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Tuesday, May 31, 2011

Gil Dodgen Explains the Salem Conjecture

The Salem Conjecture is the work of Bruce Salem. He suggested in the mid 1990s on that of those creationists who claim professional expertise in evolution, a substantial percentage are engineers.

Bruce explained that most engineers are NOT creationists. It's only those who think they have special insight into biology who tend to be creationists.

This conjecture seems to hold but nobody knows why. It's one of the great mysteries of the world, right up there with why so many people hang toilet paper incorrectly and why it's only men who need to change after they get married.

Finally, after 15 years, Gil Dodgen offers an explanation for why engineers have such special insight into evolution [Who are the Real Freethinkers, Darwinists or ID Folks?].
The only thing I can think of is that the average Darwinist has no experience in designing any complex, functionally integrated system. The workings of the simplest cell make my AI program and the hardware on which it runs look like tinker toys.....

Self-replication does nothing to mitigate the probabilistic hurdles the Darwinian mechanism must overcome. How could this not be obvious to anyone with any experience in software or any other rigorous engineering discipline, and who has a basic understanding of combinatorial mathematics?

Oops, I forgot, most of these people have no experience in any rigorous engineering discipline. And those who do, and still believe in the Darwinian fantasy, have obviously undergone the atrophy and crippling of their basic reasoning powers — the product of many years of Darwinian indoctrination and suppression of free thought.

Who are the real freethinkers, Darwinists or ID folks? The Darwinian world is Orwellian.

Well, I'm glad that's settled. Now, I wish he'd turn his attention to some of the other serious mysteries that call out for an engineer's special insight. Maybe he can tell us the correct way to hang toilet paper?

(BTW, the posting just went up a few hours ago and there aren't any comments yet. I expect a flood of comments criticizing Gil for being rude to the scientists Darwinists. We all know that the IDiots are very sensitive about such behavior. They pride themselves on being polite and respectful toward their evolutionary biology Darwinist opponents.)

Monday, May 30, 2011

Junk DNA Poll

If you haven't answered the junk DNA poll question in the margin then now's the time! There's only one week left.

The results so far are surprising—very different from my previous poll on this topic. It looks like one side is wining.

The Central Dogma Strawman

Whenever you're trying to promote a new idea it's nice to have a scapegoat to beat up on. You're going to get a lot more attention if you can demonstrate that your latest results overthrow some key scientific concept that everyone took for granted. If you can't find a real "key concept" then the next best thing is to make one up.

For the past several decades that strawman target has been The Central Dogma of Molecular Biology. The Central Dogma is supposed to represent the key concept of molecular biology yet it gets "overthrown" on a regular basis every six months. Isn't that strange?

The latest example comes from a Nature review of a recent Science paper. The Science paper presents evidence that many mRNA sequences differ from the sequences in the exons that encode them (Li et al., 2011). RNA editing has been known for decades and every few years it is trotted out again as proof that the Central Dogma is wrong. The recent Li et al. (2011) paper doesn't present evidence for a new phenomenon but it does suggest that RNA editing may be much more common than previously suspected.

Here's what Nature staff writer Erika Check Hayden says about this paper ("Cells may stray from 'central dogma'" Hayden, 2011a).
All science students learn the 'central dogma' of molecular biology: that the sequence of bases encoded in DNA determines the sequence of amino acids that makes up the corresponding proteins. But now researchers suggest that human cells may complicate this tidy picture by making many proteins that do not match their underlying DNA sequences.
Now if that really was what the Central Dogma actually said then it would have disappeared thirty years ago.

The real Central Dogma of Molecular Biology is ...
... once (sequential) information has passed into protein it cannot get out again (F.H.C. Crick, 1958)

The central dogma of molecular biology deals with the detailed residue-by-residue transfer of sequential information. It states that such information cannot be transferred from protein to either protein or nucleic acid. (F.H.C. Crick, 1970)
I've explained why this is the correct version in an old blog posting from 2007: Basic Concepts: The Central Dogma of Molecular Biology. A very similar definition can be found on the Wikipedia site: Central Dogma of Molecular Biology. The key point is that once information flows into protein it can't flow back to nucleic acid. The standard misconception of the Central Dogma is actually the normal information flow pathway or what Crick called the "Sequence Hypothesis." It's a generality that was never meant to be an inviolate rule like the actual Central Dogma.

Hayden has another article in this week's print version of Nature (Hayden, 2011b). The second article emphasizes the controversy surrounding the Li et al. (2011) paper—lots of people are skeptical—but she doesn't back off the implications.
If verified, the findings would require a rewrite of the 'central dogma' of molecular biology, which posits that the RNA transcripts that carry genetic information to the ribosome, where they are used as templates for protein assembly, are generally faithful matches to the original DNA.
There are two remarkable things about such a statement. First, RNA editing has been an established fact for almost thirty years so if the Central Dogma needed rewriting it would have been done a long time ago. Second, Hayden was informed in the comments to her first article that there was a problem with her definition of the Central Dogma. Maybe she didn't have time to change the second version that was about to be published.

To be fair, this isn't just a problem with science writers who don't do their homework. Hayden is right when she says that most science students learn an incorrect version of the Central Dogma of Molecular Biology. It's true that most textbooks promote the information flow pathway as the Central Dogma and they fail to point out that the real version only precludes reverse translation. I don't understand why so many textbook writers and teachers continue to teach something they know to be false as the "Central Dogma" of molecular biology.

Is it because they don't know about the exceptions?

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

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

Hayden, E.C. (2011a) Cells may stray from 'central dogma.' Nature Published online 19 May 2011 [doi:10.1038/news.2011.304.

Hayden, E.C. (2011a) Evidence of altered RNA stirs debate. Nature 473:432. [doi:10.1038/473432a]

Li, M., Wang, I.X., Li, Y., Bruzel, A., Richards, A.L., Toung, J.M., and Cheung, V.G. (2011) Widespread RNA and DNA Sequence Differences in the Human Transcriptome. Science. 2011 May 19. [Epub ahead of print] [Science]

Sunday, May 29, 2011

The Black Knight

It's been fun battling the IDiots over junk DNA but it's time for a break. For no particular reason I thought of this video.

Friday, May 27, 2011

IDiots vs the Truth

I don't expect the IDiots to agree with me. I don't expect them to be happy about what I say. But I do expect them to tell the truth, or at least make the attempt.

Over at Evolution News & Views David Klinghoffer posted the following under: At Forbes, John Farrell Joins in "Ayala'ing" of Jonathan Wells.
Thus we have several posts from University of Toronto biochemist Larry Moran, criticizing Myth while being totally open about not having read it first. Moran wrote no fewer than four posts on the book in this fashion, claiming as an excuse that Myth would not be published in Canada until May 31. (In fact, the book was available for purchase from Amazon since early May.)
The four postings are:
  1. Junk & Jonathan: Part 1—Getting the History Correct—a posting in which I addressed an interview of Jonathan Wells conducted by Denise O'Leary.
  2. Junk & Jonathan: Part 2— What Did Biologists Really Say About Junk DNA?—a posting in which I addressed an interview of Jonathan Wells conducted by Denise O'Leary.
  3. Junk & Jonathan: Part 3—The Preface—a discussion of the preface that was posted online.
  4. See the IDiots Gloat over Jonathan Wells—a blog posting about what David Klinghoffer had to say about me and the book.
Only one of these postings was about the contents of the book and that one was about the preface, which I had read. In all these postings I was careful to say that I had not read the book but it was on order. I was waiting for it to arrive.

My order was placed weeks ago on Their website said that the book would not be released until May 31. Fortunately was able to ship it to me last week and I was happy to get it.

Now that I've read the book it will be interesting to see if David Klinghoffer has any comments about my review.

Thursday, May 26, 2011

Junk & Jonathan: Part 8—Chapter 5

This is part 8 of my review of The Myth of Junk DNA. For a list of other postings on this topic see the link to Genomes & Junk DNA in the "theme box" below or in the sidebar under "Themes."

Pseudogenes are the classic example of junk DNA and, as pointed out by many evolutionary biologists, they represent a difficult challenge for Intelligent Design Creationists. It's especially difficult to explain pseudogenes that are located in the same place in different species.

