Another example of “scholarship”

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With the recent resounding defeat of Intelligent Design in Dover, ID supporters may actually have to try and do some science to support their claims. On the basis of past efforts, the prospect does not look good for them. Richard von Sternberg, the Intelligent Design-friendly editor who was responsible for publishing Meyer’s woeful review paper, has recently had a paper published with anti-Darwinian James Shapiro (who has said he is not an ID supporter).

Shapiro JA, von Sternberg R. Why repetitive DNA is essential to genome function. Biol Rev Camb Philos Soc. 2005 May;80(2):227-50.

In this they try to address the bete noir of creationists, both young earth and intelligent design varieties, “Junk” DNA. The fact that the vast majority of the genome is probably parasitic junk is hard to reconcile with an intelligent designer, so a lot of effort is expended to show that all that DNA must be doing something essential. Sternberg and Shapiro try to show that one major class of non-coding DNA, highly repetitive DNA, is essential for genome function. However, all they end up demonstrating is shoddy scholarship.

One of the fruits of the genomic revolution is the finding that the majority of most eukaryote genomes don’t code for proteins. In humans, only around 1-2% of our DNA codes for proteins. The remainder consists of genes for ribosomal RNA, small regulatory RNAs of various types, regulatory elements, broken genes (including defunct viral genes incorporated into our DNA), the spacers that exist within genes, a whole lot of intergene material and lots of repetitive sequences. The regulatory elements (stretches of DNA where proteins can bind to change gene expression, stretches of DNA that code for small RNA’s that can modify gene expression etc.) are critical for co-ordinating gene expression during development and during adulthood. We need these as much as we need protein coding genes, but overall it is broadly estimated that that only about 3-5% of the non-coding genome is involved in regulation (Mouse Genome Sequencing Consortium, 2002). So what is the rest doing?

GENOME.jpg

Overall, not a lot. The general consensus is that the majority of the non-coding, non-regulatory DNA is functionless (the so called “junk DNA”). Some might have a strictly structural role (where you need x bases of DNA, any kind of DNA, to support the structure of the chromosome, this role is sequence independent), but overall the vast bulk of DNA is without function. There are a number of reasons to believe this, but I will talk about some of this evidence later. Roughly 50% of DNA is what is called repetitive DNA, a sort of molecular stutter. In general (but there are exceptions), a large proportion of this is seen as “selfish” or “parasitic” DNA. The majority of this repetitive DNA is made up of transposable elements. Long interspersed elements (LINES) make up 21% of the human genome, and some code for genes that allow them to make copies of themselves. Short interspersed elements (SINES) make up about 11% of human DNA and require active LINES in order to be copied. Now, it is almost certain that a small proportion of LINES and SINES has been co-opted to do something useful in the genome, about 0.1% of SINES may be involved in alternative splicing of genes. However, as it currently stands the vast majority of these elements don’t seem to do anything useful.

Now, as I said, there are a number of reasons why biologists think that the majority of non-coding DNA is non-functional. However, the idea that the bulk of the genome does nothing is seriously worrying to Young Earth and Intelligent Design creationists. The paper by Shapiro and von Sternberg tries to claim that the repetitive DNA in our genomes is essential. It consists of large amounts of hand waving, some out-of-context quotation and trying to shoehorn the expression of the genome into a computer file metaphor. I won’t go into the entire paper in detail, but I will look at one example that demonstrates the shoddiness of the “scholarship” in this paper.

One of the challenges to the idea that the majority of non-coding DNA is doing something useful is the existence of organisms like the puffer fish Fugu. Despite being a fairly complex vertebrate, with roughly similar number of genes to humans, it has between half to one-third the non-coding DNA that other vertebrates (and non-vertebrates) have. So what do Shapiro and von Sternberg say about Fugu? Their only mention is this:

“Rapidly reproducing organisms, like Caenorhabditis, Drosophila, Fugu and Arabidopsis, tend to have stripped-down genomes with relatively less abundant repetitive DNA, while organisms with longer life cycles, such as humans and maize, have larger genomes with correspondingly more repetitive elements (Table 1).”

