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Rumors of pseudogenes' demise greatly exaggerated, new study says

Posted 4 August 2006 by Andrea Bottaro

I imagine that reading scientific journals is mostly a drag for ID advocates: all those papers highlighting evolutionary mechanisms, identifying transitional fossils, veryfing phylogenetic-based predictions must be really irritating. There are, however, few and far between papers that set the ID advocates' hearts all aflutter, so when one appears, they make sure to milk it for all its P.R. worth. One of the recent examples was a 2003 paper by Hirotsune and colleagues in Nature, which reported that alteration of the pattern of expression of a purported mouse pseudogene (i.e. an apparently inactivated, non-functional gene, part of the so-called "junk DNA") results unexpectedly in the modification of the activity of its functional counterpart, leading to a series of dramatic developmental defects. Now, one of the recurrent claims of Intelligent Design is that most if not all of the features of any organism, including its entire genome, should somehow be useful. Thus, ID advocates enthusiastically latched on Hirotsune's publication as supporting their claim that "junk DNA" is, in fact, not junk at all (indeed, if you Google for "Hirotsune" and "Intelligent design", you will find over 100 hits). Alas for them, a brand new paper by Todd Gray and colleagues in the Proceedings of the National Academy of Sciences appears to completely refute the original findings. As usual, let me give the background first. Pseudogenes can be defined as the remnants of once-coding DNA sequences that have undergone a more or less significant loss of their ability to encode for any product. There are two main sources of pseudogene formation (see figure 1). The first is traditional gene duplication, followed by the loss of functionality by one of the duplicated members. The second is by a mechanism called retrotransposition - in short, the messenger RNA of a gene, instead of being used for protein synthesis, is transcribed back into a DNA sequence and inserted into the genome, forming so-called "retrogenes". Unlike pseudogenes arising from gene duplication, which often retain the original regulatory elements required for gene expression (promoters/enhancers), retrogenes lack regulatory sequences, and therefore their only chance of becoming expressed is when they integrate in proximity of some other gene's promoter (rather unlikely, although not impossible) [3,4]. If they don't become expressed and aquire some selectable function, they quickly degenerate, turning into retrotransposed or "processed" pseudogenes. A third, more rare instance is that of functional genes losing their function in certain lineages, but not others ("unitary" pseudogenes - a classic example is the independent inactivation of the gene for vitamin C synthesis in primates and guinea pigs). retrogenes-jpg.JPG Figure 1: Origins of pseudogenes: A. Retrotransposed pseudogenes: starting from the original gene (the coding sequences are in black, the non-coding introns in gray, and the promoter element is indicated by the large arrow upstream of the gene), transcription generates a primary mRNA (black and gray broken line), from which the introns are excised by RNA splicing. This mature mRNA, which contains only exons and a poly-adenosine tail, is transcribed back into DNA by enzymes called reverse transcriptases, and the DNA is reinserted back into the genome. Hence, the pseudogene product will lack intron and promoter sequences, and will bear characteristic repeat sequences at the insertion site, due to the integration mechanism. B. Duplicated pseudogenes: DNA duplication generates a more-or-less faithful copy of the original gene, including introns and, in many cases, promoter and other transcriptional regulatory elements. In most cases, this duplicated gene will undergo crippling, inactivating mutations and turn into a pseudogene (in rarer cases, the duplicated copy will acquire new functions and become a new gene). (Adapted from [3].) Thus, pseudogenes - and especially retrotransposed pseudogenes - are generally considered to be non-functional relics and, together with other sorts of repetitive and "selfish" DNA elements, as well as other unique DNA sequences, form the so-called "junk DNA". (For a more general discussion of "junk DNA", see Ian Musgrave's discussion here at PT.) Indeed, when the pseudogenes can be followed over evolutionary lineages, they appear to evolve neutrally, accumulating mutations progressively and freely until they become almost unrecognizable, or disappear from the genome altogether. Note that the number of pseudogenes in the human genome (20,000 or so at the latest count, many of them crippled viral elements) is comparable to that of our functional genes - an impressive amount. Despite its connotations, the phrase "junk DNA" (originated by Susumu Ohno in 1972) does not intend to convey an absolute and irreversible lack of function. Indeed, as it is often noted, had that been the case "garbage DNA" would have been a better term. In fact, "junk" is what accumulates in people's basements and attics, not immediately useful but not nasty or burdensome enough to be quickly discarded -- indeed, something that may occasionally be found to be of use (at least, that's what I tell my wife). Another problem with the term is that it is unfortunately often misused (in the lay press and especially by Creationists, although some scientists are guilty as well) to simply denote DNA that does not directly encode any protein sequence - which is absolutely wrong. It has long been known, in some cases even before the term was coined, that DNA contains important non-coding elements involved in gene transcription (e.g. the promoter and enhancer elements mentioned above), RNA splicing and polyadenylation, chromosome dynamics, etc. In addition, instances exist where the sequence of a particular stretch of DNA is irrelevant, but its presence may be important, as in the case of introns, certain "spacer' regions, and so on. Still, while it is clear that the term "junk DNA" should be used advisedly (if at all) there are good reasons to think that large swaths of the genome of most eukaryotic organisms are indeed non-functional, in part because these stretches of DNA accumulate mutations neutrally, and diverge much faster than known functional elements, and also because vast differences in DNA amount, presence of large duplications/deletions of intergenic regions, as well as gain and loss of specific pseudogenes are often observed in closely related organisms (see again Ian's piece). Ironically, the term "junk DNA" was originally often used as pretty much a swipe by supporters of the "neutral theory" (which argues that much of what goes on in the genome is actually non-adaptive and not subject to selective forces) against the more strictly neo-Darwinian "pan-adaptationists", for whom the long hand of natural selection reaches every nook and cranny of an organism's phenotype and genotype, continually getting rid of even mildly noxious or just useless features, like some obsessive-compulsive cleaner. With time, however, the accumulating evidence for selective neutrality of large parts of the genome convinced even the more strict Darwinians, and only Creationists and ID supporters have remained to argue the ultra-Darwinian pan-adaptationist position (although of course from different premises). ID advocates in particular have often discussed junk DNA as an important issue for their "theory". For instance, in his quasi-peer-reviewed paper in the Proceedings of the Biological Society of Washington, Stephen Meyer claimed that

