Tuesday, April 16, 2013

Educating an Intelligent Design Creationist: Evidence for Junk

I'm replying to a post by andyjones (More and more) Function, the evolution-free gospel of ENCODE. That was the fourth post in an exchange between me and him. In response to his latest post, I'm working my way through five issues that Intelligent Design Creationists need to understand. So far, we've covered four of them.

Educating an Intelligent Design Creationist: Introduction
Educating an Intelligent Design Creationist: Pervasive Transcription
Educating an Intelligent Design Creationist: Rare Transcripts
Educating an Intelligent Design Creationist: The Specificity of DNA Binding Proteins
Educating an Intelligent Design Creationist: The Meaning of Darwinism

Intelligent Design Creationists have difficulty understanding the arguments for junk DNA and the evidence that supports those arguments. We try to explain the genetic load argument but it doesn't seem to penetrate. We try to explain that half of our genome is composed of defective transposons and viruses—often fragments of the intact genes. This doesn't phase them. And no matter how many times we describe the "C-value Paradox" and why junk DNA resolves the paradox, that evidence is ignored. We patiently describe the megabase pair deletions of the mouse genome and why this is evidence of junk. We teach them about copy number variation in the human genome and why DNA fingerprinting works. We show them examples of deletions and insertions in the genomes of different individuals telling them that these seem to have no effect as far as we know. We take time to explain modern evolutionary theory and why it is consistent with junk DNA. Finally, we describe our detailed textbook understanding of transcription and DNA binding proteins and they don't listen.

Andyjones says,
The fact that some very good scientists have not found functions for all of the genome does not negate the many functions they have found so far, for many classes of genetic element, including those commonly classed as ‘junk’. And they are still working. Part of the problem is this: if a layperson were to take apart a microchip, would he be able to discern the function of all the parts at the first attempt? Probably not. The problem is not lack of intelligence, but an early lack of understanding of the principles by which the thing is built. As soon as he understands a particular design principle, suddenly huge areas of the chip will be comprehensible to him. I humbly suggest that we have a number of such minor revolutions ahead of us in molecular biology. We are making great strides, but we do not yet understand all the principles of the transcriptome never mind the whole interactome. Perhaps there is more to learn about binding sites for RNAP? Or take pseudogenes: they have already been found to function in some cases as regulators, through their RNA transcripts interacting with real gene RNA transcripts. Then, alternative splicing is only partly understood. Who knows what other mechanisms operate at the RNA level? If you can’t imagine the function yet, it can be pretty hard to find it. But if one asserts there is no function (for example for rare transcripts) like Larry does, it will be even harder to find it.
This is a common theme among the Intelligent Design Creationists and, in fairness, among many molecular biologists. They think that junk DNA is simply an expression of ignorance. They ignore everything we tell them. They think that just because they don't understand something then nobody else does either.

In spite of what our opponents say, we actually have a pretty good understanding of the principles behind how a genome is built. Population genetics tells us that it ain't designed.

When I assert that rare transcripts probably have no function I'm not just talking through my hat and I'm not the only biochemist who says that. When I say that one million little bits and pieces of Alu SINES are very unlikely to have a function, that's not just idle speculation. When the ENCODE workers try to tell me that most of the genome is a huge web of 636,336 regulatory sequences, I can test this claim against the vast amount of information that we already know about genomes and transcriptional regulation and declare that this makes no sense. These are not arguments from ignorance.

Opponents of junk DNA are never going to be credible unless they tell us why the genetic load argument is invalid. They need to explain how their ideas comport with the data on genome size (The Onion Test). They need to explain why the average gene needs 5000 regulatory sites. They need to come up with a reasonable explanation for lack of sequence conservation. They need to tell us why the vast majority of defective transposons evolved a function.

Opponents of junk DNA need to address the arguments and evidence for junk DNA and stop pretending that those arguments don't exist.