However, their own table shows that this is nonsense.

In order of reproductive rate

Organism % Genome repetitive DNA Reproduction rate
Caenorhabditis briggsae 22% approx 25-50 times per year
Drosophila (fuit fly) 34-57%* 6-12 times per year
Clionia(tunicate) 35% several times to once per year
Mouse 40% 3-4 times a year
Fugu 15% Once per year
Dog 31% Once per year+

* In male Drosophila the Y chomosome is mostly repetitive DNA. + Some dogs can potentially reproduce twice a year. Clionia reproduction can range from continuos release of spawn to once per year, depending on latitude. Fugu has a broad spawing period of about 2 months, but it takes about a year to go from from fertilization to sexual maturity. Fugu has less repetitive DNA than the microscopic worm Caenorhabditis briggsae, which reproduces every week.

As you can see, from their own table (I’ve added in the reproduction rates to make this clear) the amount of repetitive DNA is not correlated with reproduction rate. I’ve actually done the statistics on this. You can look at either time to reproductive maturity, or interval between successive broods, but either way there is no correlation between amount of repetitive DNA and reproduction ate (P > 0.1 and 0.3 respectively).

Repetiviive_DNA1.jpg

In bacteria, there is very little repetitive DNA, this is thought to be due to their fast reproduction rate (hours to days). But Fugu reproduces relatively slowly, certainly slower than mice and Drosophila, yet it has far less repetitive DNA than them. The upshot is that Fugu, a reasonably complex vertebrate with about as many protein coding genes as humans, and more than Drosophila, gets by with half to one third of the repetitive DNA most complex metazoans have, suggesting these sequences are not essential. However, Shapiro and von Sternberg hand wave the Fugu data away with that single, brief, and above all incorrect statement quoted above

The Fugu data is not the only evidence that most non-coding DNA is functionless. To start with the single celled amoeba has a genome 200 times larger than the human genome, most of it repetitive DNA. It would be hard to argue that the amoeba needs far more repetitive DNA than humans to organise its genome.

Furthermore, we have evidence from sequence conservation. If the repetitive DNA has a function, then its sequence should be conserved (for example if it serves as binding sites for regulatory proteins). However, the majority of the repetitive DNA is not conserved. Indeed, Kimura famously predicted that humans should have around about 1% protein coding genes based on mutation patterns (Kimura and Ohta, 1971). We actually have roughly 1-2% of our genome coding for protein (Nusbaum et al 2005). The sequence conservation data is compatible with over 90% of our genome doing not very much at all (either as regulatory sequences or protein coding sequences). Now, about 3-5% of repetitive DNA is conserved, which suggests that it might do something (Nobrega et al, 2004; Nusbaum et al 2005). So, what happens when this conserved repetitive DNA is removed?

The answer is “beggar all”. In a recent paper (Nobrega et al, 2004) megabase sections of non-coding DNA, including many conserved repetitive sequences, were deleted from the mouse genome. Nothing happened to the mice, they were perfectly normal. Of course something subtle might be wrong, but deleting a megabase of coding DNA gets you one dead organism, so this non-coding DNA can’t be as important as Shapiro and von Sternberg say. This data supports earlier experiments where smaller amounts of non-coding DNA were removed. Also, there are natural human mutants where large chunks of non-coding DNA containing conserved repetitive elements go AWOL with no effect (Sebat et al, 2004). Shapiro and von Sternberg don’t mention the Nobrega paper or this other evidence at all.

So, overall there is strong evidence that most of the non-coding DNA in complex metazoans is not functional (some might be purely structural scaffolding though). Around 3-5% of non-coding DNA is likely to be involved in regulation of gene activity, and some small percentage of non-coding repetitive elements may have some regulatory function, but even with the most generous estimates (which the Nobrega et al paper suggests are over estimates) at least 90% of the human (and other vertebrate) genome is doing nothing functionally important. Shapiro and von Sternberg don’t address these important findings, which says a lot for ID scholarship (or lack thereof).