Advocates of the design hypotheses on the other hand, would have predicted that non-coding regions of the genome might well reveal hidden functions, not only because design theorists do not think that new genetic information arises by a trial and error process of mutation and selection, but also because designed systems are often functionally polyvalent. (Meyer SC, Proc Biol Soc Wash 117:213-239. 2004)

Jonathan Wells wrote

From an ID perspective, however, it is extremely unlikely that an organism would expend its resources on preserving and transmitting so much "junk". (Wells J, PCID, Vol 3.1, 2004) [Note here the similarity to the ultra-Darwinian argument: carrying "junk DNA" looks like a waste of resources, hence maladaptive for the pan-adaptationist, or "bad engineering" for the ID advocate. AB]

which prompted the Discovery Institute's Casey Luskin to boldly venture (while lawyerly hedging his bets) that ID predicts that

Much so-called "junk DNA" will turn out to perform valuable functions.

ID connoisseurs would perceptively note here that these strong statements about "junk DNA"'s function seem to contrast with the shyness of ID advocates regarding the attributes, goal and identity of the Designer (why couldn't She be a compulsive junk collector, as far as Her critters' genomes go, after all?). But ID advocates have of course at least two good reasons to support this view: first, the admission of a careless or incompetent Designer would constitute a bad P.R. move with the movement's religious supporters, and second, if uniquely identifiable junk DNA elements, like pseudogenes, are indeed non-functional, then their observed transmission along evolutionary lines (see for instance this paper) is powerful evidence of common descent, with which most ID advocates have yet to make peace. Given this context, Hirotsune's paper in 2003 must have seemed like a dream come true. The paper's findings were actually serendipitous, but totally striking: while generating a transgenic mouse strain (i.e. a strain of mice in which an artificial gene has been added to the genome, in order to study its effects), Hirotsune realized that one of their strains presented an unusual phenotype in which various developmental defects in the kidneys and bones presented themselves at very high frequency, but only when the transgene was inherited from the father (genes that are expressed differentially when they are inherited maternally or paternally are called "imprinted"). Looking at the genomic region in which the transgene was inserted, the authors found a processed pseudogene (Makorin-1p1, or Mkrn1-p1 in genetic notation) with similarity to an expressed, functional gene called Mkrn1. By further characterizing the phenomenon at the molecular level, the authors claimed that the Mkrn1-p1 pseudogene showed transcription into RNA only when inherited paternally (i.e., it was itself imprinted), that this expression was diminished by insertion of the transgene in its proximity, that the Mkrn1-p1 RNA product could regulate expression of the Mkrn1 functional gene by affecting stability of its mRNA, and that the phenotype due to Mkrn1-p1 suppression could be rescued by enforcing expression of either Mkrn1 or Mkrn1-p1 RNA. In short, they claimed to have demonstrated that RNA from a processed pseudogene can play a regulatory role in the expression of its ancestral, protein-coding gene counterpart. Now, this is without doubt a very interesting finding, although of limited general applicability (as I mentioned, the majority of retrogenes do not give rise to any RNA), and of course ID advocates jumped on it with a vengeance. In the wake of the Hirotsune paper, Mike Behe even submitted a letter to Nature, which declined publishing it. Among other things, the letter stated:

The modern molecular example of poor design is pseudogenes. Why litter a genome with useless, broken copies of functional genes? It looks just like the aftermath of a blind, wasteful process. No designer would have done it that way.(2) Yet Hirotsune et al (3) show that at least one pseudogene has a function. If at least some pseudogenes have unsuspected functions, however, might not other biological features that strike us as odd also have functions we have not yet discovered? Might even the backwards wiring of the vertebrate eye serve some useful purpose?