  1. You neglected to link to the places you discussed those arguments previously. Here's the genetic load one:


  2. The argument that we simply haven't learned yet what the function of junk DNA is falls apart when one considers the simple observation that junk DNA is not what we started with as an explanatory concept for the majority of the genome. It was forced upon us by the data and in general, the more we have learned about how biology works and genomes have evolved, the more important role non-adaptive processes seem to play. Had you asked someone in early 20th century whether whatever the carrier molecule of inheritance is consists of 90-95% non-functional sequence, he would have been baffled by the very idea.

    This, BTW, is a common reversal of the historical pattern of the development of science that creationists like to use. The argument goes that scientists have this a priori atheistic commitment, it is dogma that prevents them form seeing the light, and eventually science will come to its sense after more research is done and will embrace god. Well, that's not at all how things developed historically - scientists were religious and were forced to abandon God by the data as he became either obsolete as an explanatory device, or the factual claims of religions were found to be false. The junk DNA "debate" seems to be simply yet another manifestation of this more general phenomenon

  3. What suprises me most are researchers doing RNAseq who publish junk-derived lncRNAs as functionally important in the same paper state that these are non-translated and occur with less than one copy per cell. When I say low copy numbers I mean really low copy numbers. Down to 0.0006 copies per cell which equals one in about 1700 cells containing a certain lncRNA as stated by the Mattick lab (Mercer et al. 2011, doi:10.1038/nbt.2024). While translation may compensate for low copy numbers e.g., in embryonic stem cells which are reported to have low copy numbers in general how should a single RNA molecule in one of up to thousands of cells confer any function? How would its cognate binding site copmpete with similar sites in the genome? Are other rare transcripts taking over its function in the other cells? If networks as complex as assumed by ENCODE members really exist are these networks different in every cell as one would expect if always only a fraction of these RNAs is expressed in a single cell? Or shall we beleave that these transcripts are only expressed very shortly during cell cycle and get immediately degraded invoking the impression of low steady state levels?

    (ETA: Since I was in a hurry the phrasing of my earlier comment was not good and I messed up transcription and translation at one point. Thus I deleted the other commet. However, the message remains the same.
    ETA: again (Blogspot sometimes is a pain)

    1. It's doubtful that all proposed lncRNAs are functional, but people have knocked down a number of them and have gotten ad phenotype, so a good number certainly are. In the same time, it has to be pointed out that one usually looks for spliced lncRNAs in RNA-seq data, as the monoexonic contigs are simply uninterpretable at this point, and there is tons of the them.

  4. A "difficulty understanding the arguments for junk DNA and the evidence that supports those arguments" is not NECESSARILY something that ID/creationist HAVE. It very well may be that their understanding is incomplete or flawed, but who among us has a complete and perfectly accurate understanding of anything, much less of something as complex as the minutia of genomics. Just because someone does not wholeheartedly endorse an interpretation of evidence does not mean that they largely misunderstand it. Explanations of a theory and descriptions of textbook explanations are merely that . . . explanations and descriptions.
    "One man's null hypothesis is another man's face palm."

    1. Not necessarily something they have, but clearly is something they have. A Creationist who can articulate Ohno's argument, or the nature of transposons and the reasons why the million or so Alu fragments are not considered functional just because some appear in genes, is a rare beast. So rare, in fact, that I have never encountered one. Those who understand that junk was not a prior assumption of biology, but a discovery, are equally rare. It is easy to be convinced one knows all one needs to know in order to dismiss an aspect of science. Or so it appears. "Nobody understands everything" is true, but irrelevant.

    2. Creationists seem not to be able to "get it" that some genuine function discovered among nontranslated DNA sequences does not mean that all nontranslated sequences are non-junk. For the most visible creationists this is simply a dishonest debating tactic. But for many other creationists it is simply something they desperately want to be true. It is a design that their Designer would not make.

      If you point out some bad design, and ask whether their Designer would do that, most of the time they argue that we cannot speculate on the motives of the Designer. And therefore they argue that your objection is wrong. But when it comes to junk DNA this argument evaporates -- they really really badly want to believe that most of the genome isn't junk. It is a Good Design argument after all.

