Protein evolution – Two responses

Recently an article was published about protein evolution in the prestigious journal Nature. It showed that a combination of two mutations is enough to switch the binding specificity of  that particular protein to another class of binding ligands.

For this study, McLaughlin et al. used a small peptide and mutated every amino acid in this peptide to create 1578 variants of the original protein. All those proteins were checked for binding to the normal binding partner of this protein (PSD95pdz3). The results are that substitutions on 75% of the sites did not have any influence on protein function, but they showed that two coordinated mutations are needed to effectively change the binding partner of this protein. In fact, they showed that although two muations are needed, that there was also an intermediate, which did bind to both binding partners.

Mutational gain or loss of function at each position of protein relative to wild type protein (red:gain;blue:loss;) Taken from McLaughlin et al. 2012

The implications of this study are profound for the way we thought that proteins evolve. It confirms the prediction that most of the mutations have little effect on a protein and proteins are in fact really resilient to change.

The Intelligent Design community claims that mutations are really bad for someone, and that proteins are ruined most of the time when a mutation occurs. But this study shows that – although for one protein – this is not the case. Furthermore this shows that proteins in theory can evolve a new function, which is in absolute disagreement with the predictions of Intelligent Design. Creationist Todd Wood already pointed this out several weeks ago on his blog.

But he also pointed out the implications for creation science. His conclusion was the following:

As for me, I’ve always thought that the resilience of proteins to mutations spoke well of their original design.  Proteins are not incredibly sensitive to mutation, breaking down the minute one mutation happened.  That would be a terrible design.  Instead, they’re built to last, which is what I would expect from a wise designer.

And I agree completely with that!

But of course not everybody. An article that was written by Dr. Tompkins at the ICR  disagrees. In fact, they think that this study shows that protein cannot really evolve new functions. What they say is the following:

Data from similar, but less extensive, studies prior to this one show that random mutations in even the simplest of bacterial proteins have impossible hurdles to overcome if they are to create new function, even if it only happens one amino acid at a time. It also showed how key sectors of proteins are so tightly designed that they tolerate virtually no change whatsoever.

If you read the study of McLaughlin carefully you will immediately see that they say that proteins are sensitive to mutations in particular regions and that proteins are also insensitive in other regions. At the ICR they see this as a confirmation that proteins cannot evolve.

The article states that most of the amino acid positions the protein is not sensitive to mutations. They show that only 20 out of 83 amino acids do not tolerate mutations.

Most positions show little effect on mutation, tolerating nearly every substitution even if radically different in chemical character (Fig. 2a–c and Supplementary Fig. 5). This  includes some that are in direct contact with peptide ligand (for example, 326 and 380), and some that are buried in the protein core and largely conserved (for example, 314, 316, 356, 357 and 390). By contrast, a subset of positions (20 out of 83, Fig. 2c) shows significant sensitivity to mutation (.2s from mean). Within the binding pocket, His 372 tolerates essentially no other substitution and Leu 323, Phe 325, Ile 327, and Leu 379 show tolerance to only the most chemically conservative mutations

That gives some credit to the claim that they make at the ICR. But they forget to mention that they also did a mutational study in which they changed the binding partner of the protein to another. Only two coordinated mutations are needed. And moreover, they show that they found an intermediate that has binding affinity for both binding partners. That means new function (or change in function)

At the ICR they cite Douglas Axe, who showed that amino acids that are used to make binding site for a protein, and thus have a direct influence on function, are extremely sensitive to mutation. That’s true, but this study shows that  protein evolution could happen.

Unfortunately for evolutionary concepts, these sectors are exactly where nature would need mutations to occur in order for it to construct new cellular interactions that might contribute to a new, selectable trait.

Wait a moment! If evolution should have a mutation in these sectors, why did they found a protein that has an intermediate binding specificity and a protein in which the binding partners were switched? I would call that an example of protein evolution in action. 

Imagine if this sort of experiment was done in more complex proteins that are hundreds of amino acids in length, or protein complexes that also include metal ions, carbohydrates, and ribo-nucleotides integrated into their structures.

And why should that be else for other (bigger) proteins. We know that substitutions are most of the time neutral? Or nearly neutral. But this finding is more likely holding up for bigger proteins.

It is interesting to view the interpretation of two young-earth creationists. But what shame is there for creationist to admit that God created a robust creation, which precisely is in accordance with the view that mutations are not always ruining protein function? Also the respons from the ICR shows that they are heavily influenced by the intelligent design movement, and it remains to be seen whether that is the right track…

McLaughlin et al. 2012. The spatial architecture of protein function and adaptationNature10.1038/nature11500 

Any thoughts?

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3 thoughts on “Protein evolution – Two responses

  1. I think the idea that the genome was designed to be static is a holdover assumption from a generation or so ago. If you are familiar with physiology, we were certainly not designed to remain static. Is there a valid creationist reason to believe the genome should be static? Most creationists who spend a lot of time with apologetics tend to assume yes. Many mutations have been shown to be harmful, therefore it is easy to believe that all of them are. There has been a bias this way about other things in the past (viruses, bacteria) since disease research gets funding. Creationists can point to the fact that at creation God called everything very good, and some find it easy to believe all mutations are a corruption of a perfect design. I have been convinced for some time that some degree of protein evolution is part of the robust design of God’s creatures. He told them to reproduce and fill the earth. I believe some degree of genetic change has been required for this to happen. So when I look at mutations I believe I see two things: 1) degeneration as a result of the Curse, and 2) God’s provision for His creatures even in a fallen world. To me, that is a much more biblical thing to expect.

  2. Is it really protein evolution being shown or simply protein front-loading being tested in a lab? To me it is the latter as evolution is about novel functionality. Proteins seem to have always had the ability to tolerate mutations.

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