Chapter 5: Pseudogenes—Not so Pseudo After All

Chapter 5 is Pseudogenes—Not so Pseudo After All. This is the chapter where Jonathan Wells takes the standard creationist approach to the problem of pseudogenes—he denies that they exist!

Wells begins the chapter by reminding us that several evolutionary biologists have challenged the IDiots to come up with an explanation for pseudogenes, especially those that are found in closely related species. The usual suspects are quoted: Ken Miller, Douglas Futuyma, Jerry Coyne, Richard Dawkins, and John Avise. All of these challenges are based on solid evidence that most pseudogenes are actually pseudogenes (non-functional, degenerate copies of functional genes). But Wells says, "Yet there is growing evidence that many pseudogenes are not functionless, after all."

Types of Pseudogenes

There are three kinds of pseudogenes [Pseudogenes]. The first category contains genes that used to be functional in our ancestors but currently are non-functional. The best example is the human GULOP pseudogene that used to encode a key enzyme in the pathway for synthesis of vitamin C [Human GULOP Pseudogene]. This gene is active in most animals but it has become a pseudogene in primates and, independently, in a few other animals.

UPDATE: see: Creationists questioning pseudogenes: the GULO pseudogene

The second category includes genes that arise from a gene duplication event followed by inactivation of one of the copies. These pseudogenes tend to be located near their active siblings and they retain most of the features of the original gene except they can't produce an active product. Many of them are transcribed, especially if they have only recently become pseudogenes.

The third category is called "processed" pseudogenes. They arise when a mature mRNA molecule is copied into DNA by reverse transcriptase and the resulting DNA is integrated into the genome. Processed pseudogenes will usually not have any introns and when they integrate they will not be near a promoter. Many of them are truncated because the copying process was not complete. Processed pseudogenes were never able to produce their original functional product (protein or RNA) and they accumulate mutations at the rate expected from fixation of neutral alleles by random genetic drift.

The first two categories of pseudogene will also accumulate mutations once they become inactive. It's a characteristic of pseudogenes that the older they are the more mutations they have. Thus a pseudogene that is only found in chimpanzees and humans will have fewer mutations than one found in monkeys and apes and even fewer that one found in both rodents and primates.

The human genome contains about 20,000 pseudogenes, about the same as the number of genes. Many of these pseudogenes belong to the same family so not every gene has a corresponding pseudogene. About 6,000 of these pseudogenes arose from duplication events and 14,000 are processed. (The first category is rare.)

The pseudogenes in the "duplicated" category tend to be associated with large families of related genes. For example, in the human genome there are 414 pseudogenes in the olfactory receptor gene family [Olfactory Receptor Genes, The Evolution of Gene Families]. It's difficult to imagine how any substantial number of these genes could have a function.

As expected, the processed pseudogenes are scattered thoughout the genome because they insert at random. Roughly 2,000 of them are found in introns and this is further evidence that introns are mostly junk. Of course, if a processed pseudogene plunks down in an intron sequence it will be transcribed. Processed pseudogenes tend to come from functional genes that are abundantly expressed in the germ line. That's because the processed pseudogene has to be integrated into germ line DNA in order to be passed on to the progeny. Most of these genes are standard housekeeping genes. For example, there are 1300 pseudogenes derived from ribosomal protein genes.

Jonathan Wells describes the three categories but doesn't explain any of the other things I just mentioned.

Transcribed Pseudogenes

The first important section of his chapter is "Transcribed Pseudogenes." He quotes a number of papers showing that some pseudogenes are transcribed in humans, cows, and plants. In humans he claims that about one-fifth of pseudogenes are transcirbed at some time or another. This is probably an upper limit since most workers suggest that only 10% are transcribed.

I'm sure that some pseudogenes are transcibed. Many of the pseudogenes derived from gene duplication events will still be transcribed from active promoters even though they may not produce a functional product. Many of the processed pseudogenes will be transcribed because they are found within a gene (introns) or have fortuitously integrated near a promoter.

'Pseudogenes' That Encode Proteins

The key question is whether any pseudogenes produce a functional product and that's addressed in the next section: "'Pseudogenes' That Encode Proteins." Wells describes five studies where presumed pseudogenes were found to be genes after all (three in humans and two in fruit flies). Interesting but irrelevant. These genes are not junk. What about the other 20,000 real pseudogenes? Here's what Wells says at this point in the chapter ...
To be sure, only a relatively small proportion of known pseudogenes have been shown to encode proteins. But there is growing evidence that RNAs transcribed from pseudogenes perform essential functions in the cell
Here's where we get to the most important part of the chapter. It's in a section called "RNA Interference."

RNA Interference

RNA interference arises when one RNA molecule interferes with the expression of another. The easiest example to understand is when part of a gene is transcribed in the opposite direction producing what's called "antisense" RNA. This antisense RNA will hybridize to the functional mRNA and either block translation or induce degradation. In either case, less protein is made.

If a pseudogene is transcribed in the opposite direction then its antisense RNA could interfere with the expression of the normal gene. Wells gives us three examples of this phenomenon: one famous one from snails (1999), one from mouse oocytes (2008), and one from rice (2009). I don't know whether all these results have been confirmed but even if they have it doesn't amount to much. All kinds of strange things happen in biology and the fact that a few pseudogenes might have acquired a regulatory function isn't shocking. What about the other 20,000 pseudogenes?

Pseudogene Enhancement of Gene Expression


& Junk DNA
Well, there's always the possibility that pseudogenes could enhance gene expression. The next section is "Pseudogene Enhancement of Gene Expression." Jonathan Wells begins this section with a description of the results on the mouse Mkrn-1-p1 pseudogene. The authors of this famous 2003 Nature paper claim that transcripts from the pseudogene protect the functional mRNA by shielding it from degradation. The title of their paper is "An expressed pseudogene regulates the messenger-RNA stability of its homologous coding gene" (Hirotsune et al., 2003).

Wells devotes three paragraphs to this important paper. There's only one slight problem. This work has been discredited in a 2006 PNAS paper with the title "The putatively functional Mkrn-1-p1 pseudogene is neither expressed nor imprinted nor does it regulate its source in trans." (Gray et., 2006) Oops!

Wells knows about this 2006 paper because he discusses it in Chapter 8 when he attacks the defenders of junk DNA. In chapter 5 he adds the following remark in parentheses, "Other biologists later challenged the Makorin-1 pseudogene results, which remain controversial." I think this is the only time when he mentions any legitimate scientific controversy.

There are three other examples of pseudogenes that might have an enhancement function: one from plants and two from humans. I don't know if these studies have been confirmed but even if they have they don't have much of an impact on the possible functions of the remaining 20,000 pseudogenes.

Sequence Conservation

The only significant evidence of widespread functionality of pseudogenes comes from two studies on sequence conservation. Wells covers this in a one-page section on "Sequence Conservation." The studies purport to show that pseudogene sequences are much more conserved than expected if they are really junk DNA. These studies have not been reproduced, as far as I know, and they fly in the face of much evidence to the contrary—evidence that Wells forgets to mention.

The first paper is a review by Balakirev and Ayala (2003). They review the possible functions of some pseudogenes in Drosophila and mammals. Some of them show evidence of sequence conservation. They conclude that most pseudogenes are probably functional. A study published that same year looked at all the known pseudogenes in the human genome and concluded that 95% of them evolved as though they had no function (i.e. they were not conserved) (Torrents et al., 2003)

The second paper that Wells mentions is Khachane and Harrison (2009). They identify 68 human pseudogenes whose sequences appear to be conserved in at least two other mammals. These are good candidates for functional genes.

The strange thing about this argument is that Wells doesn't believe in common descent so the evidence of sequence conservation really shouldn't have any meaning for him. Nevertheless, he says ...
How odd! As we saw in Chapter 2, Kenneth Miller, Richard Dawkins, Douglas Futuyma, Michael Shermer, Jerry Coyne and John Avise argue that pseudogenes confirm Darwinism because they are non-functional. But if we assume that Darwinism is true and then compare the DNA of unrelated organisms, sequence similarities imply that many of their pseudogenes are functional. So nonfunction supposedly implies Darwinism, but Darwinism plus sequence conservation implies function. When it comes to conserved pseudogenes, it seems, Darwinism saws off the very branch on which it sits.
For the record, if the majority of pseudogenes really are more conserved than expected from random mutations and fixation by random genetic drift then this would, indeed, be evidence that something is going on. Maybe they do have a function we don't know about. I don't think the evidence points in this direction at all—in fact much of the evidence contradicts it. Balakirov and Ayala (2003) are just speculating. I prefer the evidence of Torrents et al. (2003) suggesting that only a small number of potential pseudogenes have a function. This is consistent with the results of Khachane and Harrison (2009).