Cautionary Note: if you wish to read the entire text, please make sure to shut off your irony meters first: in the letter, Behe sternly warns the scientific community against the perils of purely negative argumentation, and chastises them for naively trusting their "intuition" regarding biological function - rather cheeky, for someone whose main arguments against evolutionary theory are that we don't have a complete mutation-by-mutation model of the evolution of certain biological structures, and that

The strong appearance of design allows a disarmingly simple argument: if it looks, walks and quacks like a duck, then, absent compelling evidence to the contrary, we have warrant to conclude it's a duck. (Michael Behe, "Design for Living", The New York Times, 2/7/2005)

Anyway, back to the main story. Although ID advocates are keen to claim that the "darwinian orthodoxy" routinely suppresses or ignores inconvenient results, Hirotsune's paper caused quite a splash, and rapidly accumulated over 100 citations in the scientific literature, most endorsing the new model of "pseudogene trans-regulation" (trans here is lingo for "acting on another chromosome") proposed by the authors [e.g. 4,5]. Other scientists pursued the lead trying to investigate the conservation of the putative regulatory portion of Mkrn1-p1, albeit with mixed results [6, 7]. Still, there were some reasons for skepticism -- for instance, the Mkrn1-p1 retrogene, despite its purported crucial role in mice, is absent from the genome of all other mammals tested, including closely related rats. In addition, the Makorin gene family counts at least 3 functional members in the mouse (including, of interest, a bona fide functional retrogene, which is transcribed, conserved in mammals, and encodes the Makorin-3 protein), as well as numerous pseudogenes, which can complicate molecular and sequence analysis. Finally, previous studies on mice with chromosomal alterations including the segment near the Mkrn1-p1 gene suggested that no imprinted gene with deleterious effects was present in the region. Enter Gray and colleagues, which in their PNAS paper systematically re-analyzed the original story and tested some of its predictions. Their findings consistently contradicted the Nature paper's conclusions: they found that the Mkrn1-p1 pseudogene is not transcribed at all, and that the RNA attributed to the pseudogene by Hirotsune is actually a variant form of transcripts from the functional gene; that the pseudogene's DNA is extensively modified by methylation, a known hallmark of transcriptional inactivity; that neither Mkrn1 nor Mkrn1-p1 are imprinted; and finally that inactivation of the functional Mkrn1 gene does not bring about the changes observed in Hirotsune's transgenic mice. Gray therefore concludes that Hirotsune's data were mostly artifactual, and (quite generously) propose some alternative mechanisms of how those findings came to be originated. Where does this leave us with regard to pseudogenes? Actually, pretty much where we were before the Gray paper came out. If you take away the hype and ignore the wishful thinking of ID supporters, the evidence still overwhelmingly supports the notion that many, likely most pseudogenes are functionless, and it does so regardless of the validity of Hirotsune's findings. Indeed, if one assumes that evolutionary conservation of DNA sequences is a strong hallmark of potential function, then a recent study by a Swedish group shows that at best a few dozens of the thousands of pseudogenes in the human and mouse genomes are under sufficient selective pressure to be highly conserved between the two lineages, suggesting they may be functional [8]. Still, there is ample room for potential interesting mechanisms by which pseudogenes can on occasion be recruited into regulatory and structural functions. There is, of course, also an important lesson about science here: Hirotsune's provocative, out-of-the-mainstream findings were not rejected on principle, but were given wide exposure, embraced by some as explanatory of certain processes, put to the test by others, and invalidated. Of course, this will apply to Gray's data as well -- it is now up to Hirotsune and his supporters to test the new findings and explain them away, or accept them. Stay tuned. Acknowledgements Thanks to Ian, Nick, Douglas, Reed, Dunk Erik and the rest of the PT crew for useful comments and suggestions. REFERENCES 1. Hirotsune S, Yoshida N, Chen A, Garrett L, Sugiyama F, Takahashi S, Yagami K, Wynshaw-Boris A, Yoshiki A. An expressed pseudogene regulates the messenger-RNA stability of its homologous coding gene. Nature. 2003 423:91-6. 2. Gray TA, Wilson A, Fortin PJ, Nicholls RD. The putatively functional Mkrn1-p1 pseudogene is neither expressed nor imprinted, nor does it regulate its source gene in trans. Proc Natl Acad Sci USA. 2006 Aug 1; [Epub ahead of print] 3. D'Errico I, Gadaleta G, Saccone C. Pseudogenes in metazoa: origin and features. Brief Funct Genomic Proteomic. 2004 3:157-67. 4. Balakirev ES, Ayala FJ. Pseudogenes: are they "junk" or functional DNA? Annu Rev Genet. 2003;37:123-51. 5. Zhang Z, Gerstein M. Large-scale analysis of pseudogenes in the human genome. Curr Opin Genet Dev. 2004 14:328-35. 6. Podlaha O, Zhang J. Nonneutral evolution of the transcribed pseudogene Makorin1-p1 in mice. Mol Biol Evol. 2004 21:2202-9. 7. Kaneko S, Aki I, Tsuda K, Mekada K, Moriwaki K, Takahata N, Satta Y. Origin and evolution of processed pseudogenes that stabilize functional Makorin1 mRNAs in mice, primates and other mammals. Genetics. 2006 172:2421-9. 8. Svensson O, Arvestad L, Lagergren J. Genome-wide survey for biologically functional pseudogenes. PLoS Comput Biol. 2006 2:e46.

42 Comments

Glen Davidson · 4 August 2006

Actually, the modern molecular example of "poor design" is taking a gene or pseudogene which encoded one function and causing it to code quite a different function. Like we find with flagellum genes.

IDists are trying to claim function as necessarily being the result of design (though they might allow for evolution of some simple changes). That's why they jump all over themselves when apparent "junk" turns out to have some function, despite the fact that the real challenge for an honest "design theorist" is to explain why so many genes appear to have evolved from other genes.

