, small, ineffective brain, pitifully miswired by decades of self-reinforcing lies, can’t figure out where it’s supposed to be anymore.

    Maybe PZ should have some mercy and help it out by confining it to the Thunderdome, so it won’t get lost again.

  84. Amphiox says

    The texpip’s attempt to make a joke about enterohemorrhagic E. coli O157, a serious and sometimes deadly disease, as well as the overt racism, is noted.

    As previously observed, when the texpip talks about science and evolution, it reveals itself to be a clueless, dishonest, pitiful, idiotic fool.

    When it attempts to talk about anything else, it demonstrates itself to be an immoral, unethical, despicable, odious, inhuman, piece of shit.

    Utterly pathetic.

  85. Amphiox says

    Of course, since the texpip saw it fit to bring up E. coli O157 (apparently confusing it with Lenski’s different E. coli), we can note that this strain is currently undergoing the incipient stages of a speciation event.

    http://www.biomedcentral.com/1471-2164/8/121

    And it is evolving under the influence of natural selection:

    http://www.ncbi.nlm.nih.gov/pubmed/9673266

    Oh look, we’ve identified the ancestral strain from which it evolved, within the last 20 years

    http://jb.asm.org/content/187/5/1783.short

    And identified some of the mutational changes that produced the new strain, mediating its GAIN OF VIRULENCE FUNCTION.

    And more evidence of recent evolution, with the acquisition of new novel genes, in E. coli O157

    http://iai.asm.org/content/68/3/1400.short

    Once again, while the pathetic texpip faps, science marches on, and even more evidence in support of evolutionary theory is accumulated.

  86. Nerd of Redhead, Dances OM Trolls says

    It is just another courteous design feature.

    Not until you show conclusive physical evidence for your imaginary creator. You know, the evidence you never, ever show….Almost like the evidence, like your phanstasm creator, doesn’t exist….Thanks for tacitly acknowledging science is write, and you are a delusional fool believing in things that don’t exist.

  87. hotshoe says

    Every single one of the billions of people who died a slow and tortuous death by thirst and dehydration can thank the texpip’s “courteous” designer

    As parents of what we call our million-dollar baby, we have something to say to any supposed god who would torture a two-year-old boy with kidney failure from E coli 0157. What we say is if that god existed, it would be the solemn duty of every decent human to fight it to death and beyond. Why torture an innocent toddler? Yeah, punish its evil atheist parents, maybe, but how could a supposedly omnibenevolent deity punish the parents by torturing their uncomprehending little children ? That’s objectively heinous, that’s Columbian druglord kind of heinous. That’s Tonton Macoute kind of heinous. Thirtyone days in the PICU, and not quite a million dollars worth of healthcare later …
    Thanks solely to the efforts of hardworking and scientifically-educated medical professionals, our child lived. Scarred, of course, but as well as can be expected.
    No thanks whatsoever to a Mighty Maker who designed and brought into existence such a creation as E coli 0157 to begin with.

  88. txpiper says

    Hotshoe, I am sorry to hear that you and your wife had to deal with something like that. I hope your son fully recovers and remains healthy.

  89. Nerd of Redhead, Dances OM Trolls says

    I hope your son fully recovers and remains healthy.

    Missionary tactic 5, try to gain rapport with those you are preaching to. True to form.

  90. says

    Indeed, for evolutionary theory it is trivial. Evolutionary theory predicts the existence of both non-functional and functional non-coding DNA. Figuring out the relative proportions of one to the other is just a matter of filling in the details of reality.

    The only way I can make sense of it is putting it into the same kind of argument space as the problem of evil. That is, taking the intelligent designer as a particular hypothesis about the way things ought to be, then trying to reconcile any problems that come out of this view.

    For the problem of evil, we take the all-good, all-powerful God and wonder why it is that there’s so much suffering in the world; the straightforward conclusion is that such a being couldn’t have created the world. Theodicies in this sense are the ways of trying to patch up what seems contradictory to the hypothesis.

    For the design hypothesis, we take the all-powerful, all-knowing God and wonder why there are aspects of the biological organism that seem superfluous or nonsensical. Trying to promote perfect function in this sense are the ways of trying to patch up what seems contradictory to the hypothesis.