    3. @joe,

      Creationists seem not to be able to "get it" that some genuine function discovered among nontranslated DNA sequences does not mean that all nontranslated sequences are non-junk.

      In fairness, there are many of our colleagues who fall into this same trap. There are papers in the scientific literature claiming that most pseudogenes are functionl because a few have been shown to have a function. There are papers claiming that most defective transposons are not junk because a few have been co-opted to a functional role. And there are tons of papers claiming that all transcripts have a function just because a small minority have been proven to have a function.

      These scientists seem to think that the exception disproves the rule rather than the other way around. I wonder if there's a name for this fallacy?

    4. Good question. I think in our colleagues we are dealing with people who like to think of the cell as this big marvellous intricate machine. They are delighted by the thought that we are just scratching the surface, and there there will be decades of well-finded work ahead finding out how all the control machinery in the formr junk DNA works.

      They don't have a populational or evolutionary perspective. They don't understand the strength of the arguments for the reality of junk DNA, arguments that you are doing such a good job of wielding,

    5. What about the ‘nucleo-skeletal’ and ‘nucleotypic’ theories promoted by Cavalier-Smith and by Bennett and Ryan Gregory, respectively?

    6. Here is one ID creationist's attempt to answer the Onion Test. (Spoiler alert: He fails):


    7. Joe Felsenstein:
      Good question. I think in our colleagues we are dealing with people who like to think of the cell as this big marvellous intricate machine. They are delighted by the thought that we are just scratching the surface, and there there will be decades of well-finded work ahead finding out how all the control machinery in the formr junk DNA works.

      They don't have a populational or evolutionary perspective. They don't understand the strength of the arguments for the reality of junk DNA, arguments that you are doing such a good job of wielding,

      I would add that many of them suffer from disproportionate self-confidence and lack the ability for self-reflection.

  5. Part of andyjones' criticism is obvious: Just because we haven't discovered a function for junk DNA doesn't mean there isn't any such function. Moran's response addresses this concern by asserting that there is positive evidence for the nonfunctioning of junk DNA, above and beyond simply not having been able to discover any function so far. I am curious, what is the nature of this positive evidence? I'm neither a biologist nor a chemist, so probably I will not understand it anyway. But it concerns me that Moran made no attempt to outline it, as would seem natural for someone claiming that such evidence exists.

    1. One example that was referred to - delete a huge amount of DNA from the mouse and see what happens. If the mouse line is not distinguishable from wildtype, this does not support a "hidden function" hypothesis (abstract below).

      Also, we continually make transgenic mice by BAC transgenesis - random insertion of chromosomal regions containing genes-of-interest into the mouse chromosomes. Good labs use multiple clones (ie mouse lines from difference insertion events), and in most cases, the phenotype is the same, and due to the presence of the inserted gene and not due to mutating the insertion site. Since in all of these cases, you can insert into the target site a big piece of DNA with no consequence, it begins to argue against a function for the target site and surrounding region.

      In contrast, in the fruit fly (smaller, condensed genome, less junk DNA), this is complicated by positional effects, but also the high probability of disrupting neighboring gene sequences. This starts to imply that there is no immediate function for that extra DNA in the mouse.


      Nature. 2004 Oct 21;431(7011):988-93.
      Megabase deletions of gene deserts result in viable mice.
      Nóbrega MA, Zhu Y, Plajzer-Frick I, Afzal V, Rubin EM.


      The functional importance of the roughly 98% of mammalian genomes not corresponding to protein coding sequences remains largely undetermined. Here we show that some large-scale deletions of the non-coding DNA referred to as gene deserts can be well tolerated by an organism. We deleted two large non-coding intervals, 1,511 kilobases and 845 kilobases in length, from the mouse genome. Viable mice homozygous for the deletions were generated and were indistinguishable from wild-type littermates with regard to morphology, reproductive fitness, growth, longevity and a variety of parameters assaying general homeostasis. Further detailed analysis of the expression of multiple genes bracketing the deletions revealed only minor expression differences in homozygous deletion and wild-type mice. Together, the two deleted segments harbour 1,243 non-coding sequences conserved between humans and rodents (more than 100 base pairs, 70% identity). Some of the deleted sequences might encode for functions unidentified in our screen; nonetheless, these studies further support the existence of potentially 'disposable DNA' in the genomes of mammals.