References

  • Kimura M and Ohta T (1971), Theoretic Aspects of Population Genetics, Princeton University Press, p28.
  • Mouse Genome Sequencing Consortium. (2002) Initial sequencing and comparative analysis of the mouse genome. Nature 420, 520–562.
  • Nobrega MA, Zhu Y, Plajzer-Frick I, Afzal V, Rubin EM. (2004) Megabase deletions of gene deserts result in viable mice. Nature. 431(7011):988-93.
  • Nusbaum C, et al., (2005) DNA sequence and analysis of human chromosome 18. Nature 437, 551-555
  • Sebat, J. et al. (2004) Large-scale copy number polymorphism in the human genome. Science 305, 525–528

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Lingering Questions re Sternberg from Get Busy Livin', Or Get Busy Bloggin' on December 23, 2005 7:18 AM

I want to present a positive spin on the Sternberg saga by offering some questions, which, when answered, will likely evaporate much of the lingering air of malfeasance. I think that if Sternberg really feels he is still being viewed as a "heretic", ... Read More

20 Comments

Ian, are you going to consider submitting this (or an extended critique) to the journal? Does it accept such submissions?

Wait, this was published in a scientific journal? Which one? Any word from the editors?

Fill us in on the non-Darwinian non-ID thoughts of JA Shapiro.

(For a confused moment, I wondered whether this was the Shapiro of “Origins” fame; but that’s Robert Shapiro.)

So do we have any idea why Fugu has such an abbreviated genetic code? I feel like I’m reading a cliffhanger here :P

Sternberg has published a few things in the literature critical of ‘darwinism’ (despite claiming that you can’t do so, i.e. lying). Also, this wouldn’t be the first paper arguing for a function for some junk DNA (the others from regular evolutionary scientists), but they seem to be bumping the claim up a tad.

The journal (see Ian’s reference) is not one that I’ve heard of (though I’m a geologist not a biologist) and I’d guess is relatively minor.

The journal is significant enough our university library has a subscription. (I just downloaded the article in question.)

Also, Shapiro cited this article (in press) in this review:

“A 21st century view of evolution: genome system architecture, repetitive DNA, and natural genetic engineering” Gene 345:91-100 (January, 2005)

SteveF Wrote:

Ian, are you going to consider submitting this (or an extended critique) to the journal? Does it accept such submissions?

I don’t know. I’l have to look in to it when I am a bit less busy.

Maybe I’m wrong, but I didn’t see anything here about non-coding genome segments reducing the risk of destructive crossover, which would not affect an individual organism, but would affect it’s offspring and would therefore be selected-for. This is easy to see in GP simulations and almost always happens with a variable length genome (it’s also known as “intron bloat”).

So do we have any idea why Fugu has such an abbreviated genetic code? I feel like I’m reading a cliffhanger here :P

The key to the puzzle of widely varying DNA amounts in organisms (the “c-value”) is that c-value correlates quite tightly with cell volume. Organisms with small cells (typically rapid-developing creatures) have small c-values.

I was under the impression that the differences in c-value are due to differences in the amount of repetitive DNA, but Ian’s table seems to contradict that (but it is a limited sample of genomes).

See the Junk DNA page at EvoWiki for a little more on this.

While generation time effects probably don’t affect the size of a genome (they do affect the rate of neutral evolution), population size can affect the size of the genome. Because the strength of selection depends on both fitness effects and population size, selection against insertions of repetitive DNA will be stronger in smaller populations. This theoretical framework (laid out by Lynch and Connery) was supported by a recent study of ray finned fishes.

As for the relevance of the journal, I have never heard of it and I study molecular evolution. If this paper was anything near decent it would have been published in Genome Research, Molecular Biology and Evolution, the Journal of Molecular Evolution, or some other journal in this field.

Sorry, the post above should say selection against insertions will be stronger in LARGER populations. Small populations should have larger genomes, and this is supported in a study of ray finned fishes.