It's the old vestigial organs dodge. If you bring up a "useless organ" they'll do their best to give it a function, as if that would explain the teeth in young platypuses and in young baleen whales, or why the cold gives us gooseflesh. Sure, teeth never used for their apparent primary function might be of value in development of gums or some such thing, and gooseflesh might have some trivial functions as well. But function does not explain form, "design" gives us even less of an explanation than does function, so that no explanatory value has been gained whether or not pseudogenes or platypus teeth have function.

Well and good if their precious example of a pseudogene that appeared to have function blows up on them, but they have no explanation whatsoever for either the functional pseudogenes that do exist (apparently with regulatory effects) or for the non-functional pseudogenes that also almost certainly exist (there are far too many with unknown functions to believe that all regulate gene activity or perform some other task, plus we know that a number of pseudogenes have been co-opted for other uses without undue dire consequences--hence these latter must not have had crucial functions, at least).

Does it even occur to Behe to ask why a pseudogene is what regulates expression, if indeed it does? What functional purpose is served by adapting a gene to act as a regulatory agent? It is one of the mechanisms open to RM + NS (plus the rest, yes), but it does not seem to be a particulary intelligent design, and certainly not the sort of thing that would define design against a backdrop of mutation and selection.

Behe has to begin with an assumption of design to react as he does, trying to fend off the many evidences against design as an explanation. Apparently the matter of actually explaining why things are as they are based upon design requirements, goals and aims of the designer, or rational efficient design, simply doesn't interest him. He explains things according to chemistry, so that the biological arrangements not required by chemical constraints seem arbitrary to him, thus arbitrary whim by some feckless "designer" comports with his limited scientific view.

And our desire for explanations and useful knowledge pale in comparison with his desire to produce religious apologetics. Too bad for those who wish to understand, that isn't part of the agenda of certain sectors of American Xianity.

Glen D
http://tinyurl.com/b8ykm

JohnK · 4 August 2006

ID response:
"How did prestigious Nature come to publish Hirotsune's mistaken paper? Yet more evidence that the science establishment is flawed, its feet are clay, the game is rigged, the ship has sailed, and much so-called "junk DNA" will in fact turn out to perform valuable functions because no one has yet shown all of it has none, and just look at that shiny object over there."

normdoering · 4 August 2006

Andrea Bottaro wrote:

I imagine that reading scientific journals is mostly a drag for ID advocates: all those papers highlighting evolutionary mechanisms, identifying transitional fossils, veryfing phylogenetic-based predictions must be really irritating.

And let's not forget scientists who actually evolve complex genetic trait in the laboratory: http://biosingularity.wordpress.com/2006/02/04/scientists-evolve-a-complex-genetic-trait-in-the-laboratory/

Unsympathetic reader · 4 August 2006

There is no a priori reason to assume that a designer would not produce organisms with the ability to accumulate 'junk' DNA. One could argue that the ability to incorporate adaptive changes in the genome is an example of 'good' design and that 'junk' DNA is just a byproduct of that capability.

As noted, unless a particular mode of design or the intent of a designer is postulated, nothing can contradict 'design' as an explanation. Similarly, 'design' predicts nothing and gives no hint of what to expect.

Henry J · 4 August 2006

I'd suppose that sometimes the effects that produce "junk" dna act faster than the selection effects that reduce it (presumably because it saves resources). When that happends, the "junk" expands. At some point we get a balance between the opposing effects.

I wonder if recombination increases the tendency to create duplications in the dna? (Relative that is to asexual reproduction.)

Henry

Tulse · 4 August 2006

There is no a priori reason to assume that a designer would not produce organisms with the ability to accumulate 'junk' DNA.

— Unsympathetic reader
That's certainly true if one is making absolutely no assumptions about the Designer. That said, when Behe explicitly argues:

No designer would have done it that way.

that looks to me like one of the few solid claims that can be tested empirically -- if no functionality can be found for junk DNA, the Behe would have to admit that as a strike against ID.

steve s · 4 August 2006

Junk DNA is just the biological incarnation of Sturgeon's Law: 90% of everything is crap. ;-)

Peter Nyikos' imposter · 4 August 2006

I don't know why would IDists make a huge deal regarding the Hirotsune paper. Even if we assume the results are valid, it would be an exception to the rule that most pseudogenes are functionless relics.The PNAS paper is an excellent example of how science is tentative, as science usually corrects the mistakes of other scientists.

Anonymous_Coward · 4 August 2006

There is no a priori reason to assume that a designer would not produce organisms with the ability to accumulate 'junk' DNA. One could argue that the ability to incorporate adaptive changes in the genome is an example of 'good' design and that 'junk' DNA is just a byproduct of that capability.

Yes, that does show how ID can be conjured to explain anything. But wasn't there an argument that junk DNA is a major point against irreducible complexity rendering ID, specifically IC, as bogus? Or am I really behind the times and Creationists have already changed their tune?

Does it even occur to Behe...

I'm not even sure that it has occurred to anyone sympathetic to their point of view that this whole ID thing is just a well disguised descendant of the centuries old Argument by Design logical fallacy.

IDists are trying to claim function as necessarily being the result of design (though they might allow for evolution of some simple changes). That's why they jump all over themselves when apparent "junk" turns out to have some function, despite the fact that the real challenge for an honest "design theorist" is to explain why so many genes appear to have evolved from other genes.

