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Molecular Clues of Teleology

January 12, 2012

Molecular Clues of Teleology

Previously, I mentioned a testable prediction the front-loading hypothesis makes. I said that:

Importantly, the front-loading hypothesis predicts that these homologs of protein components in important molecular machines will be more conserved in sequence identity than the average prokaryotic protein.” (Consider reading my previous post so that this post might be more intelligible.)

Well, I decided to tentatively test this prediction made by the front-loading hypothesis, using a small dataset consisting of only two important eukaryotic proteins: tubulin and actin. The former protein consists of more than one chain, so I only focused on the beta chain.

Here’s the deal:  both of these proteins are well-conserved among eukaryotes. They play a crucial role in eukaryotes, as well. Tubulin is a major component of cilia, and actin can be found in sarcomeres, an important component of muscle cells. Actin also plays a major role in the cytoskeleton.

Tubulin shares homology with a prokaryotic protein, FtsZ, while actin shares homology with the bacterial protein MreB.

To test the prediction I outlined earlier, we need to align tubulin, actin, FtsZ, and MreB amino acid sequences to determine the degree of sequence conservation for each protein.  So, I grabbed a couple of tubulin beta sequences from UniProt, one belonging to Volvox  (accession number: P11482) and the other to a frog (Q91575). When aligned (using ClustalW), there is 88.514% sequence identity shared between the two sequences. The same procedure was done for actin: a Volvox actin sequence (P20904) was aligned with a frog actin sequence (P04751). The result was 89.655% sequence identity shared between the two sequences. Clearly, both tubulin and actin are very highly conserved in sequence identity, with actin being just slightly more conserved.

What about the prokaryotic homologs of these two proteins? Are they also well-conserved, as is expected under the front-loading hypothesis, or are they no more conserved than the average prokaryotic protein?

When FtsZ sequences belonging to Escherichia coli (P0A9A6) and Caulobacter (P0CAU9) are aligned, there is 83.3% sequence similarity.  The most common degree of sequence similarity between E. coli proteins and Caulobacter proteins ranges from 51-60% sequence similarity. Thus, the fact that tubulin’s prokaryotic homolog is considerably more conserved in sequence identity than the average prokaryotic protein is exactly what we would expect under the front-loading hypothesis.

I did the same thing with actin’s prokaryotic homolog, MreB. If we align MreB sequences from E. coli (P0A9X4) and Caulobacter (Q9A821), there is 86.5% sequence similarity. Interestingly enough, the telic prediction plays out again.

But this isn’t the whole story. Recall that I also noted in my previous post that: “…the front-loading hypothesis predicts that, in general, the more highly conserved in sequence identity a protein component is in a [major eukaryotic molecular system], then the higher the degree of sequence conservation will be in its prokaryotic homolog…

And this is exactly what we find for FtsZ and MreB. In eukaryotes, actin is slightly more conserved than tubulin, suggesting that actin is just a bit more important than tubulin. Consistent with the front-loading prediction, we find that actin’s prokaryotic homolog, MreB, is more conserved than tubulin’s prokaryotic homolog, FtsZ. This correlation is expressed in the figure below.

Figure. This illustrates the observation that actin is more conserved than tubulin, and interestingly, actin’s prokaryotic homolog, MreB, is more conserved than tubulin’s prokaryotic homolog, FtsZ, which is what the front-loading hypothesis predicts. Cool!

Thus, we can see that the two predictions I made earlier, from a front-loading perspective, are tentatively confirmed, tantalizing us to explore this further with larger data sets. Since only a small dataset was used here, the predictions can only be considered very tentatively confirmed. But it’s a clue that teleology was involved in life’s history.

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