    The interesting aspect about both of these arguments is that while there’s the fight for internal consistency between the concept of God and the facts in question, the internal consistency doesn’t say anything for how reasonable either position is. After all, when an earthquake causes devastation, we don’t think that such an action is the will of a malevolent deity any more than a good deity; deities just don’t come into it at all. We understand that it’s the movement of plate tectonics that our continents sit on and has no intentionality behind it whatsoever.

    In other words, arguing over the problem of evil and the various theodicies is irrelevant to our understanding of the problem.

    And so it is with creationism. Even if one manages to find some reason for every little minutia of the biological organism, where things as they are are either for the direct benefit of the organism in question, or follow necessarily from other function that is necessarily beneficial, we still don’t have anything beyond mere consistency between the design hypothesis and life. We still don’t know how it is a designer would work, let alone be able to test for it, and how that fits into all that is known about the history of life. It’s not so much that it’s right or wrong, but irrelevant. The general hypothesis will never get a designer as it is too vague to fit into a scientific understanding of life. Proponents strive for consistency because they don’t even have that, but it would take turning the designer into a testable hypothesis that fits with our understanding of life before it’s in any way useful.

  91. intelligentdesigner says

    #65 Kel said

    doesn’t it follow to ask what would be meant by function in that sense?”

    As an analogy, consider that software, at the assembly level, has code that pushes and pops registers of the stack. One could define software functionality in such a way that it would exclude that code from the definition even though it is vital to the program. Asking ENCODE scientists to provide a narrow definition for function is a red herring. ENCODE has chosen a very broad definition of function that allows them to include what they don’t yet understand, namely, “biochemical activity”.

  92. intelligentdesigner says

    #111 Kel said

    For the design hypothesis, we take the all-powerful, all-knowing God and wonder why there are aspects of the biological organism that seem superfluous or nonsensical.

    I think the conclusion you should draw is that God is not all-powerful and all-knowing. Or that we were designed by something else that doesn’t fit your definition of God.

  93. hotshoe says

    After all, when an earthquake causes devastation, we don’t think that such an action is the will of a malevolent deity any more than a good deity; deities just don’t come into it at all. We understand that it’s the movement of plate tectonics that our continents sit on and has no intentionality behind it whatsoever.

    Well, all except for genocide-loving theologian Willaim Lane Craig. Who wrote an pious article about how we should all be grateful to god for it causing the massive earthquakes which in turn caused the lethal tsunamis. He may be lying about what he believes in order to keep the money flowing from the suckers, but he really did say that human deaths and suffering caused by plate tectonics are all part of the good plans of a good god.
    Reason #1 to hate every christian alive today: because they don’t get together to suffocate that putrid goatfucker WLC.
    Unfortunately, there are all too many assholes who believe as he says.

  94. says

    I think the conclusion you should draw is that God is not all-powerful and all-knowing. Or that we were designed by something else that doesn’t fit your definition of God.

    The point I was trying to make with #111 was that the line of inquiry is itself a red herring. It doesn’t matter because the conjecture is nonscientific, and at best only gets internal consistency. That is to say, our reason for rejecting such a hypothesis isn’t that there’s an internal contradiction, but that it goes against how we know the processes to work.

    To give an analogy, imagine someone coming up with a way to fit all the animals in the world onto Noah’s Ark; that they solve the problem of how to deal with freshwater fish, and that they can give an account of the current biogeographic distribution of life. Yet that doesn’t give us any reason to take the proposition of an ark full of all the world’s animal species seriously.

  95. Amphiox says

    Hotshoe, I am sorry to hear that you and your wife had to deal with something like that. I hope your son fully recovers and remains healthy.

    The sincerity of the above would be much more believable if the speaker did not have a track record of deliberate dishonesty, and was not the one crass enough to bring up E. coli O157 as a joke in the first place.

  96. intelligentdesigner says

    #111 Kel said,

    Even if one manages to find some reason for every little minutia of the biological organism, where things as they are are either for the direct benefit of the organism in question, or follow necessarily from other function that is necessarily beneficial, we still don’t have anything beyond mere consistency between the design hypothesis and life.