I think the bigger challenge (STILL) is why ID "theory" doesn't predict the use of certain junk DNA. Instead, they wait for a genuine research discovery and (in the words of someone else) "spoonfeed" to those who are gullible and ignorant enough to believe it. Waiting for real scientists to make discoveries and say "we knew that" is like when Pat Robertson said he "predicted" the hurricanes that hit Florida or whatever. Or how I made the remarkable and proven prediction that the sun will rise tomorrow.

Michael Suttkus, II · 4 August 2006

They have been predicting it. They were claiming there was no Junk DNA back when I started debating creationists in 1999, four years before the 2003 Hirotsune paper.

And that's Sturgeon's Revelation. Sturgeon's Law is something else, at least according to Sturgeon:

http://en.wikipedia.org/wiki/Sturgeon%27s_law

Andrea Bottaro · 4 August 2006

No designer would have done it that way.

that looks to me like one of the few solid claims that can be tested empirically --- if no functionality can be found for junk DNA, the Behe would have to admit that as a strike against ID.I think Behe may have been paraphrasing Ken Miller in that sentence (see the reference he provides). In reality, as noted by others, ID does not pin itself to any definitive prediction with regard to "junk DNA". For the base, they will play the "efficient engineering" angle as long as it is viable, but be assured that should things turn the other way, they'll just revert back to the "we can't presume to understand the Designer" line (see for instance this rather disconnected post by Denyse O'Leary at UD). As for empirical tests, it's essentially technologically impossible to delete all the "junk DNA" from an organism to prove it is junk. However, experiments doing it piecemeal show that one can delete large chunks of DNA from mice with no detectable ill effects, and comparison of genomes of closely related species show significant rates of insertions/deletions, some very long, in intergenic regions. And of course, there are closely related organisms with very different DNA amounts, such as the frogs Xenopus tropicalis and Xenopus laevis, the latter of which carries around twice the genome (its ancestors underwent a whole genome duplication) and very large numbers of duplicated pseudogenes.

steve s · 4 August 2006

Comment #116875 Posted by Michael Suttkus, II on August 4, 2006 01:27 PM (e) | kill They have been predicting it. They were claiming there was no Junk DNA back when I started debating creationists in 1999, four years before the 2003 Hirotsune paper. And that's Sturgeon's Revelation. Sturgeon's Law is something else, at least according to Sturgeon: http://en.wikipedia.org/wiki/Sturgeon%27s_law

According to that wikipedia article, I see that Sturgeon was wrong about the names of his statements, and common usage has corrected him ;-)

normdoering · 4 August 2006

Unsympathetic reader wrote:

There is no a priori reason to assume that a designer would not produce organisms with the ability to accumulate 'junk' DNA.

Riiighhht, the designer could have also designed things so that they would evolve over a couple billion years, from simple single celled forms on up to us. This is called theistic evolution and it's not an alternative scientific theory -- it's an alternative philosophical interpretation of a theory, the other alternative being metaphysical naturalism.

Erik 12345 · 4 August 2006

In addition, instances exist where the sequence of a particular stretch of DNA is irrelevant, but its presence may be important, as in the case of introns, certain "spacer' regions, and so on.

— Andrea Bottaro
Do you have any examples of how the presence (and length?) of a stretch of DNA can be important, while the nucleotide sequence is irrelevant? I partly ask because I don't know for sure myself and partly because I think it would add to the presentation of your arguments.

386sx · 4 August 2006

IDists are trying to claim function as necessarily being the result of design (though they might allow for evolution of some simple changes). That's why they jump all over themselves when apparent "junk" turns out to have some function, despite the fact that the real challenge for an honest "design theorist" is to explain why so many genes appear to have evolved from other genes.

— Glen Davidson
Right. But, as far as those creationists are concerned, what it really boils down to is this: Would the "Designer" create "junk" DNA or would the "Designer" not create "junk" DNA? And that is a theological debate "designed" to appear as though it's really a scientific debate.

That's certainly true if one is making absolutely no assumptions about the Designer. That said, when Behe explicitly argues:

No designer would have done it that way.

— Tulse
that looks to me like one of the few solid claims that can be tested empirically --- if no functionality can be found for junk DNA, the Behe would have to admit that as a strike against ID.

Wrong. There is nothing that is a strike against creationism. Even if there were, good luck getting a creationist to admit it. Oh look! A strike against ID. "Poof!" Oops! No it's not.

Dave Carlson · 4 August 2006

This looks to me like a perfect research opportunity that the Discovery Institute did not taking advantage of. If the DI is really as interested in scientific research as they claim, why didn't they use Hirotsune's Nature as a starting point for doing their own research into the possible utility of "junk dna?" They certainly like to talk about the stuff. If this is really all about the science, why don't they do some actual research on junk dna?

(I know that's pretty much a rhetorical question, but it's an important one, nonetheless.)

Anonymous_Coward · 4 August 2006

They have been predicting it. They were claiming there was no Junk DNA back when I started debating creationists in 1999, four years before the 2003 Hirotsune paper.