[If all 1,000 presumed pseudogenes turned out to be real genes then this moves about 0.06% of the genome from the junk category to the functional category. This isn't enough to save the IDiots.]

The Vitamin C Pseudogene

Finally, there's a section I haven't covered. It's titled "The Vitamin C Pseudogene." Wells has to address this particular pseudogene because it's the one that comes up most often when evolutionary biologists (e.g. Ken Miller and Jerry Coyne) criticize Intelligent Design Creationism. Here's what Wells says,
The evidence is not as straightforward as Miller and Coyne make it out to be, however, and their argument is ultimately circular. In any case, common ancestry and intelligent design are two different issues, and the vitamin C story would take us on a detour from the issue of junk DNA that's the focus of this book, so the details are omitted here and included in an appendix.
Which brings us to the Appendix: "The Vitamin C Pseudogene."

The main argument of scientists like Ken Miller and Jerry Coyne is not that the GULOP pseudogene exists. It's that the GULOP gene and its pseudogene are at the same location in the genomes of all mammals. In the primate lineage this gene is non-functional due to a number of mutations that make it impossible to produce a functional protein. Some of the same deactivating mutations are found in related species such as humans and chimpanzees. This suggests strongly that the non-functional pseudogene was inherited from a common ancestor. How do Intelligent Design Creationists deal with this evidence?

How does Wells respond?
... intelligent design and common ancestry are two different issues. Major ID proponents pointed this out before Miller wrote his book....Although some ID proponents (including me) question universal common ancestry on empirical grounds (as do some evolutionary biologists), intelligent design is not necessarily inconsistent with common ancestry.
I'm not sure what this means. Does it mean that people like Wells are completely bamboozled by this data since they can't refute either the evidence of common descent or the evidence of bad design? Other IDiots, like Michael Behe, only have to explain the bad design?

Jerry Coyne has published a similar argument but Wells attacks him on two fronts. First, he claims that human and chimpanzee Y chromosomes differ by 60 million nucleotide substitutions. If they really have a common ancestor then one would expect much greater sequence similarity. According to Wells, "If similarities in the vitamin C pseudogene are evidence for common ancestry, then differences in the Y chromosome are presumably evidence against it."

The Y chromosome paper is Hughes et al. (2010). Their results show that in orthologous regions of the Y chromosomes the human and chimp sequences are 98.3% identical. However, the chimp and human chromosomes differ in other regions because of large inserts and deletions. This is still evidence of common ancestry.

As usual, Wells is wanting to have his cake and eat it too.

The second attack is based on a number of quibbles. Coyne said that all primates need vitamin C in their diets but Wells points out that prosimians are primates and they can make vitamin C. Furthermore, according to Wells the requirement for vitamin C has only been established in nine species of monkeys. There are 251 other species and we don't know if they need vitamin C. Not only that, Coyne claimed that all primates have the same single nucleotide deletion in their GULOP pseudogene but Wells is quick to point out that only five primate sequences have been published.

Put that in your pipe and smoke it, Jerry Coyne! I assume that Wells is completely incapable of answering the challenge that's been issued and that's why he resorts to red herrings.

Continuing with this shotgun approach we quickly encounter several other arguments that are designed to distract from the main topic.
  • "Miller and Coyne rely on speculations about the motives of the designer or creator that have no legitimate place in natural science." (I hope you turned off your irony meter before reading that.)
  • Miller and Coyne have not provided any evidence to justify their claim that the GLO pseudogene is completely nonfunctional.
  • (Turn off your irony meter!) Their argument is circular. The similarities in sequence between chimp and human pseudogenes could be due to natural selection. "To break the circle, Miller and Coyne would either have to establish the recent ancestry of humans and chimps on other grounds (but why then bother invoking the vitamin C pseudogene at all?), or they would first have to establish that the vitamin C pseudogene has no function whatsoever (but this is impossible). So their argument not only fails to refute ID, but it also fails to establish that humans and chimps are descended from a common ancestor."
I feel a bit sorry for Ken Miller and Jerry Coyne. If this is the best the IDiots can do then why bother trying to argue with them in the first place?

Thus endeth Chapter 5.

Gray TA, Wilson A, Fortin PJ, Nicholls RD. (2006) 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 103:12039-12044. [PDF]

Hirotsune, S., Yoshida, N., Chen, A., Garrett, L., Sugiyama, F., Takahashi, S., Yagami, K., Wynshaw-Boris, A., and Yoshiki, A. (2003) An expressed pseudogene regulates the messenger-RNA stability of its homologous coding gene. Nature 423:91-6. [PDF]

Hughes, J.F., Skaletsky, H., Pyntikova, T., Graves, T.A., van Daalen, S.K., Minx, P.J., Fulton, R.S., McGrath, S.D., Locke, D.P., Friedman, C., Trask, B.J., Mardis, E.R., Warren, W.C., Repping, S., Rozen, S., Wilson, R.K., and Page, D.C. (2010) Chimpanzee and human Y chromosomes are remarkably divergent in structure and gene content. Nature 463:536-539. [Nature]

Khachane, A.N., and Harrison, P.M. (2009) Assessing the genomic evidence for conserved transcribed pseudogenes under selection. BMC Genomics 15:435-449. [PDF]

Torrents, D., Suyama, M., Zdobnov, E., and Bork, P.. (2003) A genome-wide survey of human pseudogenes. Genome Res. 13:2559-2567. [PDF]

Wednesday, May 25, 2011

Junk & Jonathan: Part 7—Chapter 4

This is part 7 of my review of The Myth of Junk DNA. For a list of other postings on this topic see the link to Genomes & Junk DNA in the "theme box" below or in the sidebar under "Themes."

The title of Chapter 4 is Introns and the Splicing Code. It opens with a brief description of eukaryotic genes and alternative splicing. Here's a better description of splicing for those who want a quick refresher: RNA Splicing: Introns and Exons. Alternative splicing is when a transcript can be spliced in at least two different ways to produce 2 distinct mRNAs. Each of them will make a different, but related, protein. The process has been known for thirty years and the mechanism is well-understood. It's described very well in a Wikipedia article: Alternative Splicing.

Here's some important background information from Junk in Your Genome: Protein-Encoding Genes.

The minimum size of a eukaryotic intron is less than 50 bp. For a typical mammalian intron, the essential sequences in the introns are: the 5′ splice site (~10 bp); the 3′ splice site (~30 bp): the branch site (~10 bp); and enough additional RNA to form a loop (~30 bp). This gives a total of 80 bp of essential sequence per intron or 20,500 × 7.2 × 80 = 11.8 Mb. Thus, 0.37% of the genome is essential because it contains sequences for processing RNA.
In other words, assuming that introns aren't all junk we can estimate how much of the intron sequence is essential for it's function by taking into account the known regulatory sequences and the amount needed to form a loop.

The rest of an intron sequence may be junk. If it is, then we would expect to see two things.
  • Considerable variation is intron size from species to species.
  • Frequent examples of transposons, endogenous retroviruses, and even other genes inserting into introns.
This is exactly what we see [Junk in Your Genome: Intron Size and Distribution]. There's no indication that intron sequences are conserved or essential.

Jonathan Wells explains that alternative splicing is important in some genes. He is correct. He then explains that there are sequences in introns that regulate alternative splicing. He's correct about that as well. We've been writing this up in the textbooks and teaching it in introductory biochemistry courses since early in the 1980s. The classic example is the determination of sex in Drosophila—it's largely controlled by alternative splicing and we know a great deal about which proteins bind to which sequences in the introns to promote or repress a given splice site [Sex in the fruit fly Drosophila melanogaster].