    Yes we do. We also have inconsistency with the idea that random mutation plays positive role in evolution.

  97. Amphiox says

    Even if one manages to find some reason for every little minutia of the biological organism, where things as they are are either for the direct benefit of the organism in question, or follow necessarily from other function that is necessarily beneficial, we still don’t have anything beyond mere consistency between the design hypothesis and life.

    There is more to the non-coding DNA that just the binary issue of its functionality, yes or no. There is also the mechanistic details of what functionality it has, its pattern of distribution, and its various sequences.

    And these details are fully consistent with evolutionary theory. More than that, evolutionary theory actively and successfully explains WHY these details are the way they are, as opposed to some other hypothetically possible way.

    And to make these details consistent with a design hypothesis requires postulating all sorts of bizarre, non-sensical and mutually contradictory attributes that need to be ascribed to the hypothetical designer above and beyond the mere capability for designing things.

    This turns designer “theory” into an incoherent and useless mess incapable of performing the single most important and basic requirement for a scientific explanatory theory – the generation of testable hypotheses that can be used to advance the state of human knowledge.

  98. says

    Asking ENCODE scientists to provide a narrow definition for function is a red herring. ENCODE has chosen a very broad definition of function that allows them to include what they don’t yet understand, namely, “biochemical activity”.

    But from the point of view of what junk DNA is, that it does “something” doesn’t mean it does anything that’s vital for the survival and propagation of the organism. The ALU sequences of DNA may mean that certain genes can shift their place on the genome, but that doesn’t mean that the ALU sequences are for that task.

  99. intelligentdesigner says

    Kel,

    Consider this quote from Three reasons why junk DNA makes evolutionary sense

    1. The understanding that evolution is an inherently messy and inefficient process that often produces junk. This junk may be retained if it’s not causing trouble.

    2. The realization that the vast differences in genome sizes are much better explained by junk DNA than by assuming that most DNA is truly functional.

    3. The understanding that mutational loads would be prohibitive had most of our DNA not been junk.

    Do you are with these statements?

  100. says

    Yes we do.

    Go on…

    We also have inconsistency with the idea that random mutation plays positive role in evolution.

    Go on…

  101. says

    Kel, I meant to say “Do you agree with these statements?”

    Statement 1 depends on what is meant by messy and inefficient, but I don’t really take issue with it. Statement 2 hinges on the words “truly functional” – I’m guessing they might have a more restrictive definition than what you’re proposing of the ENCODE project to use. Statement 3 seems fine prima facie, but I’m not well versed enough on the mathematics of mutation to be able to comment either way.

  102. says

    Don’t encourage the lying

    I’m happy to hear him out. I’d really like to know how internal consistency without any testable mechanism has explanatory value.

  103. intelligentdesigner says

    @123 Kel said:

    I can’t provide an adequate explanation in the short time that I have before I go to bed, but I will try a little. Basically it has to do with an explanation of why entropy applies to information. Let’s consider the paragraph:

    Mathematics is the language of science. To succeed in science, one must us mathematics. Thus high quality science depends on high quality mathematics.

    Note that I have purposely introduced an mistake into this paragraph. It should include the phrase “one must use mathematics”. We could apply a random mutation to this paragraph but only one mutation from thousands of choices will be an improvement. If I apply a second mutation it is very likely going to be a step toward nonsense. Also once that second mutation has been made, the number of modifications that could improve the paragraph would be only 2, and there would be millions of choices leading to nonsense. And on and on.

  104. Amphiox says

    ENCODE has chosen a very broad definition of function that allows them to include what they don’t yet understand, namely, “biochemical activity”.

    The ENCODE team has chosen a definition of function so broad that it can literally mean anything at all.

    And that which can mean anything means nothing.

  105. Amphiox says

    Just one step broader and “be able to dissolve in water” would count as a “function”.

  106. says

    Basically it has to do with an explanation of why entropy applies to information.

