Thursday, November 4, 2010

My Response To Dryden et al.

The science journals appear to have come up with a clever strategy to keep papers critical of Darwinian evolution out of the peer-reviewed literature: simply reject the papers or letters to the editor on the grounds that "your response would not be of interest to our readers.” This is evidenced by the refusal to publish Michael Behe's responses to various papers. In short: if you're critical of a paper that attempts to explain a problem for Darwinian evolution, then your paper is not interesting, and hence it won't be published. It's a neat trick, and one that I suspect I fell for.

         First off, I submitted a manuscript to the Journal of the Royal Society Interface. My paper was a critique of a paper by Dryden et al. 2008, "How much of protein sequence space has been explored by life on Earth?" In this paper, Dryden et al. argue that by reducing the functional amino acid repertoire, to, among others, a binary amino acid alphabet consisting of hydrophobic and hydrophilic amino acids, then evolutionary processes can easily navigate the whole of functional protein sequence space. Consider that for a protein only 100 amino acids in length, there are 20^100 potential amino acid combinations. By reducing the functional amino acid alphabet to one consisting of only hydrophobic and hydrophilic amino acids, then protein sequence space has a potential of only 2^100 functional sequences. Essentially, they argue that the only thing that matters for a protein to function is that the protein has the right sequence arrangement of hydrophobic and hydrophilic residues. They try to reduce the amino acid repertoire through other means, but the point is this: the paper is nonsense. There are many glaring errors in that paper, some of which I point out in the response I submitted to the Journal of the Royal Society Interface (I submitted the manuscript on August 28, 2010).
Well, gee, but ten days later I received the journal's decision regarding my paper. It shouldn't be hard to guess why they rejected my paper.
Here's a hint: it's not because the reviewers sent a rebuttal to my paper, and it's not because my paper made some error in biology.

So, anyway, here's why they rejected my paper:

"Thank you for submitting your manuscript entitled "On the Reduction of the Amino Acid Repertoire in Functional Protein Structures" to J. R. Soc. Interface.

...Many more good manuscripts are submitted to us than we have space to publish, and we give preference to those that present significant advances of broad interest. Unfortunately, your manuscript has been rejected at this stage, as it was not considered to have sufficient appeal for the general readership of J. R. Soc. Interface."  [emphasis added]

Okay, I'll admit that my paper did not represent any real experimental research. But interestingly enough, Dryden et al.'s paper wasn't an experimental paper either, but purely theoretical. However, since I guess it had sufficient appeal for the general readership of the journal, it got published. No problem.

Oh, and I forgot to include this last line the journal sent me:
"Thank you for your paper and I hope that it will be published elsewhere." That makes me feel better.

   Now for those of you interested in my critique of Dryden et al.'s paper, I will link to my response at the end of this post (too bad, but my paper didn't refer to some fairly recent work that further supports my paper).

Here's the abstract:


It has been postulated by Dryden et al. [Dryden David T.F, Thomson Andrew R, White John H. How much of protein sequence space has been explored by life on Earth? J. R. Soc. Interface, 5,25:953-956 (2008)] that the amino acid repertoire of functional protein structures may be reduced to a binary one consisting of hydrophobic and hydrophilic residues without affecting protein function. Moreover, they point to proteins with a low degree of functional complexity and posit that such structures demonstrate that the actual identity of most of the amino acids in a protein is irrelevant. They conclude that, as a result of such reduction there is no role for molecular contingency, and furthermore that potential functional protein sequence space is completely explorable.
        Here, based on presented data and through a protein sequence alignment, it is shown that the stated postulate does not hold. For this reason, I conclude that there is a role for molecular contingency and not all of functional protein sequence space has been explored by life on earth.

Here's the full paper:

And finally, here are all the beta-tubulin sequences I aligned from 30 different organisms (that took quite a toll on my hands):

Now I have to go and revise a paper that I'm having a little better luck with. And I have to go eat a sandwich because I actually am not a robot behind a computer screen, contrary to popular opinion.

The finishing touch to this will be two quotes from two different Darwinians:

" the molecular level, there is no role for contingency."
-Dryden et al. 2008, "How much of protein sequence space has been explored by life on Earth?"

"... historical contingency is especially important when it facilitates the evolution of key innovations that are not easily evolved by gradual, cumulative selection."

-Blount ZD, Borland CZ, Lenski RE (2008) Historical contingency and the evolution of a key innovation in an experimental population of Escherichia coli. Proc Natl Acad Sci U S A 105(23):7899-7906.


In my paper, one of the conserved residues in beta-tubulin is cys-12. Since this residue is conserved in all thirty organisms, one would predict that this residue is critical to beta-tubulin function. This prediction is confirmed by site-directed mutagenesis of this residue by Gupta et al. 2001:
"The results suggest that the C12 and C354 residues play important roles in the structure and function of tubulin."

Gupta ML, et al. Mutagenesis of beta-tubulin cysteine residues in Saccharomyces cerevisiae: mutation of cysteine 354 results in cold-stable microtubules. Cell Motil. Cytoskeleton, 49(2):67-77 (2001).

1 comment:

  1. If the above links do not work, please do not hesitate to inform me.