Nothing new here. We know about binding sites and we know that most of them are 10 bp or less. Their presence makes no significant difference in our calculations of junk DNA. I get the distinct impression that Wells and the other IDiots don't really understand splicing and alternative splicing.

Here's a series of blog posts I did last year when Richard Sternberg tried to pretend that he knew something about molecular biology and alternative splicing. Later on, Jonathan Wells weighs in to try and help his friend but ends up showing that he too, is in way over his head.

Creationists, Introns, and Fairly Tales

IDiots Do Arithmetic a Second Time - Same Result

Jonathan Wells Weighs in on Alternative Splicing

Having "proven" that something like 0.03% of our genome may not be junk, Wells then goes on to describe other sequences that are found in introns. Some of these are regulatory sequences or enhancers. These aren't common, but they do exist. They're usually located in the 5′ intron and they are often associated with alternative transcription start sites. The total amount of non-junk DNA due to regulatory sequences has already been taken into account in my calculations (Junk in Your Genome: Protein-Encoding Genes) and it doesn't matter whether these regulatory sequences are intergenic or included within an intron.


& Junk DNA
Wells also notes that many genes for small RNAs are located within introns. These include some of the genes for the splicing machinery, tRNA genes, snoRNA genes etc. He doesn't mention that introns are also loaded with Alu sequences and other transposable elements (mostly defective). The presence of the these insertions show us that cells don't discriminate between intron sequences that make up 25% of the genome and the remaining 65% that's mostly junk. They are all targets for inserting small genes and transposons. No surprises here.

Finally, on the last page of Chapter 4, Wells devotes two paragraphs to a genuine scientific argument. The idea is that long introns might be necessary to delay transcription. This idea has been around for a long time. It was originally proposed over 25 years ago as an explanation for the long introns found in Drosophila HOX genes, especially Ubx.

If a gene has several long introns it can stretch out over 100 kb (100,000 bp). The typical RNA polymerase II elongation complex transcribes at a rate of 50 bp per second so it will take more than 30 minutes to transcribe these long genes. The idea is that the presence of long introns delays appearance of the regulatory proteins during development. This seems unlikely because there are many other, more efficient, ways of regulating gene expression. As a matter of fact, the argument can be easily turned upside down.

Genes that need to be transcribed quickly have very short introns or none at all. The heat shock inducible genes, for example, don't even have introns. These genes need to be expressed rapidly when a cell encounters stressful conditions. Their non-inducible homologues all have respectable introns so it looks like there has been selection for losing introns in these genes.

Similarly, there are often testes specific genes than lack introns. The supposition is that these variant family members have lost introns so they can be quickly transcribed during spermatogenesis. The globin genes have relatively small introns and they are also expressed at a high rate in erythroblasts.

Genes that are infrequently transcribed tend to accumulate large introns. This includes most developmentally regulated transcription factors that only need to produce a small number of proteins at a specific time in the life of the organism. These observations are consistent with the idea that excess junk in intron sequences is removed when necessary. It's actually evidence that those sequences are junk.

So far we covered the evidence of probable function in Chapter 3 and seen that Wells does not critically examine the data on pervasive transcription but simply assumes it is correct. He then makes the unsubstantiated claim that evidence of transcription is evidence of function. He's wrong about the claim that most of our genome is transcirbed and he's wrong to assume that all transcripts are functional. Nothing in that chapter supported his claim that junk DNA is a myth.

In this chapter we see the first evidence for specific functions of noncoding DNA. The presence of regulatory sequences in introns has been well known for decades and it has no impact on the estimates of junk DNA. The idea that big introns might be adaptive regardless of sequence is possible but not reasonable. In fact, the evidence suggests strongly that big introns full of junk DNA can be detrimental in some cases. Nothing in Chapter 4 provides convincing evidence that junk DNA is a myth.

What about pseudogenes? Are they a myth? That's covered in Chapter 5.

A note about references
The IDiots are promoting this book by bragging about multiple references that challenge the concept of junk DNA [Jonathan Wells offers over 600 references to recent peer-reviewed literature]. Chapters 1 and 2 were introductions to the problem. They had a total of 51 references. Chapter 3 had 62 references but, as we have seen, they don't add up to a convincing case. There were plenty of references that should have been included if a scientific case was going to be made. Chapter 4 has 63 references but only three of them address a substantive argument against junk DNA in introns. All three make the same point; namely that long introns delay transcription.

That's a total of 176 references so far with nothing much to show for them. There are 432 references in the rest of the book. There are 26 references to known IDiots including 8 references to the work of Jonathan Wells.

Tuesday, May 24, 2011

Junk & Jonathan: Part 6—Chapter 3

This is part 6 of my review of The Myth of Junk DNA. For a list of other postings on this topic see the link to Genomes & Junk DNA in the "theme box" below or in the sidebar under "Themes."

We learn in Chapter 9 that Wells has two categories of evidence against junk DNA. The first covers evidence that sequences probably have a function and the second covers specific known examples of functional sequences. In the first category there are two lines of evidence: transcription and conservation. Both of them are covered in Chapter 3 making this one of the most important chapters in the book. The remaining category of specific examples is described in Chapters 4-7.

The title of Chapter 3 is Most DNA Is Transcribed into RNA. As you might have anticipated, the focus of Wells' discussion is the ENCODE pilot project that detected abundant transcription in the 1% of the genome that they analyzed (ENCODE Project Consortium, 2007). Their results suggest that most of the genome is transcribed. Other studies support this idea and show that transcripts often overlap and many of them come from the opposite strand in a gene giving rise to antisense RNAs.

The original Nature paper says,
... our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another.
The authors of these studies firmly believe that evidence of transcription is evidence of function. This has even led some of them to propose a new definition of a gene [see What is a gene, post-ENCODE?]. There's no doubt that many molecular biologists take this data to mean that most of our genome has a function and that's the same point that Wells makes in his book. It's evidence against junk DNA.

What are these transcripts doing? Wells devotes a section to "Specific Functions of Non-Protein-Coding RNAs." These RNAs may be news to most readers but they are well known to biochemists and molecular biologists. This is not the place to describe all the known functional non-coding RNAs but keep in mind that there are three main categories: ribosomal RNA (rRNA), transfer RNA (tRNA), and a heterogeneous category called small RNAs. There are dozens of different kinds of small RNAs including unique ones such as the 7SL RNA of signal recognition factor, the P1 RNA of RNAse P and the guide RNA in telomerase. Other categories include the spliceosome RNAs, snoRNAs, piRNAs, siRNAs, and miRNAs. These RNAs have been studied for decades. It's important to note that the confirmed examples are transcribed from genes that make up less than 1% of the genome.

One interesting category is called "long noncoding RNAs" or lncRNAs. As the name implies, these RNAs are longer that the typical small RNAs. Their functions, if any, are largely unknown although a few have been characterized. If we add up all the genes for these RNAs and assume they are functional it will account for about 0.1% of the genome so this isn't an important category in the discussion about junk DNA.


& Junk DNA
So, we're left with a puzzle. If more than 90% of the genome is transcribed but we only know about a small number of functional RNAs then what about the rest?

Opponents of junk DNA—both creationists and scientists—would have you believe that there's a lot we don't know about genomes and RNA. They believe that we will eventually find functions for all this RNA and prove that the DNA that produces them isn't junk. This is a genuine scientific controversy. What do their scientific opponents (I am one) say about the ENCODE result?

Criticisms of the ENCODE analysis take two forms ...
  • The data is wrong and only a small fraction of the genome is transcribed
  • The data is mostly correct but the transcription is spurious and accidental. Most of the products are junk RNA.
Criticisms of the Data

Several papers have appeared that call into question the techniques used by the ENCODE consortium. They claim that many of the identified transcribed regions are artifacts. This is especially true of the repetitive regions of the genome that make up more than half of the total content. If any one of these regions is transcribed then the transcript will likely hybridize to the remaining repeats giving a false impression of the amount of DNA that is actually transcribed.

Of course, Wells doesn't mention any of these criticisms in Chapter 3. In fact, he implies that every published paper is completely accurate in spite of the fact that most of them have never been replicated and many have been challenged by subsequent work. The readers of The Myth of Junk DNA will assume, intentionally or otherwise, that if a paper appears in the scientific literature it must be true.