    I’m familiar with the basics of information theory. The question is, how does it apply to mutations in DNA? For example, hundreds of instances in the human genome have been found where gene duplication combined with frame-shift mutations have formed the basis of new information. I’m sure even in language you could find sentences that could be duplicated without it harming the text, and even have places where an error coupled with that duplication might add something different to the text.

    Of course, instead of coming up with analogies and wondering just how well those analogies apply, we could consult the scientific literature…
    http://www.lecb.ncifcrf.gov/~toms/paper/ev/ev.pdf

  107. says

    I can’t provide an adequate explanation in the short time that I have before I go to bed, but I will try a little.

    I’d much prefer you addressing the former question than the latter. The question of explanation is much more pertinent to my argument, whether or not mutation can produce new function (Sean Carroll’s The Making Of The Fittest had a number of examples of where mutation had a positive effect) is a largely empirical issue and will only make sense through careful experiment. Since neither of us are in the position to be able to do such experiments, we’re left relying on the peer review process and the capacities of the scientists working in those fields. But the issue of what makes for a good explanation, on the other hand, is largely conceptual, so it can be discussed and dissected without much need to have precise data at hand.

    Why is an internally consistent explanation lacking in mechanism anything more than wishful conjecture?

  108. Amphiox says

    Three reasons why junk DNA makes evolutionary sense

    The existence of junk DNA makes evolutionary sense.

    The non-existence of junk DNA also makes evolutionary sense.

    As I have previously said, junk DNA is a NON-ISSUE for evolutionary theory in general.

    Those who want to argue that non-functional junk DNA is somehow integral to evolutionary theory are doing a transparently dishonest bait and switch, hoping that their audience is not familiar with the actual history of “junk” DNA.

    And that history is this:

    1. Prior to the discovery of junk DNA, the evolutionary assumption was that ALL DNA WAS FUNCTIONAL, due to natural selection culling useless DNA from the genome.

    I’ll repeat this point for emphasis: THE ABSENCE OF JUNK DNA WAS CONSIDERED FULLY CONSISTENT WITH EVOLUTIONARY THEORY PRIOR TO THE DISCOVERY OF JUNK DNA.

    2. DNA that does not code for proteins and had no APPARENT function was observed to exist. Needing to attach a label to this discovery in order to communicate it with other scientists, the name “junk DNA” was attached to this observed DNA that did not code for proteins and had no APPARENT function.

    3. Being an OBSERVATION OF REALITY, scientists looked to evolutionary theory to provide an explanation for this observation. It was originally viewed as a challenge to evolutionary theory, as, at the time, it seemed as if evolutionary theory predicted that junk DNA should not exist. This was exciting. Scientists relish studying something that appears to challenge existing theory. This is where fame, fortune, and Nobel Prizes are won.

    4. Several evolutionary hypotheses were proposed. These included
    a) the “junk” DNA actually had a, as yet unknown, function
    b) the “junk” DNA truly had no function and accumulated because it was produced by neutral changes that natural selection could not remove.

    I will repeat this too for emphasis: Hypothesis a), that “junk” DNA actually has a function, is an EVOLUTIONARY HYPOTHESIS, generated out of the theory of evolution, and 100% consistent with evolutionary theory. Evolutionary theory, like all good scientific theories, is capable of generating multiple testable hypotheses when asked to explain specific observations. These hypotheses can, and often are, mutually contradictory. It is the job of scientists to then go out and TEST these hypotheses to see which is correct.

    And the “reasons why junk DNA makes evolutionary sense” are reasons produced by hypothesis b.

    This is an example of evolutionary theory WORKING as it should, as a good scientific theory is SUPPOSED TO WORK.

    5) And thus the two general hypotheses a) and b) are and continue to be tested. As a result we have discovered that some of the “junk” DNA has regulatory function, some of the “junk” DNA arose from parasitic sequences that hijack the normal replicating machinery to copy themselves over and over again, some of the “junk” DNA are the result of duplication mutations followed by disabling mutations that destroyed the original function, some of the “junk” DNA are the remnants of old viral infections, and so forth.

    And ENCODE is merely more data that may or may not support hypothesis a) over hypothesis b).