Well, that kind of highlights my point. They predicted there was no junk DNA, but they still do not try and use ID to predict that specific use with their "theories" of IC and SC and such. That's why saying that there might be uses for DNA that hasn't been "studied" is like "predicting" that the American Midwest will be struck with at least one tornado this year. Except the latter has actual proof while the former is more like a hopeful wait.

genotypical · 4 August 2006

Henry J. -- You are right, gene duplication can be associated with recombination. Typical tandem duplications, such as the one that Andrea shows in Part B of the diagram, are generally believed to originate from unequal crossing over during meiosis, i.e. the two homologous chromosomes are not perfectly aligned during a recombination event, so one loses and one gains a small piece of DNA that may contain a gene. If the duplicate-gene version becomes common in a population, then in homozygotes the first copy on one chromosome can mispair at meiosis with the second copy on the other chromosome, increasing the chances of additional duplications. This leads to clusters of related genes and pseudogenes, which are fairly common in large genomes; a well-known example would be the hemoglobin gene clusters in mammals.

Michael Suttkus, II · 4 August 2006

Yes, ID doesn't necessarily make any predictions of what a designer might do. However, we all know the phrase "Unnamed Intelligent Designer" is a lie.

The Unnamed Intelligent Designer is God.

Behe can say it might be aliens all he wants, but we all know what the DI is really pushing. The Judeo-Christian God, completely with great big capital G.

The reason that ID can't predict what an intelligent designer might do is because nothing (other than intelligent) is really postulated. Wihtout a specific designer, you can't make effective predictions. Insert a specific designer and suddenly predictions become possible.

Did my grandmother design all life on Earth? No! My grandmother lacks the technological skills, the biochemical understanding, and wasn't alive 4.5 billion years ago. A specific designer let's us make some specific predictions.

What can we say about the Unnamed Intelligent Designer Who Is Secretly God? Well, God is all good, so he couldn't lie by making a universe that just looks like it's really old and life evolved if it weren't true. God is all powerful and omniscient, so there's no room for mistakes. Neither can damage be attributed to malice.

Does DNA look like it was designed by such a designer? Nope. It looks like it was slapped together by a moron. It looks like it evolved.

Michael Suttkus, II · 4 August 2006

And, if ID can't be warped to include God as a tennible option, ID ceases to be an issue in any real sense.

Pointing out pseudogenes doesn't call ID into question, but it cuts the heart out of why the DI is wasting time blithering about it.

Popper's ghost · 6 August 2006

Insert a specific designer and suddenly predictions become possible.

Inserting God, or "the Judeo-Christian God" doesn't make predictions possible, because there's no consistent model of behavior that determines its actions.

What can we say about the Unnamed Intelligent Designer Who Is Secretly God? Well, God is all good, so he couldn't lie by making a universe that just looks like it's really old and life evolved if it weren't true.

Of course he could. First, not all lying is bad. Second, it's deception, not lying, but perhaps it's a test of faith -- a good test, in God's view. Third, the Judaic God is not "all good" by our criteria, nor claims to be. Or, to put it another way, if a petty vengeful destructive God who plays favors for certain tribes is "good", then anything can be "good".

God is all powerful and omniscient, so there's no room for mistakes.

All we can say is that whatever such a God did, he intended. There's no room for us claiming that certain outcomes are mistakes.

Neither can damage be attributed to malice.

The OT God is full of malice. In any case, damage attributable to God is Godly damage. If everything Godly is good, then any such damage is good damage. You're trying to put the cart before the horse to obtain falsifiable claims about God's behavior, but the God thesis isn't falsifiable (which is another way of saying it's meaningless mumbo jumbo, but that's another matter).

Does DNA look like it was designed by such a designer? Nope.

"such a designer" is not a definite description, so the question has no answer.

It looks like it was slapped together by a moron. It looks like it evolved.

Those two claims are not compatible. In fact, the latter is true and the former is false; it doesn't look like it was slapped together by anyone.

Popper's ghost · 6 August 2006

They predicted there was no junk DNA, but they still do not try and use ID to predict that specific use with their "theories" of IC and SC and such.

The critical distinction is between people predicting things and a theory predicting things; the former isn't relevant to science. Of course, it's a distinction that the IDists try to obscure because ID makes no predictions -- it entails no causal consequences. It doesn't even entail any existentials, like "there is junk DNA" or "there isn't junk DNA", or "there are IC systems" or "there aren't IC systems". ID consists of two claims:
  • There are systems too complex to have evolved.
    • But it seems that at most we could say that a system is too complex to have evolved in the given time with the current theory of evolution, calling for revisions in the theory or the time estimates. However, as we know, the evidence doesn't support the claim and the math offered by the IDists is bogus.
  • Either a system evolved or it was designed.
    • But this produces an infinite regress, since it entails that the designer either evolved or was designed. The only way out seems to be a designer that designed itself, but that appears to be a logical impossibility, and the burden is surely on anyone who claims otherwise to explain how that is possible. And positing an undesigned designer contradicts the claim; If there can be one exception, why can't there be others? An alternative might be something like "Either a system evolved or was designed or resulted accidentally or randomly or sprang into being out of nothing or has always existed or some other alternative we haven't thought of". In any case, the ID claim entails a contradiction and must be rejected, along with ID.

    normdoering · 6 August 2006

    Either a system evolved or it was designed. But this produces an infinite regress, since it entails that the designer either evolved or was designed.

    Actually, I think they have a very different metaphysics where intelligence/spirit (whatever that is) is the primal, eternal stuff of the universe.

    Popper's ghost · 6 August 2006

    Actually, I think they have a very different metaphysics where intelligence/spirit (whatever that is) is the primal, eternal stuff of the universe.

