Wednesday, April 13, 2011

Protein evolution in BIO-Complexity

I've been asked by one of my readers to comment on the latest paper published in BIO-Complexity. Longsuffering readers of my blog will recall that BIO-Complexity is an online, open access journal that "aims to be the leading forum for testing the scientific merit of the claim that intelligent design (ID) is a credible explanation for life." I mentioned this journal previously with my final comment being:
I see BIO-Complexity as a positive response to the challenge of put up or shut up, and that's good. I hope it will go beyond just anti-evolution rhetoric research, but I guess that remains to be seen.
Some thought I was just being snarky, but I meant that. I think the ID movement has become far too associated with (appropriated by?) populist anti-evolutionism. I think that's not so good if you really want to offer a genuine alternative model to the evolutionary model of origins. The launch of Biologic, insofar as it offers a home for genuine research, was good, and the launch of a journal dedicated to publishing the sort of research that Biologic generates is also good.

So that leads me to the latest paper in BIO-Complexity, The Evolutionary Accessibility of New Enzyme Functions: A Case Study from the Biotin Pathway by Gauger and Axe. If you don't want to wade through the paper, here's a quick breakdown: Paralogous enzymes are presumed to share a common ancestor, even though they have different functions. The common ancestry of paralogous enzymes is inferred from their significant sequence and structural similarity. Gauger and Axe try to introduce directed mutations into one enzyme in order to convert its function into that of a paralogous enzyme. This is ostensibly a test of the feasibility of mutation and selection to produce novel functions from duplicated genes (the putative source of paralogous enzymes). Obviously, there's a lot more detail than that, but you can read that for yourself in their paper.

Having read the paper, I'm left with a lot of questions. To be honest, I'm confused. The introduction clearly laid out the goal of the paper as testing the feasibility of something called "neofunctionalization" (a word that they don't actually use). Neofunctionalization is the development of a truly new function after gene duplication. So after I read the introduction to the paper, I expected a certain type of evolutionary methodology, but that's not the style of method they used. Instead, Gauger and Axe approached the issue as a practical biochemist would: If we have two paralogous enzymes, can we interchange enough amino acids to make one function like the other? That's definitely a topic of great interest to biochemists. How does the sequence and structure of an enzyme relate to its function? But it's not exactly the way an evolutionary biologist would go about addressing the question of neofunctionalization.

If I were addressing this research problem, the first thing I would do is create a phylogeny of the enzymes in question and start trying to reconstruct putative ancestral sequences. Ancestral sequence reconstruction is an active area of research in evolutionary biochemistry (see Google Scholar), so there's plenty of precedent and methods available. This would provide me with the "best case" for the evolution of these enzymes for my evaluation. I could synthesize the putative ancestral proteins and begin studying their function, or at the very least, I could infer some likely mutational pathways that must have been taken if the enzymes had evolved.

Instead of ancestral reconstruction, Gauger and Axe focused directly on converting an existing enzyme into another existing enzyme. That left me scratching my head, since no evolutionary biologist would propose that an extant enzyme evolved directly into another extant enzyme. So they're testing a model that no one would take seriously? Hmmm...

That's not at all to say that the research was bogus or unhelpful. Quite the contrary, their work contributes yet more data to the ongoing research area of structure/function relationship. As most biochemists have found, that relationship is really complicated. I'm just not sure that this particular study has much evolutionary application, due to its non-evolutionary methodology.

In the larger scheme of things, I am sensing a discouraging pattern to BIO-Complexity publications. As I quoted above, the journal is supposed to be about "testing the scientific merit of the claim that intelligent design (ID) is a credible explanation for life," which is a great goal. But this is the fifth paper published by BIO-Complexity, and it's the fifth paper that focuses on perceived inadequacies of evolution. So when are we going to test "the scientific merit of the claim that intelligent design (ID) is a credible explanation for life?"

I don't want to be too pessimistic, though, since I am a big fan of research and technical publications. I'm genuinely happy that BIO-Complexity exists and is publishing this sort of work. I just hope that in the future, we'll begin to see some positive research for ID rather than just anti-evolution work.

Gauger and Axe. 2011. The Evolutionary Accessibility of New Enzyme Functions: A Case Study from the Biotin Pathway. BIO-Complexity 2011:1-17.

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