    But if we ever discover that even ALL of the “junk” DNA actually does have a function, an important, relevant function for the organism, then that is merely validation of hypothesis a), which is an EVOLUTIONARY HYPOTHESIS, produced BY THE THEORY OF EVOLUTION, and of course, as it must, COMPLETELY CONSISTENT WITH EVOLUTION BEING TRUE, and it brings us back to step 1, wherein it turns out that selection pressure is strong enough to ensure that all parts of the genome have function, and to remove any parts of the genome that mutate in a way that results in function being lost.

    Again, the question of the function of “junk” DNA is a NON-ISSUE with regards to the correctness of evolutionary theory in general. It is not an empirical test of evolutionary theory. Wherever on the spectrum reality actually falls, from ‘all of it has no function’ to ‘some of it has function and some of it doesn’t’ to ‘all of it has function’, it is no more than an OBSERVATION which evolutionary theory can, and does, explain perfectly well.

  109. Amphiox says

    We could apply a random mutation to this paragraph but only one mutation from thousands of choices will be an improvement.

    And if there were a self-replicating population of that paragraph with tens of thousands of individuals, then you will see on average tens of improved mutants in EVERY SINGLE GENERATION.

    If I apply a second mutation it is very likely going to be a step toward nonsense.

    But the chance of the second mutation NOT being a step towards nonsense is nonzero, and therefore, given sufficient time and sufficient generations of this self-replicating paragraph, it is bound to happen.

    Also once that second mutation has been made, the number of modifications that could improve the paragraph would be only 2, and there would be millions of choices leading to nonsense.

    And if the self-replicating population of paragraphs produces billions of replications (and it will, by simple exponential math), then the number of improved modifications will number in the millions.

    And if you apply SELECTION to this self-replicating population of paragraphs and drive the first modification to fixation then the likelihood of the two modifications combining to be an improvement is no longer the multiplied possibility of both modifications, but instead becomes JUST THE PROBABILITY OF MODIFICATION 2 ON ITS OWN. Because, thanks to selection, the probability of modification 1 existing in the population is driven up to 100% (that’s what fixation essentially means).

    Selection means that, no matter how long the chain of cumulative modifications, the probability of the whole coming together DOES NOT have to be the multiplied probability of each one in turn. By individually driving each modification to fixation one at a time, the probability of the whole chain appearing rises to only slightly less likely than any individual modification appearing by itself.

  110. Amphiox says

    And of course, having multiple mutations accumulate to, together, produce a new beneficial trait, is an OBSERVED FACT.

    http://www.nature.com/nature/journal/v489/n7417/full/nature11514.html

    http://blogs.discovermagazine.com/loom/2012/09/19/the-birth-of-the-new-the-rewiring-of-the-old/#comments

    There are AT LEAST THREE separate mutations that all have to combine to produce the GAIN OF FUNCTION mutation of aerobic citrate metabolism here. The first one (or more) whose function has not yet been figured out, the second one, a duplication that put a copy of the gene beside a different promoter, and the third one a series of additional duplications of the new gene with its new promoter.

    So arguments about the mathematical unlikelihood of Mutation A + Mutation B + Mutation C …. all having to appear to produce a new trait are irrelevant. Because we have observed it directly happening. The real world probability is 100%.

  111. Amphiox says

    Basically it has to do with an explanation of why entropy applies to information.

    The application of entropy to information not only allows for a process of random mutation and natural selection to produce new biological information and increase total biological information, it positive DEMANDS it.

    The math demonstrating this has already been done.

    http://nar.oxfordjournals.org/content/28/14/2794.full

  112. Ichthyic says

    intelligentdesigner

    I would have sworn this guy was dungeonized on the previous incarnation of Pharyngula?

  113. Ichthyic says

    As an analogy, consider that software, at the assembly level, has code that pushes and pops registers of the stack.

    yup. same guy.

    I HIGHLY recommend a repeat banning.

    he’s nothing but an irritating git.

  114. David Marjanović says

    The best Genomicron post on this mess.

    Junk DNA can as well serve simply as filling material to generate a “correct” telomer to centromer distance to mass ratio of the chromosomes in order to be processed by the spindle apparatus? Just one plausible scenario I just thought of.