But criticism of the ENCODE results are so widespread that they can't be ignored so Wells is forced to deal with them in Chapter 8. (Why not in Chapter 3 when they are first mentioned?) In particular, Wells has to address the van Bakel et al. (2010) paper from Tim Hughes' lab here in Toronto. This paper was widely discussed when it came out last year [see: Junk RNA or Imaginary RNA?]. We'll deal with it when I cover Chapter 9 but, suffice to say, Wells dismisses the criticism.

Criticisms of the Interpretation

The other form of criticism focuses on the interpretation of the data rather than its accuracy. Most of us who teach transcription take pains to point out to our students that RNA polymerase binds non-specifically to DNA and that much of this binding will result in spurious transcription at a very low frequency. This is exactly what we expect from a knowledge of transcription initiation [How RNA Polymerase Binds to DNA]. The ENCODE data shows that most of the genome is "transcribed" at a frequency of once every few generations (or days) and this is exactly what we expect from spurious transcription. The RNAs are non-functional accidents due to the sloppiness of the process [Useful RNAs?].

Wells doesn't mention any of this. I don't know if that's because he's ignorant of the basic biochemistry and hasn't read the papers or whether he is deliberately trying to mislead his readers. It's probably a bit of both.

It's not as if this is some secret known only to the experts. The possibility of spurious transcription has come up frequently in the scientific literature in the past few years. For example, Guttmann et al. (2009) write,
Genomic projects over the past decade have used shotgun sequencing and microarray hybridization to obtain evidence for many thousands of additional non-coding transcripts in mammals. Although the number of transcripts has grown, so too have the doubts as to whether most are biologically functional. The main concern was raised by the observation that most of the intergenic transcripts show little to no evolutionary conservation. Strictly speaking, the absence of evolutionary conservation cannot prove the absence of function. But the remarkably low rate of conservation seen in the current catalogues of large non-coding transcripts (less than 5% of cases) is unprecedented and would require that each mammalian clade evolves its own distinct repertoire of non-coding transcripts. Instead, the data suggest that the current catalogues may consist largely of transcriptional noise, with a minority of bona fide functional lincRNAs hidden amid this background.
This paper is in the Wells reference list so we know that he has read it.

What these authors are saying is that the data is consistent with spurious transcription (noise). Part of the evidence is the lack of any sequence conservation among the transcripts. It's as though they were mostly derived from junk DNA.

Sequence Conservation

Recall that the purpose of Chapter 3 is to show that junk DNA is probably functional. The first part of the chapter reportedly shows that most of our genome is transcribed. The second part addresses sequence conservation.

Here's what Wells says about sequence conservation.
Widespread transcription of non-protein-coding DNA suggests that the RNAs produced from such DNA might serve biological functions. Ironically, the suggestion that much non-protein-coding DNA might be functional also comes from evolutionary theory. If two lineages diverge from a common ancestor that possesses regions of non-protein-coding DNA, and these regions are really nonfunctional, then they will accumulate random mutations that are not weeded out by natural selection. Many generations later, the sequences of the corresponding non-protein-coding regions in the two descendant lineages will probably be very different. [Due to fixation by random genetic drift—LAM] On the other hand, if the original non-protein-coding DNA was functional, then natural selection will tend to weed out mutations affecting that function. Many generations later, the sequences of the corresponding non-protein-coding regions in the two descendant lineages will still be similar. (In evolutionary terminology, the sequences will be "conserved.") Turning the logic around, Darwinian theory implies that if evolutionarily divergent organisms share similar non-protein-coding DNA sequences, those sequences are probably functional.
Wells then references a few papers that have detected such conserved sequences, including the Guttmann et al. (2009) paper mentioned above. They found "over a thousand highly conserved large non-coding RNAs in mammals." Indeed they did, and this is strong evidence of function.1 Every biochemist and molecular biologist will agree. One thousand lncRNAs represent 0.08% of the genome. The sum total of all other conserved sequences is also less than 1%. Wells forgets to mention this in his book. He also forgets to mention the other point that Guttman et al. make; namely, that the lack of sequence conservation suggests that the vast majority of transcripts are non-functional. (Oops!)

There's irony here. We know that the sequences of junk DNA are not conserved and this is taken as evidence (not conclusive) that the DNA is non-functional. The genetic load argument makes the same point. We know that the vast majority of spurious RNA transcripts are also not conserved from species to species and this strongly suggests that those RNAs are not functional. Wells ignores this point entirely—it never comes up anywhere in his book. On the other hand, when a small percentage of DNA (and transcripts) are conserved, this gets prominent mention.

Wells doesn't believe in common ancestry so he doesn't believe that sequences are "conserved." (Presumably they reflect common design or something like that.) Nevertheless, when an evolutionary argument of conservation suits his purpose he's happy to invoke it, while, at the same time, ignoring the far more important argument about lack of conservation of the vast majority of spurious transcripts. Isn't that strange behavior?

The bottom line hear is that Jonathan Wells is correct to point to the ENCODE data as a problem for junk DNA proponents. This is part of the ongoing scientific controversy over the amount of junk in our genome. Where I fault Wells is his failure to explain to his readers that this is disputed data and interpretation. There's no slam-dunk case for function here. In fact, the tide seems to turning more and more against the original interpretation of the data. Most knowledgeable biochemists and molecular biologists do not believe that >90% of our genome is transcribed to produce functional RNAs.

UPDATE: How much of the genome do we expect to be transcribed on a regular basis? Protein-encoding genes account for about 30% of the genome, including introns (mostly junk). They will be transcribed. Other genes produce functional RNAs and together they cover about 3% of the genome. Thus, we expect that roughly a third of the genome will be transcribed at some time during development. We also expect that a lot more of the genome will be transcribed on rare occasions just because of spurious (accidental) transcription initiation. This doesn't count. Some pseudogenes, defective transposons, and endogenous retroviruses have retained the ability to be transcribed on a regular basis. This may account for another 1-2% of the genome. They produce junk RNA.

1. Conservation is not proof of function. In an effort to test this hypothesis Nöbrega et al. (2004) deleted two large regions of the mouse genome containing large numbers of sequences corresponding to conserved non-coding RNAs. They found that the mice with the deleted regions showed no phenotypic effects indicating that the DNA was junk. Jonathan Wells forgot to mention this experiment in his book.

Guttman, M. et al. (2009) Chromatin signature reveals over a thousand highly conserved non-coding RNAs in mammals. Nature 458:223-227. [NIH Public Access]

Nörega, M.A., Zhu, Y., Plajzer-Frick, I., Afzal, V. and Rubin, E.M. (2004) Megabase deletions of gene deserts result in viable mice. Nature 431:988-993. [Nature]

The ENCODE Project Consortium (2007) Nature 447:799-816. [PDF]

Monday, May 23, 2011

A Poll: How Much of the Human Genome Is Junk?

It's time for another poll. Please answer the question in the sidebar.

Junk & Jonathan: Part 5—Chapter 2

This is part of my review of The Myth of Junk DNA. For a list of other postings on this topic see the link to Genomes & Junk DNA in the "theme box" below or in the sidebar under "Themes."

Chapter 2 is Junk DNA: The Last Icon of Evolution? It's mostly an explanation of how the concept of junk DNA fits into evolution. According to Wells, Darwin's theory of evolution by natural selection explains how living things descend with modification from a common ancestor. (Recall that Wells rejects common ancestry.) Wells explains that Darwin's original idea has been extended with the discovery of DNA. He describes "neo-Darwinism" like this ...
According to neo-Darwinism, traits are passed on by genes that reside on microscopic thread-like structures in the cells called chromosomes, and new traits arise from accidental genetic mutations.
In order to clear up any confusion, Wells tells us that, "... I will use "Darwinism" in the rest of the book to mean both Darwin's theory and neo-Darwinism" (p. 19). This is important since it's clear that he's talking about the theory of natural selection when he talks about Darwinism or neo-Darwinism.