    I didn't touch on intelligence, just design. The "intelligent" in ID is usually construed as distinguishing it from the "merely apparent" design of agent-free processes like evolution. Your comment really isn't relevant (I also don't think it's true of IDists, although it is true of pantheists and possibly some theistic evolutionists).

    normdoering · 6 August 2006

    Popper's ghost wrote:

    Either a system evolved or it was designed. But this produces an infinite regress, since it entails that the designer either evolved or was designed.

    Actually, I think they have a very different metaphysics where intelligence/spirit (whatever that is) is the primal, eternal stuff of the universe. I didn't touch on intelligence, just design. Can you have design without intelligence? Either a system evolves or it is designed -- by an intelligence.

    Your comment really isn't relevant

    That depends on how you define your terms.

    (I also don't think it's true of IDists, although it is true of pantheists and possibly some theistic evolutionists).

    It's true of most Christians. Remember Genesis, an eternal, omnipotent God sort of wills things into existance with holy words or some such.

    Popper's ghost · 7 August 2006

    Your comment really isn't relevant

    That depends on how you define your terms. No, it depends on your not paying any attention to the argument against ID that I actually wrote and being argumentative for no good reason. The "not evolved; therefore designed" false dichotomy has been noted by many people, as has the infinite regress; I merely summarized it. Metaphysical views on intelligence as a fundamental essence of the universe aren't relevant because the ID argument asserts that this intelligence manifested in specific circumstances, designing and creating an organism or biological system instead of letting it evolve as part of the natural (and perhaps essentially intelligent) unfolding of the universe.

    Frank J · 7 August 2006

    I imagine that reading scientific journals is mostly a drag for ID advocates: all those papers highlighting evolutionary mechanisms, identifying transitional fossils, veryfing phylogenetic-based predictions must be really irritating.

    — Andrea Bottaro
    C'mon now. Where else can they get all that evidence to cherry-pick and all those juicy quotes to mine?

    Michael Suttkus, II · 7 August 2006

    The critical distinction is between people predicting things and a theory predicting things; the former isn't relevant to science.

    — Popper's ghost
    Good point, you're quite correct about that. Same with your comments on my deriving predictions from the Specific Designer. I was trying to be as nice to the IDiots as possible, giving them a false science instead of abjectly stupid anti-science.

    Andrea Bottaro · 7 August 2006

    Erik12345 wrote: Andrea Bottaro wrote: In addition, instances exist where the sequence of a particular stretch of DNA is irrelevant, but its presence may be important, as in the case of introns, certain "spacer' regions, and so on.

    Do you have any examples of how the presence (and length?) of a stretch of DNA can be important, while the nucleotide sequence is irrelevant? I partly ask because I don't know for sure myself and partly because I think it would add to the presentation of your arguments.Sorry for not answering this earlier - busy week-end, kids back from camp. I was referring mainly to three issues there . The first is the recurrently made claim that the presence of introns within eukaryotic genes may have some adaptive value. Without going into a lot of detail about this (unless someone is specifically interested), you can read the discussion Arlin Stoltzfus and myself had a couple years ago in the comment thread to this PT post. The second issue has to do with gene regulation. It has become more and more evident, as genomic sequence accumulated, that genes are clustered in limited subregions of the genome, and that genes within the same subregions often share regulatory properties - e.g. are expressed in the same tissue, or in response to similar stimuli, etc. It is thought, and in some cases we have good evidence for it, that these chromatin "domains" are under control of long-range transcriptional regulatory elements, which can sometimes act on many genes over hundreds of thousands of kilobases. The problem then arises, how genes in one domain can be isolated from the effects of long-range control elements in neighboring domains. In some cases, specialized elements (i.e. "insulators") capable of directionally limiting the action of a regulatory sequence have been shown to do this. In other cases, however, it seems that distance itself - e.g. megabase pairs of nonsense DNA, often organized in tightly wound heterochromatin - may buffer expression domains safely enough. The third possibility that is sometimes mentioned (although I am not sure I entirely buy it) is that presence of extra DNA may somewhat buffer against DNA damage due to certain forms of toxic agents, such as oxygen radicals, or against intragenic DNA breakage and recombination (which is potentiallty more disruptive than extragenic breakage). None of these is sufficient to really explain the abundance of non-genic "junk" DNA we find in most eukaryotic genomes, but they may explain some, and it's something to keep in mind when discussing the issue.

    Torbjörn Larsson · 7 August 2006

    Popper's:

    "But it seems that at most we could say that a system is too complex to have evolved in the given time"

    You made a really good comment. Specifically on this, my favourite reason why "too complex to have evolved" is bunk is made by Mark Chu-Carroll by looking at Chaitin's complexity theory: "The fundamental result is: given a system S, you cannot in general show that there is no smaller/simpler system that performs the same task as S." ( http://scienceblogs.com/goodmath/2006/06/the_problem_with_irreducibly_c_1.php )

    That means that irreducible complexity isn't welldefined, because it would mean solving the halting problem or conversely disproving gödel incompleteness. "There is absolutely no way that you can show that any system is minimal - the idea of doing it is intrinsically contradictory."