    Uh, then why is the distance between telomer and centromer different in every chromosome, let alone between species?

    Case in point, who has the more complex hand, Acanthostega, with seven fingers, humans with five, bats with five plus wing membrane, T-Rex with two, or birds with zero?

    Birds don’t have zero fingers! (Except moa; they lost the forelimbs entirely, they had shoulder blades but no shoulder joints.) Most have 3, penguins have 2 (they’ve lost the thumb).

    [Insert quote from Linnaeus about humans as primates here]

    Non placet, quod Hominem inter ant[h]ropomorpha collocaverim, sed homo noscit se ipsum. Removeamus vocabula. Mihi perinde erit, quo nomine utamur. Sed quaero a Te et Toto orbe differentiam genericam inter hominem et Simiam, quae ex principiis Historiae naturalis. Ego certissime nullam novi. Utinam aliquis mihi unicam diceret! Si vocassem hominem simiam vel vice versa omnes in me conjecissem theologos. Debuissem forte ex lege artis.

    “It doesn’t please [you?] that I collated Homo among the Anthropomorpha [a name he later changed to Primates], but man is coming to know himself. Let’s set the words aside. It will be the same to me which name we use. But I ask you and the whole world for a genus-level difference between man and Simia [the other apes + monkeys] that [follows] from the principles of natural history. I most certainly do not know any. If only somebody told me a single one! If I had called man a monkey or the other way around, I would have brought up all theologists against me. I perhaps ought to have because of the law of the art [natural history].”

    MORE THAN HALF of the original transcript is thrown away and never used at all.

    Importantly, RNA isn’t for free. Adding one nucleotide to a growing strand costs two molecules of ATP – and you don’t get them back when you cut the RNA up again.

    A solid waste uric acid system would have been MUCH more courteous. And one even exists in nature.

    Birds, lizards incl. snakes, and tuataras use it. Their pee is a white paste. “Birdshit” is usually piss.

    Fun is, we produce uric acid, too – just not as much. WHY, O MIGHTY MAKER, WHY? Oh, sure, because it would give us gout – but why don’t the abovementioned animals get gout, then?

    Asking ENCODE scientists to provide a narrow definition for function is a red herring. ENCODE has chosen a very broad definition of function that allows them to include what they don’t yet understand, namely, “biochemical activity”.

    If you include “not so especially tightly coiled that stuff that floats by couldn’t bind to it anymore” in your definition of “function”, like Birney did, you’re just being silly. Comment 132 is not an exaggeration, I’m serious.

    More than half of your genome consists of rotting retrovirus corpses in all stages of decay. That’s an observed fact.

    3. The understanding that mutational loads would be prohibitive had most of our DNA not been junk.

    I don’t even understand where that comes from. The mutation rate isn’t somehow constant per genome. There’s a reason it’s expressed in mutations “per site”, per nucleotide. If you have more nucleotides, more nucleotides will mutate; as long as your number of “functional” (whatever you mean by that, as long as you’re consistent) nucleotides is constant, the number of mutations in it will also be constant, no matter how much “nonfunctional” DNA it’s hidden in.

    And why don’t bacteria that practically lack junk DNA die out among mutational chaos?

    But the chance of the second mutation NOT being a step towards nonsense is nonzero, and therefore, given sufficient time and sufficient generations of this self-replicating paragraph, it is bound to happen.

    Almost every week, somebody wins the lottery.

  115. intelligentdesigner says

    Kel and Amphiox,

    Unfortunately I am too busy to continue this conversation at this time. I’ll come back to it later but not anytime soon. If you want to continue this discussion when I am available subscribe to this post.

    Amphiox,

    I just did a quick read of http://nar.oxfordjournals.org/content/28/14/2794.full

    The simulation is seriously flawed for more than one reason. The easist to recognize is this:

    Because half of the population always survives each selection round in the evolutionary simulation presented here, the population cannot die out and there is no lethal level of incompetence.

    I plan to read this the other references you sited before returning to this conversation.