Wells describes how Ohno coined the term "junk" DNA in 1972 then quotes Richard Dawkins as a supporter of junk. He states his belief that a couple of papers on selfish DNA in 1980 were taken as evidence of junk. He concludes that ...
... some biologists were skeptical of the notion of "junk DNA" from the very beginning—though most accepted it.
Wells fails to distinguish between those biologists who recognize the existence of junk DNA (e.g. pseudogenes) and those who thought that most of our genome is junk. I still believe that only a minority of biologists think that most our genome is junk. I also think that many biologists make a distinction between "junk" and "selfish." I know I do. In my mind "selfish" DNA, such as active transposons or endogenous retroviruses, isn't junk.

Next comes a couple of pages under the subheading "Using Junk DNA as Evidence for Darwinism and Against Intelligent Design." The usual suspects are mentioned. He quotes Ken Miller, Douglas Futuyma, Michael Shermer, Francis Collins, Phil Kitcher, Jerry Coyne, and John Avise. Although their emphasis varies, they all make the point that the presence of junk DNA in our genome is not consistent with intelligent design. It is, however, consistent with evolution (but not natural selection).


& Junk DNA
It's important to note that biologists don't, with rare exceptions, claim that the presence of junk DNA is evidence for Darwinism or evolution. It's consistent with our understanding of modern evolutionary theory but compact genomes with no junk would also be consistent with evolution, especially evolution by natural selection.

Most of these writers are pointing out how difficult it is for Intelligent Design Creationists to make their case in light of massive amounts of junk in our genome. They are mostly arguing against design and not for evolution.1 This point will come up again in Chapter 10.

Wells concludes with ...
The arguments by Dawkins, Miller, Shermer, Collins, Kitcher, Coyne and Avise rest on the assumption that most non-coding DNA is junk, without any significant biological function. Yet a virtual flood of recent evidence shows that they are mistaken: Much of the DNA they claim to be "junk" actually performs important functions in living cells.
The stage is set. In the rest of the book, Jonathan Wells will try and convince us that most of the DNA in our genome is not junk. Pay attention 'cause it's important to keep the main focus of the dispute in center stage. What the scientists are saying is that there's a lot of junk in our genome and, in order to blunt that attack on design, Wells has to show that there's not very much junk DNA (perhaps none). It won't be sufficient to show that a few percent here and there aren't junk. Any amount of junk DNA is a threat to the basic concept of intelligent design. That's why the IDiots are so worried.

1. I often make the same argument against adaptationists. Some of them see design by natural selection as the dominant feature of evolution but that's not what our genome tells us. There's no illusion of apparent design in our genome sequence.

Sunday, May 22, 2011

Junk & Jonathan: Part 4—Chapter 1

I received a copy of the book a few days ago and this is my first posting on its contents. For a list of other postings on this topic see the link to Genomes & Junk DNA in the "theme box" below or in the sidebar under "Themes."

This is a very small book. There's only 114 pages of text—it's more like a large pamphlet than a book. If I'd read it from front to back in one sitting it would only have taken an hour or so. But I couldn't read it in one go because nobody can put up with IDiot rhetoric for that long!

Chapter 1 is The Controversy over Darwinian Evolution. It has nothing to do with junk DNA.

Wells begins by telling his readers that evolution is a fact. By that he means "microevolution." Wells doesn't believe in macroevolution or common descent and he even challenges the evidence for speciation. As usual, he supports his claims with selected quotations from scientists.
Sixty year after Dobzansky wrote this, biologists had still not observed the origin of a new species ("speciation") by natural selection. In 1997, evolutionary biologist Keith Stewart Thomson wrote: "A matter of unfinished business for biologists is the identification of evolution's smoking gun," and "the smoking gun of evolution is speciation, not local adaptation and differentiation of populations."
Wells is telling his readers that as long as biologists have not directly observed a new species forming then speciation has not been demonstrated. This rules out all evidence from the fossil record and all evidence from molecular phylogeny. Nice trick.

Problem is, there's lots of lots of evidence for speciation, including some examples where speciation has been caught in the act. Wells, like most IDiots, doesn't understand how evolution works. He seems to think that new species will form overnight and that all biologist have to do is keep their eyes open and record the examples.

I don't know for sure whether Wells intends to emphasize speciation by natural selection when he claims that, "biologists had still not observed the origin of a new species ("speciation") by natural selection." If that's his intent then it's true that there are very few examples of true speciation (biological species concept) that can be attributed directly to natural selection. As Jerry Coyne points out, reproductive isolation is mostly due to accident (random genetic drift) and not natural selection [The Cause of Speciation]. That's in line with modern evolutionary theory and Coyne should know because he's one of the world's leading experts on speciation. [UPDATE: Coyne and some commenters have corrected me. Coyne actually does think that most speciation is due to natural selection. I'll stick with Futuyma as my authority. He's much more open to the idea of speciation by random genetic drift (Evolution 2nd ed. p. 447)]

There are two possibilities here. Either Wells is deliberately misleading his readers by emphasizing that speciation must occur by natural selection or he's ignorant of modern evolutionary theory. Since most IDiots have a concept of evolution that dates back to the nineteenth century, I'll go with the second explanation. However, there's almost certainly an element of deception in his remarks since Jonathan Wells has a long history of deliberately misrepresenting evolution.


& Junk DNA
So, Wells is dead wrong about the first point in his book. There's abundant evidence of speciation (and macroevolution) and, furthermore, modern evolutionary theory does not attribute speciation exclusively to adaptation (i.e. there's more to evolution than Darwinism).

The importance of Wells' rejection of macroevolution will become obvious later on in the book when he argues that Intelligent Design Creationism does not rule out common ancestry. He agrees that someone like Michael Behe can believe in common descent and still be a card-carrying IDiot.

By the way, Wells is clever enough to cover his bases in case speciation is ever observed.
Of course, even if scientists eventually observe the origin of a new species by natural selection, the observation would not mean that natural selection can also explain the origin of significantly new organs or body plans. But the fact that scientists have not observed even the first step in macroevolution means that "evolution's smoking gun" is still missing.
The rest of the chapter (three pages) is a re-hash of arguments Wells made in Icons of Evolution and elsewhere.
  • The Cambrian Explosion "contradicts Darwin's theory that major differences should arise only after millions of years of evolution ...."
  • Molecular evolution isn't accurate: "molecular evidence is plagued with inconsistencies." The rejection of molecular evidence as unreliable is going to cause problems for Wells later on since he relies on it for some of his arguments about junk DNA. As usual, the IDiots want to have their cake and eat it too.
  • Homology is a circular argument, according to Wells, so you can't use homology as evidence for evolution. That's correct. Similarity is the evidence and homology is the conclusion. This flaw in Wells' reasoning has been pointed out to him repeatedly over the past decade but he ignores all criticism and continues to use arguments that have been refuted.
  • The Haeckel drawings were fakes and, "The truth is that vertebrate embryos start out looking very different from each other, then they converge somewhat in appearance midway through development before diverging as they mature." This has nothing to do with junk DNA so I won't discuss the massive amount of embryological evidence for evolution.
Wells closes with,
So microevolution is a fact, supported by overwhelming evidence, but macroevolution remains an assumption, illustrated with icons that misrepresent the evidence or rely on circular reasoning. The icons are not science, but myth.
This sets the tone for the rest of the book. Even though it is filled with references to the scientific literature there's never any discussion of alternative hypotheses or conflicting data. This is not a book where the author wants to inform his readers about the exciting controversies and conflicts within science. This is a book where the author wants to promote creationism by attacking and misrepresenting evolution using faulty logic and untruths.

The next paragraph is quite interesting. He invokes the beliefs of Americans as support for his claims. Apparently they're much more perceptive that the typical evolutionary biologist. (I wonder what he thinks of Australians and Europeans?)
This may be one reason why—despite the Darwinists' near-monopoly over science education—most Americans still reject the doctrine that human beings evolved from ape-like ancestors by unguided processes such as random variation and survival of the fittest.
I think this means that Wells also rejects common ancestry. If so, it will mean that he can't use it to support any of his arguments later on in the book, right?