    2. Ben, look at the second to last paragraph. There you will find encapsulated two of the main arguments for junk DNA. First, the "c-value paradox", also known lately as the "onion test", which is the high variation in genome size among species, including closely related ones. And second, the lack of sequence conservation between species, as one would expect if the sequence were under purifying selection.

    3. TheOtherJim (and John Harshman),

      Ah, I did miss that, so thanks for pointing it out.

      That mouse study (the one with the abstract) is exactly what I was looking for. Very interesting. The other stuff you mention is interesting too. Thanks!

  6. It is surprising that two of the best supported theories on the function of ‘junk DNA’ (jDNA), the ‘nucleo-skeletal’ hypothesis proposed by Thomas Cavalier-Smith and the ‘nucleotypic’ hypothesis proposed by Michael Bennett and promoted by Ryan Gregory are not discussed on this blog. Again, this is very surprising because Ryan is a frequent contributor to Sandwalk.

    Is there any reason to pretend that these theories, which have been described in dozens of articles and books, do not exist?

  7. I've heard it from one of the top evolutionists: I don't remember the exact words, so pls bare with me:
    "Human genome was once compered to a car for larger audience to understand the issue. It may have been done by Wojciech Makalowski
    but I'm not sure. I can't find this quote.

    Human genome can be compared to a car. Junk DNA issue is like a 6 year old boy looking at the car. Scientists investigating the human genome can be compered to a 6 year old, because their knowledge sometimes resembles that. 6 year old looks at the car and he says there are repetitive elements it the car. We don't need it. And he removes the hood, the extra seets, but he gets to wheels and a mechanic tells him you need 4 wheels to for the car to run. That is true. But, how many bolts do you need to hold that wheel tight? the 6 year old says you only need 2 out of 5. The car will be fine just with 2 bolts. The mechanic says you really need at least 4 or even 5 bolts because the designer, the engineer who tested this says it is the best for your car because in the long run, if one of those bolts became loose, your whole wheel will come off. By having 5 bolts you are safe even though critics will tell you that you are a fool by taking the extra precautions.

    Sorry, it was a long one

    1. I would recommend that you stop buying domestic cars and go with imports.

      And don't let your 6 year old service your vehicle any more.

    2. @steve oberski

      I almost exclusively drive imports that now have become domesticated; they are made in North America, and they are just as reliable as when they were made in Japan :)

      BTW: Did you get the point? Remember, both ID creationists and Larry have their backup plans for Junk DNA. If it is proven one day that human genome has a lot of junk, ID creationists are ready to accept it and they have their own explanation how that can be explained with the existence of a Designer.

      Larry, on the other hand says, that if human genome turns out to be fully functional, it will not disprove the theory of evolution.

      I'm personally between the two parties. I think almost all of human genome will turnout to be "functional"(each wheel bolt will turn out to be essential in the long run)with some junk, such as the accumulation of mutations that deleterious.

    3. I'm going to revitalize this subject because I would like to hear what if? I hope YOU-LARRY and others trying to be as good as him, mind, would you?

    4. Dominic,

      The problem would not be for the theory of evolution per se in your hypothetical scenario. After all, until 1972, no-one had any inkling that the human genome could be such a waste of space, and evolution had survived this assumption intact. If it turns out the genome is overwhelmingly functional, we are back pre-1972, but with the 1972 question requiring an answer. The work of Ohno served (slowly) to convince that the length of genome could not sustain the mutation load if sequence was essential throughout. Subsequently the nature of this apparent genetic fluff that can undergo extensive mutation without detriment has been characterised, and plausible reasons for its accumulation against expectation proferred.

      As it stands, it looks like you are backing the wrong horse. If you are right, it's no big deal - it would generate some head-scratching, but scientists aren't afraid of data.