  116. intelligentdesigner says

    #142 David Marjanović said:

    Almost every week, somebody wins the lottery.

    Yeah, but how often does someone win the lottery twice in a row.

  117. says

    Unfortunately I am too busy to continue this conversation at this time. I’ll come back to it later but not anytime soon. If you want to continue this discussion when I am available subscribe to this post.

    If you’re going to respond, please stick to the question about what makes for a good explanation, and not go on about Shannon Entropy vs Natural Selection. There’s just no way that we can make any headway on that subject through analogy – it requires mathematical modelling in line with observed data, and that’s something we cannot do on the internet. What makes a good explanation, on the other hand, is something that can be thought through, and is a much more pressing concern when it comes to how it is people look at the world. It’s what I tried to highlight in #111, making a tu quoque argument against natural selection is a red herring to that point.

    Honestly, if you actually have good evidence that natural selection is incompatible with Shannon entropy, then you shouldn’t be stuck arguing in the comments section of Pharyngula. Get those findings to Nature, or to Science, or to Evolution, or to Cell. Heck, even pester Dembski and Behe with it.

  118. Nerd of Redhead, Dances OM Trolls says

    Yeah, but how often does someone win the lottery twice in a row.

    Which has nothing to do with the argument. Keep up.

    Honestly, if you actually have good evidence that natural selection is incompatible with Shannon entropy, then you shouldn’t be stuck arguing in the comments section of Pharyngula. Get those findings to Nature, or to Science, or to Evolution, or to Cell. Heck, even pester Dembski and Behe with it.

    Submission information for Science and Nature. No paper, no scientific argument, just OPINION.

    The simulation is seriously flawed for more than one reason. The easist to recognize is this:

    That which is asserted without evidence can be dismissed without evidence, Christopher Hitchens. Your OPINION can be *POOF* dismissed as fuckwittery.

  119. Nerd of Redhead, Dances OM Trolls says

    The easiest way to convince scientists that your imaginary designer exists is to provide conclusive physical evidence for it. Physical evidence that would pass muster with scientists, magicians, and professional debunkers as being of divine, and not natural (scientifically explained), origin. Tell us where to find it so it can be examined. Until then, all you have is your delusions.

  120. David Marjanović says

    Yeah, but how often does someone win the lottery twice in a row.

    Every couple million attempts?

    Because that would fit…

    Because half of the population always survives each selection round in the evolutionary simulation presented here, the population cannot die out and there is no lethal level of incompetence.

    The population cannot die out, but any particular genotype can die out – unless maybe if the population size is allowed to grow to infinity.

  121. Amphiox says

    Interesting how intelligentdesigner perseverates on a minor and essentially irrelevant detail and tries to call it a “fatal flaw”.

    And notice how its “win the lottery twice”* quip betrays that it has completely ignored my prior comment about natural selection and fixation.

    If you allow for selection to drive the lottery winner to fixation, then winning the lottery a second time is no more unlikely than winning the lottery once, as the entire population carries the “won lottery once” trait.

    *and a simple google search of “winners of lottery, twice” reveals MULTIPLE examples

  122. Nerd of Redhead, Dances OM Trolls says

    The old “winning the lottery twice” reminds me of an old computer game. The hero had to get a pile of cash from gambling. Since the odds always favor the house, it was almost impossible to get enough money in one sitting (a favorite pretense of creobots/IDiots, everything must happen at once). But, if one won a hand, and saved the game, the starting point had now changed, with less money needing to be won. The game was reloaded from the save if one lost the money. Eventually, after a few saved games, the hero had the money needed for later play.

    Just like evolution. Change a little, speciate, change further, and those lines that are success keep repeating the formula until something “final” is there, with those who lost going away.

  123. Amphiox says

    Note that the dishonest lottery analogy is the exact opposite of reality. Winners of one lottery are less likely to play again, while natural selection means that organisms possessing one advantageous mutation are more likely to have offspring inheriting that mutation with a chance of getting a second.

  124. chigau (違わない) says

    Sometimes groups of people win the lottery on the same ticket.
    And they all quit their jobs.
    And the business goes under…
    This analogy is not working.