Finally, at the very end of the chapter we get to the point,
In the 1950s, neo-Darwinists equated genes with DNA sequences and assumed that their biological significance lay in the proteins the encoded. But when molecular biologists discovered in the 1970s that most of our DNA does not code for proteins, neo-Darwinists called non-protein-coding DNA "junk" and attributed it to molecular accidents that have accumulated in the course of evolution. Like peppered moths, Galapagos finches, Darwin's Tree of Life, homology in vertebrate limbs, and Haeckel's embryos, "junk DNA" has become an icon of evolution. But is it science of myth?
I've discussed Wells' ignorance of history in previous postings but, for the record, here are the facts.
  • By the 1970s molecular biologist were well aware of the fact that non-protein coding genes existed (e.g. ribosomal RNA genes, tRNA genes etc.)
  • By the 1970s molecular biologists knew of several functions of DNA sequences that weren't genes. Origins of replication and regulatory sequences were well-known but there were others.
  • Even in the 1970s no knowledgeable molecular biologist could ever defend the idea that all non-coding DNA was junk. (It's true that there were some stupid scientists who weren't aware of tRNA genes and regulatory sequences and made silly statement because of their ignorance but they don't count.)
  • By the 1970s junk DNA was a fact. The scientific controversy was over how much of our genome is junk. Is it the majority or only a small percentage?
  • By the 1970s knowledgeable evolutionary biologists were well aware of the fact that most of our genome was mutating and evolving as though most changes were neutral (genetic load arguments). This didn't mean that most of our genome was junk but it did mean that the sequence couldn't be important or we would never be able to tolerate the genetic load. This was not common knowledge among biologists—still isn't.
  • By the 1970s most molecular biologists were aware of the so-called "C-value paradox" where very closely related species have very different genome sizes. They correctly interpreted this to mean that the species with the large genomes probably didn't need all that extra DNA. (Up until now, Intelligent Design Creationists have not offered a reasonable answer to The Onion Test. Wells tries on Chapter 8.)
  • The proponents of large amounts of junk DNA in our genome would hardly ever have referred to themselves as "Darwinist" or "neo-Darwinists." In fact, they tended to be among those evolutionary biologists who opposed adaptationism and favored Neutral Theory and random genetic drift. Pluralist concepts were much more compatible with the idea of significant amounts of junk DNA than strict "Darwinist" interpretations of genome evolution.

Monday, May 16, 2011

See the IDiots Gloat over Jonathan Wells

This is part of my discussion about The Myth of Junk DNA by Jonathan Wells. I still haven't read the book—it won't be released in Canada until May 31st.

Over on Evolution News & Views (sic) David Klinghoffer is already counting his chickens [Junk DNA and the Darwinist Response so Far].
Over the weekend, Jonathan Wells's The Myth of Junk DNA broke into the top five on Amazon's list of books dealing with genetics -- a list normally dominated at its pinnacle by various editions of Richard Dawkins' The Selfish Gene. Not bad, Jonathan.
Not bad indeed, except I can't tell if it's true. When I check the top selling recently published books I don't see The Myth of Junk DNA in the top five. Never mind, I'm sure there will be many skeptics like me who will buy the book just for a good laugh.

UPDATE: The latest information shows that Wells' book is ranked 23rd under "Genetics." I'm sure the IDiots just made a simple arithmetic error when they said it had broken into the top five.
The juxtaposition with Dawkins' Selfish Gene is appropriate, notwithstanding the demurrals of biochemist Larry Moran et al. Dawkins and other Darwinists, such as Jerry Coyne, have indeed posited that neo-Darwinian theory predicts that swaths of the genome will turn out to be functionless junk. The Junk DNA argument has been a pillar of the Darwin Lobby's efforts to seduce public opinion and influence public policy. Professor Moran wants to imagine that Dawkins never held that neo-Darwinism predicts junk DNA. But that's not how other Darwinists see it. (Compare, for example, Dennett's Darwin's Dangerous Idea, page 316.)
The IDiots have a bit of a problem. In order to make this book look important they have to first establish that the concept of abundant junk DNA in our genome was a "pillar" of support for evolution. That's hard to do when their understanding of evolution is so flawed that they don't see the difference between "Darwinism" and evolution by random genetic drift.

Their claim that evolutionary theory PREDICTED the presence of huge amounts of junk DNA in our genome is just plain false. They been told this but they keep repeating their error. There's a word for that kind of behavior.

It's easy to see how they got confused. It's because they're IDiots. It's partly because they don't understand that an argument for inheritance of a few pseudogenes is not the same as an argument that more than 50% of our genome is junk. There are plenty of scientists who will use the pseudogene argument to challenge Intelligent Design Creationism but who don't believe that MOST of our genome is junk.

It's also partly because the IDiots don't know the difference between selfish DNA and junk. Here's what Daniel Dennett says on page 316 of Darwin's Dangerous Idea.
The presence of functionless DNA in the genome is no longer regarded as a puzzle. Dawkins (1976) selfish-gene theory predicts it, and elaborations on the idea of "selfish DNA" were simultaneously developed by Doolittle and Sapeinza (1980) and Orgel and Crick (1980) (see Dawkins 1982, ch. 9, for the details).
Selfish DNA is not junk DNA. The classic examples of selfish DNA are active transposons and integrated viruses. These bits of DNA have a function—even if it's only to propagate themselves. As you can see from my summary [What's in Your Genome?]. I don't count them as junk.

It's remarkable that Klinghoffer quotes Chapter 9 of The Extended Phenotype (1982) since Dawkins take pains to point out that much of the junk DNA in our genome could have a function. This is exactly the sort of skepticism one would expect from a Darwinist.
This does not mean, however, that the so-called junk DNA is not subject to natural selection. Various 'functions' for it have been proposed, where 'function' means adaptive benefit to the organism.
He goes on to describe several of the proposals that are common arguments against junk DNA. If the DNA has a function and it's adaptive, then it is not junk. Selfish DNA is not junk.

Let's be very clear about one thing. The scientific dispute is not over the existence of junk DNA. That's well established. The dispute is over how much of our genome is junk (DNA with no function). In order to refute the idea that MOST of our genome is junk, you have to show that most of it has a function of some sort. I'm looking forward to Jonathan Wells' book where he is going to prove to us that >50% of our genome has a function. (Not holding my breath!)
So far, with none of them having actually read the book (though P.Z. Myers threatens to do so), the Darwin apologists' response to The Myth of Junk DNA has followed along four lines of defense.

1) The usual insults. In his blog Larry Moran of the Department of Biochemistry at the University of Toronto, a grown man and from the looks of him not a young one either, repetitively derides Jonathan as an "IDiot." (How embarrassing for this mature gentleman, you might think. Can you imagine Jonathan Wells or anyone else prominent in the ID community replying in kind, designating Professor Moran as "Larry Moron" or similar? The question is self-answering and tells you a lot about how desperation kindles anger among these people.)
You know, there's one sure way to prove you're not an idiot. The IDiots have been trying for over twenty years to show that they understand science. I'll gladly stop calling them idiots as soon as they deserve it.

Speaking of insults. There's one sure way to ensure that you aren't going to be insulted and that's to stop calling evolutionary biologists "Darwinists" and stop saying that they don't understand their own discipline. I find that extremely insulting and I'm not going to refrain from responding in kind.

I don't know what Jonathan Wells is going to say in his latest book but here's a few examples of insults in Icons of Evolution.
There is a pattern here, and it demands an explanation. Instead of continually testing their theory against the evidence, as scientists are supposed to do, some Darwinists consistently ignore, explain away, or misrepresent the biological facts in order to promote their theory. One isolate example of such behavior might be due simply to overzealousness. Maybe even two. But ten? Year after year? (p. 230)

Fraud is a dirty word, and it should not be used lightly. In the cases described in this book, dogmatic promoters of Darwinism did not see themselves as deceivers. Yet they seriously distorted the evidence—often knowingly. If this is fraud when a stock promoter does it, what is it when a scientist does it? (p. 234)

If dogmatic promoters of Darwinian evolution were merely distorting the truth, that would be bad enough. But they haven't stopped there. They now dominate the biological sciences in the English-speaking world, and use their position of dominance to censor dissenting viewpoints. (p. 235)

The truth is that a surprising number of biologists quietly doubt or reject some of the grander claims of Darwinian evolution. But—at least in America—the must keep their mouths shut or risk condemnation, marginalization, and eventual expulsion from the scientific community. This happens infrequently, but often enough to remind everyone that the risk is real. (p. 239)
Klinghoffer continues with his four lines of defense that we "Darwinists" apparently use to defend the existence of abundant junk DNA (>50%) in our genome.
2) Denying that junk DNA ever figured preeminently in the Darwinist's quiver of arguments against design. Moran, for example, asserts, "There was never a time when knowledgeable molecular biologists equated 'junk' DNA and 'noncoding' DNA." Huh, that's strange. I'm not aware of anyone who has scientifically polled the community of professional biologists on the subject. But I do know that in the struggle for public opinion over the question of Darwin versus Design, junk DNA has again and again been employed, by all the most eminent protagonists on the Darwinian side, as a bludgeoning weapon against intelligent design. Never mind The Selfish Gene, in his most recent book, The Greatest Show on Earth (2009), Dawkins observed that "the greater part...of the genome might as well not be there, for all the difference it makes," and that this fact is "useful for...embarrassing creationists."