Slightly off-topic question from a non-biologist: I’ve heard that chimps and humans share something like 95% of our DNA, does this number refer to the whole DNA, or just the functional DNA?

I have made a 35-page peer-reviewed .PDF of Sternberg’s criticisms of Darwinism, a paper to the Annals of the NYAS, available on my website. Remember that copyright laws apply.

Curious they mention maize as having a long life cycle. The life cycle is just as long as rice, which has sod-all junk DNA. That’s why rice was used as the model cereal for sequencing. Clearly there’s no reason to expect a huge difference in complexity between rice and the other cereals (wheat, barley etc. also have a lot of junk).

Oh, and the journal can’t be that bad: Gould published a paper in it. In 1966.

Bob

P.S. A couple of smnall statistical gripes: 1. the 3D pie chart is naughty: the amount of protein encoding DNA is distorted so that it looks less than it actually is. 2. Never mind the p-value, what about the R^2? To me there seems to be a positive correlation, but I’d like to see more data. And more data would tend to reduce the p-value, so you can always make the relationship significant, just by adding more data.

Bob you can’t evaluate an r2 value from a regression analysis until the model is considered a significant representation of the data, evaluated via a p-value. If you take and run only a correlational test on it the correlation coefficient is extremely low, so you really aren’t explaining any of the variation in DNA length by using reproductive rates.

Scott Reese Wrote:

Bob you can’t evaluate an r2 value from a regression analysis until the model is considered a significant representation of the data, evaluated via a p-value.

Which biologist did you learn this from? It simply wrong. You can get a decent R^2 but not one that is significant simply by having a small data set. Conversely, you can get a significant regression with an R^2 of only a few percent, but having a large data set (I’ve managed a significant p-value with R^2=4%). p-values are evil: they’re not measures of effect size.

Sorry, you’ve stumbled on to one of my bête noirs. I’m a professional statistician, and this worship of p-values really annoys me (and others in my profession). I also guess this means I should take a break…

Bob

“The general consensus is that the majority of the non-coding, non-regulatory DNA is functionless (the so called ‘junk DNA’).”

So, am I correct in understanding that “Evolutionary Theory” predicts that this “so-called ‘junk DNA’” is really “junk”? If it turns out that later this “so-called ‘junk DNA’” is found to have a function (or, at least, a high percentage of it), would that constitute a falsification of “Evolutionary Theory”, and a vindication of ID, or perhaps (oh, the horror) of Creationism? If not, then isn’t it silly to argue that “so-called ‘junk DNA’” supports “Evolutionary Theory” and undermines ID (and/or Creationism)?

So, am I correct in understanding that “Evolutionary Theory” predicts that this “so-called ‘junk DNA’” is really “junk”?

Nope, you are not correct.

If it turns out that later this “so-called ‘junk DNA’” is found to have a function (or, at least, a high percentage of it), would that constitute a falsification of “Evolutionary Theory”, and a vindication of ID, or perhaps (oh, the horror) of Creationism?

Nope, it would not. And even if evolution were conclusively shown to be one thousand percent wrong on every possible point, that still doesn’t make ID right by default.

If not, then isn’t it silly to argue that “so-called ‘junk DNA’” supports “Evolutionary Theory” and undermines ID (and/or Creationism)?

Um, no one is arguing that. Except IDers. And we already know that they are full of it. (shrug)

Pepeloco Wrote:

Slightly off-topic question from a non-biologist: I’ve heard that chimps and humans share something like 95% of our DNA, does this number refer to the whole DNA, or just the functional DNA?

Slightly off-topic answer from an evolutionary genomicist ;) Of the regions of their genomes that can be identified as being the same, 98.94% of nucleotides are identical between humans and chimps [Mikkelsen et al. (2005) Nature]. This is the figure often used by the media to give the impression that we’re extremely similar at the genetic level. While this reflects the “whole DNA” (not just the functional parts), bear in mind that there are large chunks that are unique to one or the other species. At the genomic level, humans and chimps are probably between 90-95% identical.

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This page contains a single entry by Ian Musgrave published on December 22, 2005 8:19 PM.

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