    As I understand it the idea of IC is embedded in and debunked by the idea of simplicity. This is what happens when Behe's subtractive IC (take away a part and the system fails) is debunked by scaffolding and exaptation. It wasn't IC at all, and the problem is what we can't look at a system and say that it is IC or too complex to have evolved.

    Torbjörn Larsson · 7 August 2006

    "As I understand it the idea of IC is embedded in and debunked by the idea of simplicity."

    BTW, complexity debunked by simplicity is pretty ironic.

    Torbjörn Larsson · 7 August 2006

    ""As I understand it the idea of IC is embedded in and debunked by the idea of simplicity."

    BTW, complexity debunked by simplicity is pretty ironic."

    And I can't refrain from stating that one can always trust creationists to take a perfectly simple situation or concept, turn it around 180 degrees and end up with its ass in their face.

    Anonymous_Coward · 7 August 2006

    That means that irreducible complexity isn't welldefined

    To many, irreducible complexity is just a sad attempt at sounding technical while in all essence is just a rewording from previous arguments from design, arguments from incredulity etc. I don't think you can define those logical fallacies because there's just so many forms they can take.

    normdoering · 7 August 2006

    Torbjörn Larsson wrote:

    Popper's: "But it seems that at most we could say that a system is too complex to have evolved in the given time"

    You made a really good comment. Specifically on this, my favourite reason why "too complex to have evolved" is bunk According to this article (which Dembski is trying to spin on UnComDe): Technology Design or Evolution? http://www.technologyreview.com/read_article.aspx?id=17089&ch=infotech

    But evolved systems have their disadvantages. For one, they suffer from "subsystem inscrutability." That is, when we direct the evolution of a system, we may know how the evolutionary process works, but we will not necessarily understand how the resulting system works internally. For example, when the computer scientist Danny Hillis evolved a simple sort algorithm, the process produced inscrutable and mysterious code that did a good job at sorting numbers. But had he taken the time to reverse-engineer his system, the effort would not have provided much generalized insight into evolved artifacts.

    So now, according to Dembski, simplicity rather than copmplexity is the sign of design: http://www.uncommondescent.com/index.php/archives/1411

    Conversely, then, if we can figure it out (which we are doing more and more of each day), then we're looking at something that was designed.

    Popper's ghost · 7 August 2006

    A conclusion that I draw from my reading is this: if biological life developed via evolutionary algorithms, then we shouldn't be able to figure it out.

    — WAD
    Dembski should just have "I am an IDiot" tattooed on his forehead and get it over with. From the article he cites (emphasis added):

    we may know how the evolutionary process works, but we will not necessarily understand how the resulting system works internally.

    It seems that Dembski misread that as "necessarily not". Also from the article:

    For example, when the computer scientist Danny Hillis evolved a simple sort algorithm, the process produced inscrutable and mysterious code that did a good job at sorting numbers. But had he taken the time to reverse-engineer his system, the effort would not have provided much generalized insight into evolved artifacts.

    It seems that Dembski misread that as "Any effort to have reverse-engineered the system would have failed miserably because it's impossible to understand evolved systems no matter how much time and effort is put into it". IDiot, idiot, IDIOT, it's all the same.

    Torbjörn Larsson · 7 August 2006

    "So now, according to Dembski, simplicity rather than copmplexity is the sign of design"

    Yes, ID may have a slow creepage of ideas from the obviously useless (since it contradicts other useful theories by design :-) towards useful. In Dembski's case it is pretty obvious since he always use variation on his definitions, so selection is natural for him. :-)

    Unfortunately in this case it doesn't help since also the simplicity that complexity was imbedded in isn't well defined.

    Theron Corse · 7 August 2006

    What can we say about the Unnamed Intelligent Designer Who Is Secretly God? Well, God is all good, so he couldn't lie by making a universe that just looks like it's really old and life evolved if it weren't true. God is all powerful and omniscient, so there's no room for mistakes. Neither can damage be attributed to malice.

    — Michael Sutkkus
    How would we distinguish between a naturalistic world and one designed by an incompetent, inefficient, or malicious deity? For that matter, how could science distinguish between God, capital G, and sufficiently advanced aliens? I know, I know, these questions are undergrad dorm bull session questions, but these are the questions that ID raises. Thus I will continue to ignore them.

    fnxtr · 8 August 2006

    Where's a good place for a layman to learn more about the vitamin C pseudogene? As in how, specifically, it differs from the functional gene and what actual research has been done on h. sapiens sapiens and other primates?

    Dogpiling "Vitamin C pseudogene" and "broken vitamin C gene" didn't give any sites more detailed than 'there is such a thing', plus a claim on a creationist site that it's only been found in one human and no apes. No idea where that claim came from.

    Michael Suttkus, II · 9 August 2006

    I thought I posted this yesterday, oh well. Here are some basic discussions:

    http://www.talkorigins.org/faqs/molgen/
    http://www.talkorigins.org/faqs/comdesc/ (It's in part 4, but the whole things is a good read.)

    fnxtr · 9 August 2006

    Thanks, Michael!

    fnxtr · 9 August 2006

    Now we need gene therapy to fix the broken vitamin C gene. Shouldn't be too hard. Maybe the merchant marine union could pay for the research, heh heh... or maybe it's just cheaper to stow Flintstone chewables in the galley.

    Henry J · 11 August 2006

    Re "Now we need gene therapy to fix the broken vitamin C gene."

    Maybe some duct tape?