Similarly, in Why Evolution Is True (2009), Jerry Coyne offers it, again, as a "prediction" of neo-Darwinian theory that we'll find the genome littered with useless "vestigial genes."
I said that knowledgeable scientists never said that all non-coding DNA is junk. Klinghoffer says, blah, blah, blah, not even addressing my statement.

You can't make this stuff up. At every single opportunity the IDiots demonstrate that they deserve the title.
3) When not denying that junk DNA is a prime, staple argument for Darwin apologists, Professor Moran wants to have it the opposite way. In the same series of blog posts attacking "the IDiot" Jonathan Wells, Moran maintains his own belief that the genome is indeed overwhelmingly useless junk. "Some (I am one)," he writes, "still think that as much as 90 percent could be junk." He insists that "it's not sufficient to show that a few bits of repetitive DNA have gained a function in some species."

Dr. Moran's problem is that he has neither read Jonathan's book nor, it seems, followed the cascade of evidence from the scientific publications. It's a heck of a lot more than just "a few bits of repetitive DNA" that have been shown to be functional. In a brief (and enviably readable and accessible) 115-page book, Jonathan Wells offers over 600 references to recent peer-reviewed literature.

Twenty-five thousand studies further down the road from where we are now, no one knows how much of the genome will turn out to be truly functionless and therefore genuinely worthy of the appellation "junk." But for Darwinists, the speedily mounting evidence against junk DNA is an ominous portent. As Casey Luskin and others have put it, it's the trend that stands out prominently here, on which the likes of Larry Moran have so far been in denial.

& Junk DNA
I've tried and tried to get the IDiots to have a serious, scientific, discussion about the evidence for and against abundant junk DNA in our genome. Some of them have tried but their arguments soon degenerate into insults about my lack of knowledge of the scientific literature. This is in spite of the fact that I have dozens of postings on the subject over the past few years and nobody has ever shown that I've been ignorant of the science behind the controversy. We may disagree about the interpretation but that's not what I'm being accused of here.

As soon as I read the book I'll post a bunch of articles pointing out why it's wrong. That will give the IDiots, like Jonathan Wells, a chance to debate the points I make and show that he is right and I am wrong. I'm looking forward to it.
4) Finally, in my own small contribution to this debate, I made a facetious comment here about how the identification of Osama bin Laden's corpse by DNA fingerprinting, using his "junk DNA" as the media habitually referred to it, provided a welcome news hook for the publication of Jonathan's book. This provoked braying responses from the Darwin Lobby. For example, our journalist friend Lauri Lebo, challenged as ever in her reading-comprehension skills, somehow understood that I was saying the usefulness of non-coding DNA for this forensic purpose proved it isn't junk.

P.Z. Myers tried to show that the usefulness of non-coding DNA for genetic fingerprinting is another demonstration that the stuff really is junk, being "subject to random changes at a higher rate than coding DNA, because it is not subject to functional constraints."
Every now and them some IDiots get something right—even if it's just by accident. One example is when Klinghoffer describes his posting as "my own small contribution."
But whether "junk DNA" is functional is exactly the question at issue, isn't it? The fact that our DNA is pervasively transcribed, as Jonathan Wells points out in Chapter 3 of his book, itself suggests pervasive functionality. As has become clear, too, DNA may serve in various functions even if it does not code for functional RNA.
It will be fun to read how Wells deals with the issue of spurious transcription based on his understanding of how RNA polymerase and transcriptional activators bind to DNA. I'm certainly looking forward to learning about the reliability of those genome studies on transcription and I'm sure Wells is going to discuss conflicting data in the scientific literature. After all, Wells has a Ph.D. in molecular biology so he must know about the real scientific controversy, right?

As for functions that don't require transcription, I highly recommend my short summary of these in What's in Your Genome. We've known about them for decades but apparently the IDiots think this is a new discovery.
So far, the Darwinist response fails to appreciate that Jonathan is in the act of very seriously blunting a Darwinian icon. What, in this context, is an icon? It's a mainstay in the public debate about Darwinian evolution that turns out, on inspection, to be based not on solid science but on puffery, illusion or deception.

This is another icon that, as Jonathan shows, was in the process of being blunted by biologists who are not ID advocates, well before Dr. Wells gathered the evidence together so concisely and conveniently in these pages.
Whatever. Wells' first book, Icons of Evolution was full of lies and I suspect this one will be too. Only one of the ten so-called icons was "blunted" by Wells and that one was the Haeckel drawings. Even then, Wells seriously distorted the significance of those fake drawings by claiming that there was now no evidence of similarities in the development of all mammals.

Friday, May 13, 2011


Today is Friday the 13th. It's also my birthday! I was born in 1946. Do the math.

I have no plans to retire 'cause I'm having too much fun.

Sunday, May 08, 2011

What's in Your Genome?

The total size of the human genome is estimated to be 3.2 × 109 bp [How Big Is the Human Genome?]. Here are the major components.

Transposable Elements: (44% junk)

   DNA transposons:
  • active (functional): <0.1%

  • defective (nonfunctional): 3%

  • active (functional):<0.1%

  • defective transposons
                (full-length, nonfunctional): 8%
                L1 LINES (fragments, nonfunctional): 16%
                other LINES: 4%
                SINES (small pseudogene fragments): 13%

  • co-opted transposons/fragments: <0.1% a
    aCo-opted transposons and transposon fragments are those that have secondarily acquired a new function.

Viruses (9% junk)

   DNA viruses
  • active (functional): <0.1%

  • defective DNA viruses: ~1%

   RNA viruses
  • active (functional): <0.1%

  • defective (nonfunctional): 8%

  • co-opted RNA viruses: <0.1% b
    bCo-opted RNA viruses are defective integrated virus genomes that have secondarily acquired a new function.

Pseudogenes (1.2% junk)
  • (from protein-encoding genes): 1.2% junk
  • co-opted pseudogenes: <0.1% c
    cCo-opted pseudogenes are formerly defective pseudogenes those that have secondarily acquired a new function.
Ribosomal RNA genes:
  • essential 0.22%
  • junk 0.19%
Other RNA encoding genes
  • tRNA genes: <0.1% (essential)

  • known small RNA genes: <0.1% (essential)

  • putative regulatory RNAs: ~2% (essential)

Protein-encoding genes: (9.6% junk)
  • transcribed region:
                essential 1.8%
                intron junk (not included above) 9.6% d
    dIntrons sequences account for about 30% of the genome. Most of these sequences qualify as junk but they are littered with defective transposable elements that are already included in the calculation of junk DNA.
Regulatory sequences:
  • essential 0.6%
Origins of DNA replication
  • <0.1% (essential)

Scaffold attachment regions (SARS)
  • <0.1% (essential)

Highly Repetitive DNA (2% junk)
  • α-satellite DNA (centromeres)
    • essential 1.0%
    • non-essential 2.0%
  • telomeres
    • essential (less than 1000 kb, insignificant)
Intergenic DNA (not included above)
  • conserved 2% (essential)
  • non-conserved 26.3% (unknown but probably junk)
Theme Genomes & Junk DNATotal Essential/Functional (so far) = 7.7% Total Junk (so far) = 65% Unknown (probably mostly junk) = 27.3%
For references and further information click on the "Genomes & Junk DNA" link in the box
LAST UPDATES: May 10, 2011 (fixed totals, and ribosomal RNA calculations)
June 3, 2011 (added total genome size)
February 5, 2013 (reformatted)